Abstract
This study explores the application of serum biomarkers in the diagnosis of adenomatous polyps and evaluates the effectiveness of different markers and their combined diagnosis in adenomatous polyp detection. Using receiver operating characteristic curve analysis, this study assessed the efficacy of serum biomarkers such as carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), alpha-fetoprotein (AFP), carbohydrate antigen 199 (CA199), and prothrombin time (PT) in diagnosing adenomatous polyps in 90 patients. The study also compared the diagnostic accuracy of individual tests versus combined diagnostic approaches and analyzed the impact of polyp size and number on the levels of these markers. Among the individual tests, CA125 showed relatively high diagnostic efficacy. However, combined diagnostic approaches, such as the combination of CEA and CA125, the trio of CEA, CA125, and AFP, and the quartet of CEA, CA125, AFP, and PT, significantly improved diagnostic sensitivity and specificity. Additionally, the study found that the size and number of adenomatous polyps significantly influenced the levels of CEA, CA125, CA199, and PT, with larger and more numerous polyps associated with higher marker levels. This study demonstrates that combined diagnostic strategies have significant advantages in diagnosing adenomatous polyps, providing more accurate and comprehensive diagnostic information. Furthermore, the impact of polyp size and number on serum biomarker levels suggests that these clinical factors should be considered in clinical assessments. These findings offer new perspectives and approaches for the diagnosis of adenomatous polyps.
Keywords: adenomatous polyps, AFP, CA125, CEA, combined diagnosis, PT, serum biomarkers
1. Introduction
With the acceleration of population aging and the advancement of medical research, the health issues of elderly men are receiving increasing attention.[1,2] Among elderly men, gastrointestinal polyps are a common benign condition, and their incidence rises with age. Although most gastrointestinal polyps are benign, adenomatous polyps are of particular clinical concern due to their potential risk of malignant transformation. The malignancy of adenomatous polyps not only affects the quality of life of patients but also poses a life-threatening risk.[3] Therefore, early detection, diagnosis, and treatment of adenomatous gastrointestinal polyps in elderly men are of significant clinical and social importance.
Diagnosing gastrointestinal polyps has been a crucial topic in the medical field, as timely diagnosis is essential to prevent their potential malignant transformation.[4] Traditional diagnostic methods mainly include endoscopic examination and pathological histological examination. These methods are undoubtedly the gold standard for diagnosing gastrointestinal polyps, but they also have some notable limitations and invasiveness. While endoscopic examination provides direct visual observation of polyps, it may miss smaller or hidden polyps.[5] Additionally, endoscopic procedures can cause discomfort to patients and require high technical skills and experience from the physicians. Pathological histological examination, which involves microscopic analysis of biopsy tissue to determine the nature of the polyps, is highly accurate but also invasive, and sampling errors or biases may occur during the biopsy process.[6–8]
In this study, tumor markers have gradually attracted attention as a noninvasive diagnostic tool. Tumor markers are substances found in blood, body fluids, and tissues that are produced by tumor cells or by the body in response to tumors. Their level changes are often closely related to the presence and development of tumors. In recent years, with the rapid development of biotechnology, an increasing number of tumor markers have been discovered and applied in clinical practice, providing new ideas and methods for tumor diagnosis and monitoring. In the screening and diagnosis of gastrointestinal tumors, tumor markers such as carcinoembryonic antigen (CEA),[9] alpha-fetoprotein (AFP),[10] carbohydrate antigen (CA) 125,[11] CA199,[12] and prothrombin time (PT)[13] have been widely used. Changes in the serum levels of these markers often reflect the presence and progression of gastrointestinal tumors. For example, CEA is a broad-spectrum tumor marker, and its elevated levels are closely related to the occurrence and progression of various gastrointestinal tumors. CA199 is primarily used for the diagnosis and monitoring of pancreatic and bile duct cancers, while CA125 is commonly used for the diagnosis and monitoring of ovarian cancer. These markers have shown promising applications in the diagnosis of gastrointestinal tumors.
However, despite the widespread application of tumor markers in oncology, the expression levels of these markers in adenomatous gastrointestinal polyps in elderly men and their correlation with polyp characteristics require further study. Currently, there is a lack of systematic research on the value of these markers in the diagnosis of adenomatous polyps, especially in the specific population of elderly men.[14–16] Additionally, since the sensitivity and specificity of individual markers are often limited, the strategy of combining multiple markers to improve diagnostic accuracy is also worth exploring in depth.[17,18]
To investigate the expression levels of CEA, AFP, CA125, CA199, and PT in adenomatous gastrointestinal polyps in elderly men and their correlation with polyp characteristics. It evaluates their diagnostic value for polyps and explores the contribution of combined detection strategies to improving diagnostic accuracy. Through this research, we hope to provide more precise biomarkers for the early diagnosis and treatment of adenomatous gastrointestinal polyps in elderly men, ensuring better health protection for this population. This study will also provide scientific evidence for clinical screening and diagnosis, contributing positively to optimizing clinical screening strategies and improving early diagnosis rates.
2. Materials and methods
2.1. Study subjects
This study was approved by the Ethics Committee of Shangrao Municipal Hospital. This study collected data from elderly male patients who underwent endoscopic examination and were diagnosed with gastrointestinal polyps at the Gastroenterology Department of our hospital from January 2022 to June 2024. The total sample size was 90 patients, all aged 60 years or older. All patients signed informed consent forms and agreed to participate in this study.
2.2. Grouping and inclusion/exclusion criteria
The study subjects were divided into 3 groups: Adenomatous polyp group: This group included patients diagnosed with adenomatous polyps through endoscopic examination and pathological histological examination. Nonadenomatous polyp group: This group comprised patients diagnosed with nonadenomatous polyps through endoscopic examination and pathological histological examination. Healthy control group: This group consisted of healthy elderly men with no history of gastrointestinal diseases and normal endoscopic findings.
2.2.1. Inclusion criteria
Age ≥60 years and male. All included patients must undergo endoscopic examination and be diagnosed with gastrointestinal polyps (pathological examination). Pathological histological examination results must be clear and accurate to distinguish between adenomatous and nonadenomatous polyps. All included patients must sign informed consent forms and agree to participate in this study.
2.2.2. Exclusion criteria
Patients with other severe chronic diseases, such as heart, liver, or kidney failure, were excluded. Patients who recently received treatments such as radiotherapy, chemotherapy, or immunotherapy that could affect tumor marker levels were also excluded. Patients with other gastrointestinal tumors were not included in this study.
Strict grouping and inclusion/exclusion criteria were implemented to ensure the accuracy of the samples and the reliability of the study, thereby allowing for a more precise evaluation of the value of tumor markers in the diagnosis of adenomatous gastrointestinal polyps.
2.3. Detection indicators
To evaluate the relationship between adenomatous gastrointestinal polyps and a series of tumor markers. Therefore, we primarily measured the following tumor markers:
2.3.1. Carcinoembryonic antigen
CEA is a broadspectrum tumor marker, elevated in various gastrointestinal tumors, particularly with high sensitivity and specificity in colorectal cancer.[19]
2.3.2. Alpha-fetoprotein
Although AFP is mainly used for diagnosing liver and ovarian cancers, recent studies suggest that AFP levels may also change in gastrointestinal tumors, thus it was included in this study.[20]
2.3.3. Carbohydrate antigen 125
CA125 is mainly used as a marker for ovarian cancer but has also been reported to be elevated in other gastrointestinal tumors.[21]
2.3.4. Carbohydrate antigen 199
CA199 is a sensitive marker for pancreatic and bile duct cancers but is also elevated in other gastrointestinal tumors.[12]
2.3.5. Prothrombin time
Although PT is typically used to evaluate the liver’s ability to synthesize coagulation factors, recent studies have found abnormalities in PT in certain tumors.[13]
2.4. Detection methods
To ensure the accuracy of the detection results, all patients were required to fast before undergoing endoscopic examination, and 5 mL of venous blood was collected. The collected blood samples were centrifuged to separate the serum, which was then immediately stored in a freezer at 80°C for subsequent testing.
This study used a fully automated electrochemiluminescence immunoassay analyzer for detecting tumor markers. This instrument is characterized by high sensitivity, high specificity, and a high degree of automation, ensuring the accuracy and reliability of the detection results. The test kits used with the instrument were from reputable manufacturers and underwent strict quality control to ensure the accuracy of the test results.
The detection process was carried out strictly according to the instructions of the test kits and the operation procedures of the instrument. First, the serum samples to be tested were taken out of the freezer, thawed, and mixed well. Then, the samples were added to the sample slots of the fully automated electrochemiluminescence immunoassay analyzer, and the corresponding detection parameters were set according to the instrument’s operation interface. The instrument automatically performed sample preprocessing, adding reagents, incubating, washing, and detecting steps, ultimately yielding the concentration values of the tumor markers. During the detection process, we closely monitored the operational status of the instrument to ensure the smooth progress of the detection process. Additionally, each sample was tested in duplicate to ensure the accuracy and reliability of the results.
2.5. Statistical methods
Statistical efficacy analysis was conducted through G*Power software, α = 0.05, β = 0.2 (i.e., statistical efficacy is 80%), and according to the existing literature and research experience, we assumed that the effect size was 0.5 (medium effect). We calculated that a sample size of about 30 patients per group was needed to achieve sufficient statistical power to detect significant differences between groups. Data analysis was performed using SPSS 30.0 statistical software. Measurement data were expressed as mean ± standard deviation and compared between groups using independent sample t tests or Mann–Whitney U tests. Count data were expressed as percentages (%) and compared between groups using χ² tests or Fisher exact tests. Receiver operating characteristic (ROC) curves were plotted to calculate the sensitivity and specificity of each tumor marker and to determine the optimal cutoff values. Combined detection strategies were evaluated using logistic regression or random forest methods to improve diagnostic accuracy. All statistical tests were 2-sided, with P < .05 indicating statistically significant differences.
For the missing data problem in this study, we conducted a detailed examination of all key variables and found that a small number of data were missing (missing rate less than 5%). For these missing data, we use the multiple imputation method of SPSS software to reduce the bias caused by missing data. Multiple interpolation improves the robustness of the estimated results by generating multiple complete data sets and combining them with the model for analysis. After the interpolation is complete, we conduct a joint analysis of all data sets and report the combined results in the final statistical analysis. This processing method can minimize the impact of missing data on the analysis results and ensure the robustness and reliability of the results.
3. Results
3.1. Comparison of relevant indicators between groups
This study compared changes in various serum markers and routine blood indicators among the adenomatous polyp group, nonadenomatous polyp group, and healthy control group. The results showed that the levels of CEA and CA199 were significantly higher in the adenomatous polyp group than in the nonadenomatous polyp group and the healthy control group (Table 1). This finding suggests that CEA and CA199 might have potential value in diagnosing adenomatous polyps. Further analysis revealed that the levels of AFP and CA125 were also significantly higher in the adenomatous polyp group compared to the healthy control group, further enhancing the potential diagnostic value of these markers for adenomatous polyps. Additionally, the PT was significantly higher in the adenomatous polyp group compared to the nonadenomatous polyp group and the healthy control group, which may reflect some abnormal state in the coagulation system of patients with adenomatous polyps. By comparing changes in various serum markers and routine blood indicators among different groups, this study revealed biological differences between adenomatous and nonadenomatous polyps, providing valuable reference information for the diagnosis and treatment of adenomatous polyps.
Table 1.
Relevant indicators of each group [M(Q1–Q3)].
| Group | n | CEA (ng/mL) | AFP (ng/mL) | CA125 (U/mL) | CA199 (U/mL) |
|---|---|---|---|---|---|
| Adenomatous polyp group | 30 | 2.67 (1.99–3.42) | 2.36 (1.76–3.56) | 9.08 (6.07–11.93) | 11.68 (7.37–19.27) |
| Nonadenomatous polyp group | 30 | 1.60 (1.26–2.21) | 2.18 (1.89–2.92) | 8.65 (5.88–10.96) | 7.87 (3.23–17.18) |
| Healthy group | 30 | 1.72 (0.97–2.36) | 2.17 (1.52–3.09) | 5.60 (4.73–7.58) | 9.96 (4.29–16.78) |
| Group | n | WBC (×10⁹/L) | NEU (×10⁹/L) | HGB (g/L) | PLT (×10⁹/L) |
| Adenomatous polyp group | 30 | 5.70 (4.70–6.70) | 3.50 (2.80–4.00) | 141.00 (125.00–151.00) | 170.00 (148.00–189.00) |
| Nonadenomatous polyp group | 30 | 5.75 (4.98–6.70) | 3.40 (2.80–4.29) | 139.50 (130.75–145.25) | 165.50 (150.00–194.50) |
| Healthy group | 30 | 5.70 (4.50–6.95) | 3.30 (2.34–4.28) | 138.00 (129.50–146.00) | 175.00 (147.50–196.00) |
| Group | n | PT (U/mL) | APTT (U/mL) | FIB (g/L) | hs-CRP (g/L) |
| Adenomatous polyp group | 30 | 13.00 (12.70–14.00) | 35.10 (33.00–38.10) | 3.14 (2.81–3.67) | 1.00 (0.50–1.90) |
| Nonadenomatous polyp group | 30 | 12.80 (12.60–13.34) | 36.15 (34.55–38.03) | 3.17 (2.84–3.56) | 1.95 (0.75–3.20) |
| Healthy group | 30 | 12.90 (12.50–13.40) | 35.00 (32.10–37.75) | 3.05 (2.54–3.82) | 1.40 (0.55–3.80) |
AFP = alpha-fetoprotein, CA125 = carbohydrate antigen 125, CA199 = carbohydrate antigen 199, CEA = carcinoembryonic antigen, PT = prothrombin time.
3.2. Diagnostic value of various indicators for adenomatous polyps
Through ROC curve analysis, we assessed the effectiveness of different indicators in diagnosing adenomatous polyps (Fig. 1 and Table 2). The results showed that among the individual tests, CA125 had the highest diagnostic performance, indicating that CA125 has high sensitivity and specificity in diagnosing adenomatous polyps. Furthermore, we explored the effectiveness of combined diagnostics. By comparing different combinations of markers, we found that the combination of CEA and CA125 had the highest diagnostic performance among the 2-marker combinations. For the 3-marker combinations, the combination of CEA, CA125, and AFP showed the best diagnostic effect. In the 4-marker combinations, the combination of CEA, CA125, AFP, and PT had the highest diagnostic performance. Finally, in the 5-marker combination, although more indicators were included, the diagnostic performance did not further improve, which may be because some markers contributed less to the diagnosis of adenomatous polyps. Notably, CEA and CA125 were included in all combined diagnostic combinations, emphasizing the importance of these 2 markers in the diagnosis of adenomatous polyps.
Figure 1.
The ROC curves of different combined diagnostic combinations, visually demonstrating their diagnostic performance. ROC = receiver operating characteristic curve.
Table 2.
Specific diagnostic performance data of individual indicators and combined diagnostic combinations, including sensitivity, specificity, and AUC values.
| Indicator | AUC | 95% CI | Sensitivity, % | Specificity, % | P |
|---|---|---|---|---|---|
| CEA | 0.731 | 0.659–0.803 | 0.703 | 0.704 | <0.01 |
| AFP | 0.598 | 0.517–0.680 | 0.757 | 0.444 | 0.02 |
| CA125 | 0.734 | 0.662–0.807 | 0.631 | 0.778 | <0.01 |
| CA199 | 0.583 | 0.501–0.665 | 0.766 | 0.42 | 0.049 |
| PT | 0.586 | 0.505–0.666 | 0.324 | 0.852 | 0.043 |
| CEA + AFP | 0.745 | 0.672–0.817 | 0.586 | 0.815 | <0.01 |
| CEA + CA125 | 0.768 | 0.700–0.835 | 0.676 | 0.802 | <0.01 |
| CEA + CA199 | 0.73 | 0.685–0.801 | 0.541 | 0.84 | <0.01 |
| CEA + PT | 0.762 | 0.694–0.831 | 0.694 | 0.765 | <0.01 |
| AFP + CA125 | 0.74 | 0.667–0.813 | 0.793 | 0.63 | <0.01 |
| AFP + CA199 | 0.625 | 0.546–0.703 | 0.396 | 0.815 | <0.01 |
| AFP + PT | 0.658 | 0.581–0.735 | 0.622 | 0.642 | <0.01 |
| CA125 + CA199 | 0.745 | 0.674–0.816 | 0.766 | 0.667 | <0.01 |
| CA125 + PT | 0.744 | 0.672–0.815 | 0.73 | 0.716 | <0.01 |
| CA199 + PT | 0.604 | 0.525–0.683 | 0.27 | 0.938 | 0.014 |
| CEA + AFP + CA125 | 0.777 | 0.711–0.844 | 0.784 | 0.679 | <0.01 |
| CEA + AFP + CA199 | 0.745 | 0.673–0.816 | 0.658 | 0.741 | <0.01 |
| CEA + AFP + PT | 0.769 | 0.701–0.837 | 0.658 | 0.802 | <0.01 |
| CEA + CA125 + CA199 | 0.766 | 0.699–0.834 | 0.82 | 0.469 | <0.01 |
| CEA + CA125 + PT | 0.775 | 0.709–0.842 | 0.667 | 0.815 | <0.01 |
| CEA + CA199 + PT | 0.757 | 0.688–0.826 | 0.631 | 0.815 | <0.01 |
| AFP + CA125 + CA199 | 0.754 | 0.683–0.826 | 0.937 | 0.531 | <0.01 |
| AFP + CA125 + PT | 0.745 | 0.672–0.817 | 0.874 | 0.593 | <0.01 |
| AFP + CA199 + PT | 0.663 | 0.578–0.738 | 0.468 | 0.815 | <0.01 |
| CA125 + CA199 + PT | 0.75 | 0.679–0.820 | 0.811 | 0.617 | <0.01 |
| CEA + AFP + CA125 + CA199 | 0.78 | 0.714–0.845 | 0.82 | 0.63 | <0.01 |
| CEA + AFP + CA125 + PT | 0.785 | 0.719–0.850 | 0.784 | 0.679 | <0.01 |
| CEA + AFP + CA199 + PT | 0.768 | 0.701–0.836 | 0.649 | 0.79 | <0.01 |
| CEA + CA125 + CA199 + PT | 0.775 | 0.708–0.841 | 0.613 | 0.852 | <0.01 |
| AFP + CA125 + CA199 + PT | 0.756 | 0.686–0.827 | 0.937 | 0.494 | <0.01 |
| CEA + AFP + CA125 + CA199 + PT | 0.787 | 0.722–0.852 | 0.766 | 0.691 | <0.01 |
AFP = alpha-fetoprotein, CA125 = carbohydrate antigen 125, CA199 = carbohydrate antigen 199, CEA = carcinoembryonic antigen, PT = prothrombin time.
3.3. Impact of adenomatous polyp size and number on CEA, CA125, CA199, and PT levels
Our study also explored the impact of the size and number of adenomatous polyps on the levels of CEA, CA125, CA199, and PT (Table 3). The results indicated that polyp size positively affected all 4 indicators, meaning that the larger the polyps, the higher the levels of these markers (P < .05). This finding suggests that polyp size may be an important consideration in the evaluation of adenomatous polyps. Additionally, we found that the number of polyps positively affected the levels of CEA, CA125, and PT (P < .05), but had no significant impact on CA199. This implies that the number of polyps may also be an important factor to consider, especially when evaluating CEA, CA125, and PT levels.
Table 3.
Specific relationship between the size and number of adenomatous polyps and various index levels.
| Constant | Unit | Size B value | Size t value | Size P value | Quantity B value | Quantity t value | Quantity P value |
|---|---|---|---|---|---|---|---|
| CEA | ng/mL | 3.21 | 4.32 | <0.001 | 0.15 | 2.98 | 0.003 |
| AFP | ng/mL | 2.59 | 3.17 | 0.002 | −1.21 | −1.18 | 0.24 |
| CA125 | U/mL | 9.45 | 1.15 | 0.011 | 0.72 | 4.56 | <0.001 |
| CA199 | U/mL | 5.28 | 2.09 | 0.041 | 0.37 | 0.92 | 0.36 |
| PT | U/mL | 5.78 | 2.62 | 0.01 | 0.26 | 3.21 | 0.002 |
AFP = alpha-fetoprotein, CA125 = carbohydrate antigen 125, CA199 = carbohydrate antigen 199, CEA = carcinoembryonic antigen, PT = prothrombin time.
4. Discussion
Adenomatous polyps are a common benign lesion in the digestive system, and their clinical diagnosis and treatment have been a focus of medical research. In recent years, with advancements in serological marker detection technology, increasing attention has been paid to their diagnostic value in adenomatous polyps. This study aimed to explore the potential value of these markers in diagnosing adenomatous polyps by comparing various serum markers and routine blood indicators among the adenomatous polyp group, nonadenomatous polyp group, and healthy control group, providing new insights for clinical diagnosis.
4.1. Application of serum markers in diagnosing adenomatous polyps
Serum markers play a crucial role in diagnosing adenomatous polyps, and their detection results often provide valuable diagnostic information for physicians.[22,23] The results of this study showed that the levels of CEA and CA199 were significantly elevated in the adenomatous polyp group compared to the nonadenomatous polyp group and healthy control group. This finding offers new perspectives for understanding the biological characteristics of adenomatous polyps and their diagnostic methods.
CEA is a glycoprotein expressed in various tumor cells, widely present on the surface of cancer cells differentiated from endodermal cells, acting as a structural protein of the cell membrane.[24] As a broadspectrum tumor marker, CEA has important applications in the diagnosis and monitoring of various malignant tumors, including gastrointestinal tumors, lung cancer, and breast cancer. The significant elevation of CEA levels in the adenomatous polyp group may indicate a certain biological link between adenomatous polyps and malignant tumors or suggest that adenomatous polyps have potential malignant transformation risks. Therefore, detecting CEA levels is of significant reference value for diagnosing and assessing the risk of adenomatous polyps.
Similar to CEA, CA199 is also a marker expressed in various tumors, particularly having high sensitivity in pancreatic cancer.[25] The elevation of CA199 levels is often closely related to the malignancy, metastasis, and prognosis of tumors. In this study, the significant increase of CA199 in the adenomatous polyp group also suggests a possible connection between adenomatous polyps and digestive system tumors like pancreatic cancer. Although adenomatous polyps are benign, their altered biological characteristics might indicate a risk of transformation to malignant tumors. Thus, monitoring changes in CA199 levels can help better assess the malignancy risk of adenomatous polyps, providing more accurate basis for clinical diagnosis and treatment.
In addition to CEA and CA199, this study also found that AFP and CA125 levels were elevated in the adenomatous polyp group.[26,27] AFP is a protein produced by fetal liver, yolk sac, and gastrointestinal cells, with important applications in diagnosing liver cancer and ovarian cancer. CA125 is closely related to ovarian cancer, and its elevation is often associated with the malignancy, metastasis, and prognosis of ovarian cancer. The elevated levels of AFP and CA125 in the adenomatous polyp group may indicate a biological link between adenomatous polyps and these malignant tumors,[28,29] or suggest that adenomatous polyps have specific biological characteristics. These findings provide new clues for further exploring the biological characteristics of adenomatous polyps.
Finally, this study found that the PT level in the adenomatous polyp group was significantly higher than in the nonadenomatous polyp group and healthy control group. PT is an indicator reflecting the function of the coagulation system, and its elevation may indicate abnormalities in the coagulation system of patients. This finding suggests that, in diagnosing adenomatous polyps, attention should not only be paid to traditional tumor markers but also to changes in the coagulation system. Abnormalities in the coagulation system may be closely related to the biological characteristics and malignancy risk of adenomatous polyps. Thus, monitoring changes in PT levels can better assess the condition and prognosis of adenomatous polyps. In summary, serum markers have important applications in diagnosing adenomatous polyps. By detecting changes in markers such as CEA, CA199, AFP, CA125, and PT, we can better understand the biological characteristics of adenomatous polyps, assess their malignancy risk, and guide clinical diagnosis and treatment. These findings provide new insights for further exploring the pathogenesis, prevention, and treatment of adenomatous polyps.
4.2. Advantages of combined diagnosis in the diagnosis of adenomatous polyps
In the field of adenomatous polyp diagnosis, traditional single marker detection methods, although clinically valuable, may have limitations in certain cases.[30] Therefore, in recent years, combined diagnostic strategies have gradually gained attention from clinicians. This study used ROC curve analysis to comprehensively evaluate the efficacy of different markers in diagnosing adenomatous polyps and discussed the advantages of combined diagnosis.
First, we observed that in single-marker detection, CA125 showed relatively high diagnostic efficacy. CA125, as a carbohydrate antigen, has its unique place among various tumor markers, particularly showing high sensitivity in the diagnosis of ovarian cancer. However, in this study, we found that CA125 also has value in diagnosing adenomatous polyps. This may be related to certain biological characteristics of adenomatous polyps, such as their similarity in cell origin or differentiation pathways with organs like the ovaries. However, the limitation of single-marker detection lies in the difficulty of achieving optimal sensitivity and specificity simultaneously. Therefore, we further explored the application of combined diagnosis in the diagnosis of adenomatous polyps. By combining multiple markers, we found that combined diagnosis can significantly improve the sensitivity and specificity of diagnosis. Specifically, in a 2-marker combined diagnosis, the combination of CEA and CA125 showed the highest diagnostic efficacy. CEA, as a broad-spectrum tumor marker expressed in various malignant tumors, complements CA125 and enhances the accuracy of diagnosis. Furthermore, in a 3-marker combined diagnosis, the combination of CEA, CA125, and AFP showed the best diagnostic performance. AFP, as an alpha-fetoprotein, is also expressed in tumors such as liver cancer and ovarian cancer, providing additional information support for combined diagnosis. In a 4-marker combined diagnosis, the combination of CEA, CA125, AFP, and PT showed the highest diagnostic efficacy. PT, as an indicator reflecting the function of the coagulation system, its abnormalities may be related to certain biological characteristics of adenomatous polyps, thereby further enhancing the accuracy of combined diagnosis.
4.3. The impact of adenomatous polyp size and number on marker levels
In addition to serum markers and combined diagnosis, the size and number of adenomatous polyps are also important factors affecting their diagnosis and assessment.[22,31,32] This study found that the size and number of adenomatous polyps have a certain impact on the levels of CEA, CA125, CA199, and PT. Specifically, as the size of adenomatous polyps increases, the levels of these markers tend to increase correspondingly. This may be related to the biological characteristics of adenomatous polyps, such as enhanced cell proliferation and metabolism. In addition, an increase in the number of polyps also affects the levels of CEA, CA125, and PT.[28] This impact may be related to the influence of polyps on the body’s metabolism and coagulation system, leading to abnormal levels of these markers. This finding suggests that in the assessment of adenomatous polyps, in addition to monitoring changes in serum markers and routine blood indicators, clinical factors such as the size and number of polyps should also be considered. These factors may have an impact on the biological characteristics and diagnosis and treatment of adenomatous polyps.[33] Therefore, in clinical practice, doctors should comprehensively consider these factors to formulate more comprehensive and accurate diagnosis and treatment plans.
4.4. Study limitations and future prospects
Although this study has made some meaningful findings in the diagnosis of adenomatous polyps, there are still some limitations. First, the sample size of this study is relatively small, which may affect the stability and reliability of the results. Future studies can expand the sample size to further validate the conclusions of this study. Second, this study mainly focused on changes in serum markers and routine blood indicators, without involving other potential biological markers or molecular markers. Future research can further explore the application value of these markers in the diagnosis of adenomatous polyps. In addition, although we minimized the impact of serious chronic diseases and therapeutic interventions on tumor marker levels through strict inclusion and exclusion criteria, there may still be other confounding factors (such as other health conditions or medication use) that are not fully controlled and that may have a potential impact on marker levels. Future studies could better control for these confounders through more comprehensive adjustment models, or by using methods such as propensity score matching. Additionally, this study mainly relied on cross-sectional data analysis and did not conduct in-depth research on the development process and outcomes of adenomatous polyps. Future research can conduct longitudinal studies to further explore the biological characteristics and diagnosis and treatment methods of adenomatous polyps.
In conclusion, this study revealed the potential value of these markers in diagnosing adenomatous polyps by comparing and analyzing changes in various serum markers and routine blood indicators among the adenomatous polyp group, nonadenomatous polyp group, and healthy control group. Combined diagnosis has significant advantages in the diagnosis of adenomatous polyps, with CEA and CA125 playing important roles in combined diagnosis. Future research can further explore the application value of other biological markers in the diagnosis of adenomatous polyps, as well as the biological characteristics and diagnosis and treatment methods of adenomatous polyps.
Acknowledgments
We would like to thank the participants of this study for sharing their experiences.
Author contributions
Conceptualization: Jun Zhou, Qizhi Li.
Data curation: Jun Zhou, Qizhi Li.
Formal analysis: Jun Zhou, Qizhi Li.
Investigation: Jun Zhou.
Methodology: Jun Zhou.
Writing—original draft: Jun Zhou, Qizhi Li, Cheng Rao.
Writing—review & editing: Jun Zhou, Cheng Rao.
Abbreviations:
- AFP
- alpha-fetoprotein
- CA
- carbohydrate antigen
- CEA
- carcinoembryonic antigen
- PT
- prothrombin time.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Zhou J, Li Q, Rao C. Exploring the value and optimizing strategies of CA125, CA199, CEA, AFP, and PT in predicting adenomatous gastrointestinal polyps in elderly male patients. Medicine 2024;103:49(e40366).
Contributor Information
Qizhi Li, Email: 15779422751@163.com.
Cheng Rao, Email: 15180313977@163.com.
References
- [1].World Health Organization. Men, ageing and health: achieving health across the life span. World Health Organization; 2001. [Google Scholar]
- [2].Goldman DP, Cutler D, Rowe JW, et al. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Aff (Millwood). 2013;32:1698–705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [3].Douma KFL, Bleiker EMA, Vasen HFA, Gundy CM, Gerritsma MA, Aaronson NK. Psychological distress and quality of life of partners of individuals with familial adenomatous polyposis. Psychooncology. 2011;20:146–54. [DOI] [PubMed] [Google Scholar]
- [4].Mitsala A, Tsalikidis C, Pitiakoudis M, Simopoulos C, Tsaroucha AK. Artificial intelligence in colorectal cancer screening, diagnosis and treatment. A new era. Curr Oncol. 2021;28:1581–607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Wang Y, Tavanapong W, Wong J, Oh JH, de Groen PC. Polyp-alert: near real-time feedback during colonoscopy. Comput Methods Programs Biomed. 2015;120:164–79. [DOI] [PubMed] [Google Scholar]
- [6].Mason SE, Poynter L, Takats Z, Darzi A, Kinross JM. Optical technologies for endoscopic real-time histologic assessment of colorectal polyps: a meta-analysis. Am J Gastroenterol. 2019;114:1219–30. [DOI] [PubMed] [Google Scholar]
- [7].Babawale M, Gunavardhan A, Walker J, et al. Verification and validation of digital pathology (whole slide imaging) for primary histopathological diagnosis: all Wales experience. J Pathol Inform. 2021;12:4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Hassan C, Zullo A, Risio M, Rossini FP, Morini S. Histologic risk factors and clinical outcome in colorectal malignant polyp: a pooled-data analysis. Dis Colon Rectum. 2005;48:1588–96. [DOI] [PubMed] [Google Scholar]
- [9].Li H, Liao H, Jing B, Wang Y. Effects of coagulation function indicators and tumor markers on diagnosis and clinicopathological characteristics of endometrial cancer. Int J Biol Markers. 2023;38:214–22. [DOI] [PubMed] [Google Scholar]
- [10].Faria SC, Sagebiel T, Patnana M, et al. Tumor markers: myths and facts unfolded. Abdom Radiol. 2019;44:1575–600. [DOI] [PubMed] [Google Scholar]
- [11].Ge W, Zheng L, Chen G. The combination of seven preoperative markers for predicting patients with gastric cancer to be either stage IV or non-stage IV. Gastroenterol Res Pract. 2018;2018:1–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Mustafa MZ. Tumor diagnostic markers in primary liver cancers. Pak J Multidiscip Res. 2021;2:243–58. [Google Scholar]
- [13].Sadighbayan D, Sadighbayan K, Tohid-Kia MR, Khosroushahi AY, Hasanzadeh M. Development of electrochemical biosensors for tumor marker determination towards cancer diagnosis: recent progress. TRAC Trends Anal Chem. 2019;118:73–88. [Google Scholar]
- [14].Brosens LAA, van Hattem WA, Jansen M, et al. Gastrointestinal polyposis syndromes. Curr Mol Med. 2007;7:29–46. [DOI] [PubMed] [Google Scholar]
- [15].O’Brien MJ, Winawer SJ, Zauber AG, et al. The national polyp study: patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastroenterology. 1990;98:371–9. [PubMed] [Google Scholar]
- [16].Genta RM, Schuler CM, Robiou CI, Lash RH. No association between gastric fundic gland polyps and gastrointestinal neoplasia in a study of over 100,000 patients. Clin Gastroenterol Hepatol. 2009;7:849–54. [DOI] [PubMed] [Google Scholar]
- [17].Linnet K, Bossuyt PMM, Moons KGM, Reitsma JB. Quantifying the accuracy of a diagnostic test or marker. Clin Chem. 2012;58:1292–301. [DOI] [PubMed] [Google Scholar]
- [18].Shogilev DJ, Duus N, Odom SR, Shapiro NI. Diagnosing appendicitis: evidence-based review of the diagnostic approach in 2014. West J Emerg Med. 2014;15:859–71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Wang H, Jin W, Wan C, Zhu C. Diagnostic value of combined detection of CA72-4, CA19-9, and carcinoembryonic antigen comparing to CA72-4 alone in gastric cancer: a systematic review and meta-analysis. Transl Cancer Res. 2022;11:848–56. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Naz Z, Usman S, Saleem K, et al. Alpha-fetoprotein: a fabulous biomarker in hepatocellular, gastric and rectal cancer diagnosis. Biomed Res. 2018;29:2478–83. [Google Scholar]
- [21].Zhang M, Cheng S, Jin Y, et al. Roles of CA125 in diagnosis, prediction, and oncogenesis of ovarian cancer. Biochim Biophys Acta Rev Cancer. 2021;1875:188503. [DOI] [PubMed] [Google Scholar]
- [22].Shah R, Jones E, Vidart V, Kuppen PJK, Conti JA, Francis NK. Biomarkers for early detection of colorectal cancer and polyps: systematic review. Cancer Epidemiol Biomarkers Prev. 2014;23:1712–28. [DOI] [PubMed] [Google Scholar]
- [23].Tsang AHF, Cheng KH, Wong ASP, et al. Current and future molecular diagnostics in colorectal cancer and colorectal adenoma. World J Gastroenterol. 2014;20:3847. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [24].Sinha SR, Prakash P, Singh RK, Sinha DK. Assessment of tumor markers CA 19-9, CEA, CA 125, and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer. World J Gastrointest Surg. 2022;14:1272–84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Bharathan A, Sitaram V. Tumor markers in GI and HPB cancers. GI Surg Annu. 2019;25:139–54. [Google Scholar]
- [26].Sarandakou A, Protonotariou E, Rizos D. Tumor markers in biological fluids associated with pregnancy. Crit Rev Clin Lab Sci. 2007;44:151–78. [DOI] [PubMed] [Google Scholar]
- [27].Molina R, Bosch X, Auge JM, et al. Utility of serum tumor markers as an aid in the differential diagnosis of patients with clinical suspicion of cancer and in patients with cancer of unknown primary site. Tumor Biol. 2012;33:463–74. [DOI] [PubMed] [Google Scholar]
- [28].Gao Y, Wang J, Zhou Y, Sheng S, Qian SY, Huo X. Evaluation of serum CEA, CA19-9, CA72-4, CA125 and ferritin as diagnostic markers and factors of clinical parameters for colorectal cancer. Sci Rep. 2018;8:2732. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [29].Lee SH, Koh YW, Roh HJ, Cha HJ, Kwon Y-S. Ovarian microcystic stromal tumor: a novel extracolonic tumor in familial adenomatous polyposis. Genes Chromosomes Cancer. 2015;54:353–60. [DOI] [PubMed] [Google Scholar]
- [30].Vatandoost N, Ghanbari J, Mojaver M, et al. Early detection of colorectal cancer: from conventional methods to novel biomarkers. J Cancer Res Clin Oncol. 2016;142:341–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [31].Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. Ann Intern Med. 1993;119:836–43. [DOI] [PubMed] [Google Scholar]
- [32].Imperiale TF, Gruber RN, Stump TE, Emmett TW, Monahan PO. Performance characteristics of fecal immunochemical tests for colorectal cancer and advanced adenomatous polyps: a systematic review and meta-analysis. Ann Intern Med. 2019;170:319–29. [DOI] [PubMed] [Google Scholar]
- [33].Sawicki T, Ruszkowska M, Danielewicz A, Niedźwiedzka E, Arłukowicz T, Przybyłowicz KE. A review of colorectal cancer in terms of epidemiology, risk factors, development, symptoms and diagnosis. Cancers. 2021;13:2025. [DOI] [PMC free article] [PubMed] [Google Scholar]

