miRNA-143 as a potential biomarker in the detection of bladder cancer: a meta-analysis

Abstract

Aim: This study aimed to systematically evaluate the value of miRNA-143 in the early detection of bladder cancer (BCa). Methods: CNKI, WanFang, PubMed and Wiley Online Library databases were explored according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. A random-effects model was used to obtain pooled sensitivity, specificity and other related indicates. Results: Six studies were included for analysis. The overall pooled sensitivity and specificity were 0.80 (95% CI: 0.74–0.85) and 0.85 (95% CI: 0.78–0.91), and the area under the curve was 0.88 (95% CI: 0.85–0.91). Coupled with miR-100, it showed better diagnostic power (area under the curve: 0.95). Conclusion: miRNA-143 may serve as a promising noninvasive tool for the early detection of BCa.

Plain language summary

Bladder cancer (BCa) is a common and deadly malignant tumor worldwide; however, noninvasive diagnosis can significantly improve the prognosis of patients. Recently, miRNAs have emerged as potential diagnostic biomarkers for BCa. Among them, miRNA-143 has shown promising results in several studies. This meta-analysis aimed to evaluate the overall diagnostic accuracy of miRNA-143 for BCa through a systematic review and meta-analysis of six published articles. Excitingly, the results of this meta-analysis suggest that miRNA-143 has potential diagnostic value in BCa. Particularly, miRNA-143 combined with miRNA-100 maintained better competence. Besides, miRNA-143 in plasma exhibited better diagnostic strength than that in urine. The authors believe that their study provides valuable insights into the use of miRNA-143 as a diagnostic biomarker for BCa.

Plain language summary

Summary points.

• This study confirmed the promising diagnostic performance of miRNA-143 using meta-analysis.

• miRNA-143 had more potential for diagnosing bladder cancer (BCa) within Asian populations.

• The heterogeneity based on ethnicities might be the result of the single nucleotide polymorphisms of the PAI-1 gene.

• miRNA-143 in plasma performed better compared with that in urine.

• Specific proteins in plasma might help isolate the miRNA-143 and improve its diagnostic performance.

• miRNA-143 coupled with miRNA-100 showed the best diagnostic performance among various combinations.

• More studies only focus between healthy population and non-muscle-invasive BCa or muscle-invasive BCa patients and healthy are demanding.

• Ununified screening protocols for miRNA-143 hinder the verification of its actual diagnostic value.

Bladder cancer (BCa) is the ninth most common malignancy worldwide, with a mortality rate ranking 13th globally. In 2020, the GLOBOCAN 2020 database reported approximately 573,000 new cases (3% of all cancer sites) and 212,000 new deaths (2.1% of all cancer sites) related to BCa. The incidence of BCa is notably higher in men (9.5/100,000) and the death rate stands at 3.3/100,000 [1]. Uroepithelial cell carcinoma accounts for 90–95% of all bladder cancer cases, with over 70% classified as non-muscle-invasive BCa. Furthermore, there is a relatively high recurrence rate (30–80%) within 5 years post-tumor excision [2]. Presently, cystoscopy and urine cytology serve as the gold standards for BCa diagnosis. Cystoscopy exhibits excellent specificity (SPE) in detecting BCa; however, its low sensitivity (SEN) hinders its practical utility. Moreover, cystoscopy is both costly and invasive, potentially leading to reduced patient compliance. On the other hand, urine cytology offers a noninvasive method for BCa diagnosis with an SPE of 94%, but its SEN for detecting early-stage or low-grade malignancies falls below 40% [3]. Hence, there is a pressing need for novel noninvasive technologies to enhance diagnostic accuracy.

miRNAs are single-stranded RNA molecules, encoded by endogenous genes, typically 22 nucleotides in length, and play a crucial role in gene expression regulation through mechanisms such as target degradation and translational silencing [4]. Dysregulation of miRNAs has been extensively documented across various solid tumors [5]. Moreover, miRNAs have demonstrated stability in bodily fluids such as urine and plasma [6]. Consequently, miRNAs hold significant promise as noninvasive, specific and stable biomarkers for cancer screening [7].

miRNA-143, classified as an oncomiRNA, exhibits aberrant expression patterns across various cancers, including pancreatic neoplasm [8], lung carcinoma [9], hepatocytes [10] and gastric cancer [11]. Numerous studies have observed downregulation of miRNA-143 in the serum of BCa patients compared with non-BCa controls, suggesting its potential as a diagnostic tool for BCa [^12-14]. However, to date, no meta-analysis has specifically assessed the diagnostic efficacy of miRNA-143 in BCa detection. Therefore, the objective of this meta-analysis is to evaluate the existing literature on miRNA-143 in body fluids for BCa diagnosis and assess its diagnostic accuracy.

Materials & methods

Bibliographic retrieval

This systematic study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol [15]. Bibliographic retrieval was performed up to March 2023, utilizing international databases (PubMed and Wiley Online Library) and Chinese databases (CNKI and WanFang). The meta-analysis utilized search criteria encompassing terms such as (bladder cancer OR bladder tumor OR bladder carcinoma OR bladder neoplasm) AND (miRNA-143 OR miR-143 OR microRNA-143) AND (diagnosis OR early detection OR diagnostic accuracy). The search encompassed records from inception until 31 March 2023, with predominantly English or Chinese language articles included. Additionally, the reference lists of original studies were manually screened to identify further eligible studies, a critical component of the study methodology.

Study selection criteria

Inclusion criteria

BCa patients must be confirmed by histopathology; the studies must specifically investigate the relationship between BCa and miRNA-143; control group subjects must have a clear cancer history and articles must provide sufficient data to construct a 2 × 2 diagnostic contingency table.

Exclusion criteria

Excluded were abstracts, case reports and comments; studies with insufficient data for meta-analysis or involving fewer than 30 subjects and animal and cell research.

Data extraction

Two investigators, J Li and H Li, were tasked with data extraction in accordance with the PRISMA protocol. Data extraction encompassed the following elements: country, bibliometric details (including author names and publication year), title, characteristics of both control and case groups (such as median or average age, gender distribution and sample size), information pertaining to diagnostic performance (including SPE, SEN or other relevant metrics), cutoff value(s) and array type.

Quality evaluation of selected literature

The eligible literature was assessed using the QUADAS-2 tool by two independent reviewers across four key domains. For the risk of bias assessment, the reviewers evaluated all four domains using ‘yes’, ‘no’ or ‘unclear’ responses, while three domains were assessed similarly for applicability concerns. The results from QUADAS-2 informed the evaluation of the overall quality of the included literature and primarily identified potential sources of heterogeneity. Consensus on all discrepancies was reached through discussion [16].

Statistical analysis

The diagnostic meta-analysis of miRNA-143 was conducted using Meta-DiSc 1.4 and Stata 14.0 analytical software [17]. Heterogeneity among selected studies was investigated using p-values and Higgins' I² value. A fixed-effects model was applied in cases of low heterogeneity (I² <50%), while a random-effects model was recommended otherwise. Pooled SEN with a 95% CI and combined SPE were the main indices used to analyze the diagnostic value of miRNA-143. The positive likelihood ratio represented the variation in the probability of a positive diagnosis in patients who receive a positive test, while the negative likelihood ratio demonstrated the change in the likelihood of a negative diagnosis in patients who display a negative test. Additionally, the diagnostic odds ratio (DOR) was calculated to measure the effectiveness of the diagnostic test. These three indices were employed to evaluate clinical diagnostic ability. Symmetrical summary receiver operating characteristic curves were preferred, and the area under the curve (AUC) from the summary receiver operating characteristic curve was another index used to assess potential diagnostic utility. The Spearman correlation coefficient was utilized to investigate the presence of the threshold effect. Subgroup analysis and meta-regression analysis were employed to identify sources of variation among selected studies. Sensitivity analysis was performed using a specific Stata command ‘midas tp fp fn tn, modchk(all)’ to build relevant plots. Fagan's nomogram, a graphical tool, was used to assess the clinical utility of miRNA-143 in diagnosing BCa. Deeks' funnel plot was another useful method used to evaluate publication bias.

Results

Qualified studies

As depicted in Figure 1, a total of 1618 records were initially identified. After eliminating 450 duplicate records, 1168 studies advanced to the next stage. Subsequent screening, which included title, abstract and keyword assessments, led to the exclusion of 1138 articles, leaving 30 articles for full-text assessment. Among these, ten papers focused on the prognostic significance of miRNA-143, five were centered on cell or animal investigations, six lacked sufficient data and three had inadequate sample sizes. Ultimately, six eligible studies were included in this meta-analysis.

Figure 1.

Preferred reporting items for systematic reviews and meta-analyses flow diagram of the screening procedure for the search of qualified studies in the meta-analysis.

BC: Bladder cancer.

Study characteristics

The analysis comprised six literature pieces [^18-23] assessing the efficacy of miRNA-143 in early BCa detection, involving a total of 395 BCa patients and 390 controls. One study's control group [20] included healthy individuals and non-BCa controls (urinary tract infection, urolithiasis and prostatic hyperplasia), while the others solely included healthy controls. Five articles were conducted in China between 2017 and 2021, with one study completed in Africa in 2016. All selected studies employed quantitative reverse-transcription PCR for identification. Moreover, four studies utilized plasma specimens, while the remaining two employed urine (Supplementary Table 1). Notably, all selected studies examined the diagnostic value of various miRNA panels, consisting of seven different combinations (Supplementary Table 2).

Quality assessment

Figure 2 illustrates that all included articles underwent evaluation using the QUADAS-2 system, which is noteworthy. Concerning the risk of bias, one study demonstrated a low risk across three domains, while three other publications exhibited a very low risk in two domains, and only one study had a low risk in one domain. Regarding applicability concerns, the articles met the criteria, with a low likelihood in all three domains, with percentages exceeding 70% or even reaching 100% for the index test, indicating minimal applicability concerns. There were no instances of high risk or concerns in any domain. However, in the flow and timing domain, unclear responses were prevalent. Nearly all authors did not specify whether all patients or controls were categorized using the same standard of reference, or if patients were lost during the study, resulting in incomplete data collection. Nonetheless, overall, the selected articles demonstrated promising quality.

Figure 2.

Summary of the QUADAS-2 assessment of six qualified articles.

Diagnostic accuracy of miR-143 in BCa

Due to substantial interstudy heterogeneity in SEN data (I² = 56.80%) and SPE data (I² = 72.03%), the random-effects model was chosen. The forest plot in Figure 3A illustrates that the pooled SEN was 0.80 (95% CI: 0.74–0.85) for distinguishing BCa patients from healthy controls, and the combined SPE was 0.85 (95% CI: 0.78–0.91). Additionally, the AUC was 0.88 (95% CI: 0.85–0.91), indicating good diagnostic accuracy for miRNA-143. Based on the combined parameters, the positive likelihood ratio was calculated as 5.4 (95% CI: 3.6–8.0), and the negative likelihood ratio was 0.24 (95% CI: 0.19–0.30). Furthermore, the DOR was 23 (95% CI: 15–35).

Figure 3.

Diagnostic accuracy of miRNA-143 for bladder cancer.

(A) Combined sensitivity and specificity between BCa patients and a normal control population. (B) Summary receiver operation characteristic curve between BCa patients and a normal control population.

AUC: Area under the curve; BCa: Bladder cancer; df: Degrees of freedom; SENS: Sensitivity; SPEC: Specificity; SROC: Summary receiver operating characteristic curve.

To assess the threshold effect, the summary receiver operating characteristic curve was plotted (Figure 3B). The Spearman correlation coefficient of 0.116 (p = 0.827) suggested that there was no threshold effect.

Subgroup analysis

The authors performed a subgroup analysis based on the specimen type (plasma or urine), sample size (less than or equal to 100 or more than 100) and miRNA profile (miRNA-143 alone, miRNA-143 combined with another miRNA or miRNA-143 combined with two other miRNA assays). The diagnostic indices for each subgroup are presented in Table 1.

Table 1.

Subgroup analysis of included studies based on specimen, sample size and miRNA profile between bladder cancer patients and non-bladder cancer patients.

Subgroup analysis	n	Sensitivity (95% CI)	Specificity (95% CI)	Positive likelihood ratio (95% CI)	Negative likelihood ratio (95% CI)	Diagnostic odds ratio (95% CI)	Area under the curve
Specimen
Urine	2	0.84 (0.61–0.89)	0.82 (0.73–0.88)	4.6 (2.8–7.6)	0.20 (0.07–0.55)	24 (6–92)	0.84
Plasma	4	0.79 (0.74–0.83)	0.87 (0.82–0.91)	6.2 (3.0–12.7)	0.26 (0.21–0.32)	25 (16–41)	0.89
Sample size
≤100	2	0.49 (0.39–0.58)	0.55 (0.24–0.83)	1.1 (0.5–2.2)	0.94 (0.52–1.68)	1 (0–4)	0.49
>100	4	0.78 (0.74–0.83)	0.85 (0.80–0.88)	5.1 (2.8–9.2)	0.27 (0.21–0.34)	21 (11–38)	0.88
miRNA profile
Single-miRNA assay	6	0.80 (0.74–0.85)	0.85 (0.78–0.91)	5.4 (3.6–8.0)	0.24 (0.19–0.30)	23 (15–35)	0.88
Two-miRNA assay	9	0.91 (0.86–0.94)	0.87 (0.83–0.90)	7.1 (5.3–9.4)	0.11 (0.07–0.17)	67 (34–131)	0.93
Three-miRNA assay	3	0.93 (0.88–0.95)	0.86 (0.80–0.91)	6.7 (4.6–9.9)	0.09 (0.05–0.14)	79 (39–157)	0.96

The results based on sample specimen demonstrated that plasma showed greater promise as a matrix for miRNA-143 detection compared with urine, with SPE values of 0.87 versus 0.82 and AUC values of 0.89 versus 0.84. Regarding sample size, subgroups representing a large sample size (>100) performed better in diagnosing BCa than those with a small sample size (≤100). The latter group had SEN, SPE and AUC values all around 0.52, significantly lower than the values for the former group. Notably, in a comparison of various miRNA profiles, the corresponding results were as follows: SEN (0.91, 0.93 vs 0.80), SPE (0.87, 0.86 vs 0.85) and AUC (0.93, 0.96 vs 0.88) for miRNA-143 combined with other miRNA assays, miRNA-143 coupled with two other miRNA assays and single-miRNA assays, respectively. Most importantly, as shown in Supplementary Table 2, it was found that miRNA-143 coupled with miRNA-129 displayed the highest values of SEN and SPE at 97%. This suggests that further investigation into the diagnostic value of this miRNA combination is worthwhile, considering only one study has investigated it.

Regarding the diagnostic performance of miRNA-143 in different ethnicities, the authors chose to evaluate the percentage of samples with expression levels of miRNA-143 lower than the cutoff values due to insufficient articles. Interestingly, they observed that the percentage of the Asian population (79.1%) with miRNA-143 expression was slightly higher than that of Caucasians (78.6%), suggesting that miRNA-143 may play a more effective diagnostic role in the Asian ethnicity. This finding is consistent with previous studies but warrants further validation [24].

Additionally, the authors discovered that the combination of miRNA-143 and miRNA-100 had been investigated in three articles to assess its diagnostic value. Consequently, several combined diagnostic parameters were calculated. The combined SEN was found to be 0.88 (95% CI: 0.84–0.92), and the combined SPE was 0.86 (95% CI: 0.80–0.90). Both values showed an I² of 0, indicating promising consistency among these studies. Furthermore, the AUC was 0.95, and the DOR was 45.26, both demonstrating superior diagnostic performance compared with single miRNA-143.

Meta-regression analysis

Based on the information obtained from the forest plot, significant cross-study heterogeneity was observed, prompting the authors to perform a meta-regression analysis to pinpoint the precise sources. Upon scrutinizing Figure 4, it became evident that the specimen type and publication year were the primary contributors to heterogeneity in SPE, whereas variations in SEN primarily resulted from differences in sample size. Furthermore, no significant heterogeneity was detected among the average ages of samples.

Figure 4.

Forest plots of multivariate meta-regression analyses for sensitivity and specificity between bladder cancer patients and a normal control population.

*p < 0.05, **p < 0.01, ***p < 0.001.

Sensitivity analysis

As depicted in Figure 5A & B, the results of the goodness-of-fit analysis and bivariate normality evaluation attest to the robustness of the combined parameters calculated under the random-effects model. Furthermore, no outliers were detected in the influence analysis or evident in the plot of outlier detection analysis (Figure 5C & D), a noteworthy observation.

Figure 5.

Model-checking abilities.

(A) Goodness-of-fit based on level-2 residuals. (B) Bivariate normality. (C) Influence analysis. (D) Detection of outliers.

Publication bias

Furthermore, the authors endeavored to compute the combined SEN and SPE values with each selected study removed individually. The analysis unveiled a remarkable consistency between the final outcomes and the initial findings, underscoring the robustness and reliability of the results. Illustrated in Figure 6, concerns regarding publication bias in the included articles appear to be insignificant in the study (p = 0.51).

Figure 6.

Funnel plot of Deeks' asymmetry test for the six selected articles.

ESS: Explained Sum of Squares.

Clinical utility & index test

The assessment of post-test probabilities for both positive and negative results is widely recognized as one of the effective techniques to evaluate potential clinical diagnostic utility. The results, depicted in Figure 7, hold significance. With a prior probability of 25%, the post-test probability would escalate to 64%, and the positive likelihood ratio would be 5, indicating that a patient with BCa is five-times more likely to receive a positive test result compared with a completely healthy individual. Similarly, with a probability decrease to 7%, the negative likelihood ratio was 0.24, signifying that miRNA-143 serves as an ideal diagnostic indicator of BCa.

Figure 7.

Fagan's nomogram for the clinical utility of miRNA-143 detecting bladder cancer patients.

LR: Likelihood Ratios.

Discussion

With the growing focus on miRNAs, numerous studies have indicated the promising yet inconsistent accuracy of miRNA-143 in diagnosing BCa [^18-23]. This variability may stem from factors such as inadequate sample sizes, variations in screening technologies and differences in diagnostic standards. Therefore, a noteworthy aspect of this study was the utilization of meta-analysis to assess the efficacy of miRNA-143 in detecting BCa in its early stages.

BCa ranks as the second most prevalent urologic tumor globally, predominantly affecting elderly individuals diagnosed with non-muscle-invasive BCa and presenting a lack of curative treatment options [25]. Early detection and intervention are paramount in reducing mortality and enhancing long-term survival rates, underscoring the urgent need for reliable and convenient diagnostic tools in the battle against BCa. Presently, biopsy assisted by cystoscopy stands is the gold standard for BCa diagnosis. However, its invasiveness, discomfort and high risk of sample inaccuracy hinder its widespread clinical adoption [2]. Notably, miRNAs have been widely observed to play a significant role in carcinogenesis processes such as invasion and metastasis [26]. Owing to their specific expression patterns in tumors or serum, oncogenic miRNAs with upregulation or tumor suppressive miRNAs with downregulation hold potential as diagnostic tools for the early detection of various cancer types [27].

miRNA-143, potentially pivotal as a tumor suppressor according to multiple studies, has shown notable downregulation across various solid tumors [^28-30]. Its abnormal expression, coupled with urothelial cell carcinoma development, was predicted to be linked with the FGFR pathway or p53, underscoring the diagnostic potential of miRNA-143 for BCa. This significance is particularly pronounced in non-muscle-invasive BCa, where miRNA-143 demonstrates more specific alterations [31].

The significant decrease in miR-143 levels detected in the urine or plasma of BCa patients highlights its potential as a promising diagnostic tool for BCa [32]. A recent meta-analysis conducted by Ye aimed to investigate the potential competency of miRNAs in the early detection of BCa [33]. The results endorsed these molecules as promising diagnostic biomarkers, with an SEN of 82%, an SPE of 81%, and an AUC value of 0.88. Furthermore, among various potential candidates, miR-143 stood out for its excellent diagnostic performance, with an SEN of 79%, an SPE of 87% and an AUC value also at 0.88.

Based on these findings and hypotheses, the authors specifically opted to conduct a meta-analysis to assess the accuracy of miRNA-143 for the early detection of BCa. Their analysis yielded a combined SEN of 0.80 and combined SPE of 0.85 from six eligible studies, primarily probing the diagnostic significance of miRNA-143 in early BCa screening. These results underscore its promising potential for early detection, consistent with a previous study [33]. Additionally, the AUC value (0.88) and DOR of 23 indicate that miRNA-143 performs well as a diagnostic test.

This systematic meta-analysis revealed several valuable findings. First, multiple-miRNA assays have demonstrated superior diagnostic capability compared with single miRNA-143 assays, particularly in terms of significantly varied values of SPE. This suggests that different types of tumors may require different diagnostic approaches [34]. The rationale behind this is that when multiple miRNAs are involved in the complex molecular mechanisms underlying the development and progression of neoplasms, a more reliable diagnostic network can be established [35]. Furthermore, it is worth noting that the majority of tumors are closely associated with multiple miRNAs rather than a single miRNA, highlighting the limitations of single-miRNA diagnostic methods [34]. In several studies exploring various miRNA panels, combining miRNA-143 with miRNA-100 exhibited a more promising diagnostic performance (SEN: 0.88; SPE: 0.86) compared with using only miRNA-143. Notably, there is a lack of included studies investigating the combination of miRNA-143 and miRNA-129, which displayed the highest values for both SEN (0.97) and SPE (0.97). Further investigation into this combination is warranted.

Second, plasma may be a more suitable medium for screening miRNA-143 to diagnose BCa compared with urine. According to several studies, this could be attributed to specific proteins in plasma that are involved in the isolation of miRNAs, making early detection of BCa using miRNA-143 more accurate and accessible [36]. Moreover, there was a significant difference in diagnostic performance between small sample sizes (≤100) and large sample sizes (>100), with the latter showing more promise.

Additionally, although the authors lacked sufficient studies to conduct a subgroup analysis on the potential variation in diagnostic performance based on different ethnicities, considering the significant downregulation of miRNA-143 in BCa patients, they attempted to calculate the percentage of samples with an expression level of miRNA-143 lower than the cutoff value to investigate its potential diagnostic usage among these two ethnicities. Finally, it might be concluded that miRNA-143 holds greater potential for diagnostic usage among the Asian population compared with Caucasian ethnicity, which aligns with numerous earlier research findings [33,35]. The assumed causes of differences based on ethnicity were related to living circumstances and genetic factors. Specifically, the preference for diagnosing based on ethnicities might be attributed to single nucleotide polymorphisms in the 3′-untranslated region of PAI1 [37]. In detail, it was reported that miRNA-143-3p has a higher binding affinity with the 3′-untranslated region of PAI1 in the wild-type compared with the rs1050813 type, which might retain more miRNA-143-3p in cells and result in lower concentrations within plasma and urine samples. Additionally, the rs1050813 type was found to be strongly associated with the Caucasian population rather than the Asian population, meaning Asians are more likely to have lower levels of miRNA-143 in plasma or urine compared with Caucasians [38]. Since the diagnostic utility of miRNA-143 was based on its significant downregulation among BCa patients, it can be concluded that miRNA-143 has more diagnostic potential among the Asian population, to some extent. Nevertheless, more studies involving other races are needed to validate this hypothesis.

It is important to note a few restrictions on this investigation. First, the overall number of selected articles and studies in Africa and the Caucasus fell short of expectations. This may introduce undesirable outcomes due to ethnicity bias and other factors. However, the quality and sample size of each included study are sufficient to support the above conclusions, and supplementary meta-analysis is warranted in the future. There are debates regarding the number of selected articles required for a valuable meta-analysis. Statistically, only two values are needed to calculate an arithmetic mean, so a minimum of two studies is necessary to conduct a meta-analysis. Studies with a limited number of included articles, like this one, are referred to as ‘mini-meta’, and their scientific value is widely discussed [39]. Nevertheless, one of the key considerations in this type of study is the need to draw conclusions cautiously even if values have been confirmed widely. Second, it is essential to identify panels of miRNAs that can effectively distinguish a specific cancer from other diseases with similar symptoms. However, the present study was limited to detecting BCa patients from healthy controls. Complementary meta-analysis is warranted, especially regarding the ability to distinguish BCa from other, similar diseases using miRNA-143. Third, significant heterogeneity was observed due to sample size, specimen and publication year. Common confounding factors such as gender distribution, family history of cancers and unhealthy lifestyle (smoking and alcohol) may also influence the results. However, these factors were not further investigated in this study due to limited data of included articles. Furthermore, existing methods for quantification of miRNAs such as quantitative reverse-transcription PCR and northern blotting have significant drawbacks that hinder their wide clinical application, such as being time-consuming and requiring sophisticated equipment [40]. Currently, there is no conventional and universally accepted method worldwide. Hence, it is important to establish a standardized quantification method for miRNA-143 to reduce the cross-study bias resulting from procedural heterogeneity. Moreover, the authors found another article reporting that miRNA-143 is a potential biomarker capable of discriminating non-MIBC patients from MIBC ones [41], and all case groups in the selected studies comprised both MIBC and non-MIBC BCa patients. However, there is a lack of details to conduct another subgroup analysis based on the type of BCa. This aspect warrants further investigation. Despite these limitations, it is valuable to recognize the significance of this study, as it pioneers the evaluation of miRNA-143's potential in early BCa detection.

Conclusion

Based on a thorough analysis of relevant articles in BCa, our study has discovered that miRNA-143 in plasma, when assessed using multiple-miRNA assays, can significantly contribute to the early detection of BCa as a noninvasive diagnostic tool. Among various panels of miRNAs, the combination of miRNA-143 and miRNA-100 exhibits slightly superior diagnostic capabilities for BCa compared with using only miRNA-143. In summary, our study extensively examines the diagnostic potential of miRNA-143 and validates previous findings. Additionally, this study offers new insights into maximizing the utility of miRNA-143 in detecting BCa. However, further prospective trials are needed to establish the true diagnostic value of miRNA-143 for BCa.

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2023-0922

Author contributions

All authors contributed to the study's conception and design in some way. Material preparation, data collection and analysis were performed by J Li and H Li. The first draft of the manuscript was written by J Li and Y Yang and S Yu was responsible for polishing the whole passage. J Ye was corresponding author who also gave some instructions during the preparation of the article. All authors read and approved the final manuscript.

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, stock ownership or options and expert testimony.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.