Skip to main content
NCBI home page
Evidence-based Complementary and Alternative Medicine : eCAM logoLink to Evidence-based Complementary and Alternative Medicine : eCAM
. 2022 Apr 15;2022:1116535. doi: 10.1155/2022/1116535

Role of STAT3 Expression in Thyroid Cancer: A Meta-Analysis and Systematic Review Based on the Chinese Population

Ya-Nan Liang 1, Zuwang Zhang 2,✉, Ji Song 1, Fuwei Yang 1, Pan Yang 3
PMCID: PMC9033348  PMID: 35463085

Abstract

Background

Signal transduction and activator of transcription 3 (STAT3) is an oncogene with transcriptional activity. In recent years, there have been several studies concerning the clinicopathological significance of the expression of the STAT3 protein in thyroid cancer. However, the results are still inconsistent. In this study, we conducted a meta-analysis to evaluate the relationship between the expression of STAT3 protein and thyroid cancer susceptibility and its clinicopathological characteristics.

Methods

We searched the China National Knowledge Infrastructure (CNKI) database, Chinese Biomedical Literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wanfang, PubMed, and EMBASE. The time frame of the publication search was from the establishment of each of the databases until December 2021. We performed a meta-analysis to quantitatively evaluate the relationship between the expression of the STAT3 protein in thyroid cancer and its clinicopathological characteristics.

Results

A total of eight articles were included in the meta-analysis, covering 448 thyroid cancer patients and 227 controls. Results indicated that the expression of STAT3 protein in thyroid cancer tissue is highly expressed (OR = 14.41, 95% CI (6.94, 29.91), p < 0.001). Besides, we also discovered that STAT3 protein is negatively correlated with thyroid cancer tumor diameter and TNM stage (OR = 0.13, 95% CI (0.05, 0.33), p < 0.001; OR = 0.40, 95% CI (0.24, 0.67), p < 0.001) and positively correlated with lymph node metastasis (OR = 2.83, 95% CI (1.08, 7.46), p = 0.035). However, STAT3 expression is not related to gender (OR = 0.88, 95% CI (0.54, 1.44), p = 0.609), age (OR = 0.54, 95% CI (0.21, 1.36), p = 0.191), capsular invasion (OR = 2.98, 95% CI (0.23, 38.29), p = 0.403), or tumor multiplicity (OR = 0.25, 95% CI (0.003, 19.28), p = 0.533).

Conclusions

This study reveals that STAT3 protein expression is significantly related to the susceptibility and clinicopathological characteristics of thyroid cancer. It also suggests that STAT3 may be a potential predictor of the clinical progression of thyroid cancer.

1. Introduction

Thyroid cancer is the most common tumor in the endocrine system, and its incidence rate is gradually increasing [1, 2], yet its pathogenesis is still not clear. Approximately 5–10% of clinically discovered thyroid nodules are thyroid cancer [3]. At present, thyroid cancer is usually clinically diagnosed by thyroid biopsy. However, the lack of early laboratory biochemical indicators has caused certain difficulties in the prevention, timely treatment, and prognosis of its early lymph node metastasis. Therefore, further exploration of markers related to the progression and metastasis of thyroid cancer is of great significance for improving the survival rate of thyroid cancer and guiding its treatment.

Previous studies have located many biomarkers of thyroid cancer, including circulating microRNAs, forkhead box Q1 (FOXQ1), and p53 [4–7]. These biomarkers are all related to the clinicopathology and prognosis of thyroid cancer. Current prognostic indicators include tumor size, location, stage, recurrence rate, and metastasis, but the measurement of these indicators is inaccurate and ineffective. Therefore, it is necessary to find a representative biomarker that can provide a reliable and effective prognosis.

Signal transduction and activator of transcription (STAT) is a family of proteins that regulate cell proliferation, growth, and differentiation and are involved in the signal transduction pathways of various cytokines and growth factors in the body [8, 9]. The STAT family has seven members, of which STAT3 is one of its prominent elements. STAT3 controls many physiological processes including proliferation, differentiation, survival, development, and inflammation. Besides, it is abnormally expressed under certain pathological conditions such as human tumors [10–12]. STAT3 phosphorylates into p-STAT3 under the action of Janus kinase (JAKS), enters the nucleus and binds to specific DNA sequences, regulates the transcription and expression of related target genes, promotes tumor cell proliferation and drug resistance, and inhibits tumor cell apoptosis [12]. Studies have shown that the expression of STAT3 protein is related to poor prognosis of lung cancer [13], breast cancer [14], liver cancer [15], colorectal cancer [16], and prostate cancer [17]. Regarding the relationship between STAT3 and thyroid cancer, existing research has failed to reach a consensus. In this study, meta-analysis was used to clarify the relationship between STAT3 expression and clinicopathological factors in thyroid cancer.

2. Materials and Methods

We conducted this review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Moreover, we have registered this systematic review and meta-analysis in the Open Science Framework (Registration number: DOI 10.17605/OSF.IO/S5DK6).

2.1. Literature Search

Two researchers independently searched the following databases for systematic retrieval: China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific and Journal Database (VIP), Wanfang database, PubMed, and EMBASE. The search period was from the formation of the databases to December 2021. The search keywords were as follows: STAT3 transcription factor, signal transducer and activator of transcription protein 3, STAT3 protein, thyroid neoplasms, thyroid cancer ∗, thyroid carcinoma ∗, thyroid adenoma ∗, and thyroid tumor ∗.

2.2. Selection Criteria

Study inclusion criteria included the following: cohort studies or case-control studies involving STAT3 and thyroid cancer, and the language was limited to Chinese and English; the case group included specimens of patients with postoperative pathological diagnosis of thyroid cancer, while the control group included pathological diagnoses of normal thyroid cancer tissue in or adjacent to the tumor; and detection of expression levels of the STAT3 protein in tissue samples by immunohistochemistry. Exclusion criteria included the following: abstracts, case reports, summaries, and meeting minutes and repeated publications or repeated data.

2.3. Data Extraction

Two researchers independently screened the titles, abstracts, and full texts of the selected articles. In case of disagreements during data extraction, the researchers managed to reach a consensus through discussion. If no agreement could be reached, a third researcher made the final decision. The extracted content mainly included first author, publication time, age, gender, country, language, sample size of the case group and the control group, lymph node metastasis, TNM staging, and research type.

2.4. Quality Assessment

We employed the Newcastle–Ottawa scale (NOS) to evaluate the quality of the included literature. The focus of the evaluation mainly included the selection and determination of the research object, whether the groups were comparable, and the measurement of exposure factors. The highest score on the scale is 9 points, and studies with scores greater than 6 are considered high-quality articles [13–15]. Two researchers independently calculated the NOS scores, and they achieved consistency.

2.5. Statistical Analysis

For this meta-analysis, we utilized Stata 14.0 software. Moreover, we applied odds ratios (OR) and 95% confidence intervals (CIs) to evaluate the impact of STAT3 expression on clinicopathological characteristics. Also, we analyzed the heterogeneity of the included studies using the P value and I2. In the results, if P < 0.1, I2 > 50%, and there is a certain statistical heterogeneity between the studies, then we performed the meta-analysis using a random model; however, if P > 0.1, I2 < 50%, and the possibility of heterogeneity between the studies was small, then we used a fixed model for the meta-analysis. Finally, we conducted a sensitivity analysis on the included studies. We used Egger's test and Bagger's test to determine the possibility of publication bias. Here, P < 0.05 indicated that the difference was statistically significant.

3. Results

3.1. Literature Search Results

The eight included articles [25–32] were published between 2010 and 2017 in China, and all were case-control studies. Figure 1 shows a flowchart of the literature screening process. All eight articles reported on the expression of STAT3 in thyroid cancer tissue and normal thyroid tissue. Six reports described the relationship between STAT3 expression in thyroid cancer tissue and lymph node metastasis, while three reported the relationship between STAT3 expression in thyroid cancer tissue and tumor TNM staging. Also, four articles explained the relationship between the expression of STAT3 in thyroid cancer tissue and age and gender. Table 1 provides specific information from the included literature.

Figure 1.

Figure 1

Open in a new tab

Flow diagram showing the literature filtration process.

Table 1.

Characteristics and quality score of the studies.

Study Country Ethnicity Detection method Cutoff value (%) Antibody supplier STAT3 (±) Quality
Case Control
Li et al., 2015 China Asian IHC >10 Abgent, San Diego, CA, USA 32/10 8/12 7
Zhang et al., 2016 China Asian IHC >5 Santa Cruz Biotechnology, Inc 31/0 5/26 7
Zhang et al., 2013 China Asian IHC >10 Santa Cruz Biotechnology, Inc 44/12 8/16 7
Li et al., 2010 China Asian IHC >10 BOSTER Biological Technology Co., Ltd. 23/19 2/13 6
Wang, 2013 China Asian IHC >10 Santa Cruz Biotechnology, Inc 66/24 2/28 7
Zhang et al., 2011 China Asian IHC >10 NA 40/1 11/24 6
Huang, 2015 China Asian IHC >10 NA 73/13 3/9 7
Xu, 2017 China Asian IHC >5 BOSTER Biological Technology Co., Ltd. 47/13 17/43 7
Open in a new tab

NA, data not available.

3.2. Association between STAT3 Expression and the Clinicopathological Parameters of Thyroid Cancer

The eight articles [16–23] contained data from 448 thyroid cancer patients and 227 healthy controls. Results suggested that compared with normal tissue, the expression of STAT3 in thyroid cancer tissue is highly expressed (Figure 2) (OR = 14.41, 95% CI (6.94, 29.91), p < 0.001). Besides, we also found that STAT3 is negatively correlated with thyroid cancer tumor diameter and TNM stage (OR = 0.13, 95% CI (0.05, 0.33), p < 0.001; OR = 0.40, 95% CI (0.24, 0.67), p < 0.001), but positively correlated with lymph node metastasis (OR = 2.83, 95% CI (1.08, 7.46), p = 0.035). The expression of STAT3 is not related to gender (OR = 0.88, 95% CI (0.54, 1.44), p = 0.609), age (OR = 0.54, 95% CI (0.21, 1.36), p = 0.191), capsular invasion (OR = 2.98, 95% CI (0.23, 38.29), p = 0.403), or tumor multiplicity (OR = 0.25, 95% CI (0.003, 19.28), p = 0.533) (Table 2).

Figure 2.

Figure 2

Open in a new tab

Forest plot showing the relationship between STAT3 protein expression and thyroid cancer.

Table 2.

Association between STAT3 expression and clinical features of thyroid cancer patients in meta-analysis.

Factors Studies (n) Analytical model OR (95%CI) P value Heterogeneity
I 2 P h
Age (<45 vs ≥ 45) 4 REM 0.54 (0.21, 1.36) 0.191 64.00 0.039
Sex (male vs female) 4 FEM 0.88 (0.54, 1.44) 0.609 0 0.898
Tumor size (≤1 cm vs. > 1 cm) 2 FEM 0.13 (0.05, 0.33) <0.001 0 0.743
Tumor metastasis (yes vs. no) 6 REM 2.83 (1.08, 7.46) 0.035 80.70 <0.001
Capsular invasion (yes vs. no) 2 REM 2.98 (0.23, 38.29) 0.403 89.60 0.002
TNM stage (I-II vs. III-IV) 3 REM 0.40 (0.24, 0.67) <0.001 82.10 0.004
Tumor multiplicity (single vs. multiplicity) 2 REM 0.25 (0.003, 19.28) 0.533 86.00 0.008
Open in a new tab

P values were obtained by using the “METAN” program in Stata 14.0; P value 0.05 was considered as statistically significant. FEM, fixed-effects model; REM, random-effects model; TNM, tumor node metastasis; OR, odds ratio; CI, confidence interval. Bold fonts indicate statistical differences.

3.3. Subgroup Analysis

We performed a subgroup analysis based on the cutoff value (>10% vs. > 5%). When the cutoff value is greater than 10%, the expression of STAT3 in thyroid cancer tissue is more highly expressed than normal tissue (OR = 13.10, 95% CI (5.85, 29.40), p < 0.0001). At the same time, when the cutoff value is set to >5%, compared with normal tissue, the expression of STAT3 in thyroid cancer tissue is also highly expressed (OR = 40.27, 95% CI (1.15, 1412.99), p = 0.042) (Figure 3).

Figure 3.

Figure 3

Open in a new tab

Forest plot for subgroup analysis.

3.4. Publication Bias

For the analysis of STAT3 expression in thyroid cancer tissue and normal tissue, we conducted a sensitivity analysis and publication bias detection. The results suggested no publication bias (Begg's test: p = 0.260, Egger's test: p = 0.532), as shown in Figure 4.

Figure 4.

Figure 4

Open in a new tab

Funnel plot in the meta-analysis of relationship of STAT3 protein expression and thyroid cancer.

3.5. Sensitivity Analysis

Results from the sensitivity analysis, shown in Figure 5, suggested that no single study had a significant effect on the overall results, indicating that meta-analysis results are stable.

Figure 5.

Figure 5

Open in a new tab

Sensitivity analysis on the relationship of STAT3 protein expression and thyroid cancer.

4. Discussion

Currently, the etiology and pathogenesis of thyroid cancer are not clear, and there is a lack of effective treatment methods. Therefore, it is extremely important to explore the occurrence and development of thyroid cancer by searching for oncogenes related to thyroid cancer. In this study, we used a meta-analysis to systematically evaluate the relationship between STAT3 protein expression and the susceptibility and clinicopathological characteristics of thyroid cancer. Results indicated that high expression levels of STAT3 protein increase the risk of thyroid cancer. Therefore, we hypothesize that STAT3 may be one of the oncogenes of thyroid cancer.

As an oncogene, STAT3 plays a vital role in the development of several forms of cancer. In many human cancers, STAT3 is continuously activated, and the phosphorylation of specific tyrosine residue is an important step in STAT3 activation. Once activated, p-STAT3 induces the expression of a variety of genes involved in cell survival, proliferation, migration, invasion, angiogenesis, and immune escape, thus promoting carcinogenic transformation. By inhibiting STAT3 phosphorylation and p-STAT3-mediated DNA transcription and replication, it can promote tumor cell apoptosis [24]. However, established opinions on the tumor-promoting effects of STAT3 have been frequently challenged. Banerjee et al. [25] found that STAT3 has a dual role in breast cancer since STAT3 promotes breast cancer under certain conditions, but it may also be a negative regulator of certain types of breast cancer.

Grabner et al. [26] confirmed that STAT3 has an antitumor effect in mice with lung cancer. The study of STAT3-promoting thyroid carcinogenesis poses similar challenges. The study of Couto et al. [27] revealed that STAT3 is an inhibitor of thyroid tumor growth in preclinical models. Besides, the study of Kim et al. [28] concluded that the activity of STAT3 in papillary thyroid carcinoma tissue is reduced. However, it remains to be explored whether the STAT3 negative regulation of thyroid cancer applies to all histological subtypes, thyroid cancer staging, and distant metastasis progression. Contrary to the research of Couto [27] and Kim et al. [28], we ascertained that STAT3 is highly expressed in thyroid cancer tissue. Also, STAT3 expression increases in thyroid cancer tissue with the metastasis of thyroid cancer lymph nodes or an increase in TNM staging, which subsequently promotes the occurrence and development of thyroid cancer.

Since most patients with thyroid cancer have a good prognosis after surgery, the recurrence rate is low. Even if cancer recurs, the mortality rate remains low. Thus, it is difficult to evaluate the prognosis of patients by survival time only. Therefore, many scholars use clinicopathological characteristics as prognostic indicators, such as gender, age, tumor size, lymph node metastasis, distant metastasis, tissue subtype, and clinical stage [29–34]. This meta-analysis demonstrated that STAT3 is related to the diameter of thyroid cancer tumors, TNM staging, and lymph node metastasis. As a result, the expression of STAT3 protein can be used as an indicator of the prognosis of patients with thyroid cancer.

This study has some limitations. First, the literature included in the meta-analysis lacks survival analysis data. Thus, it is impossible to further evaluate the influence of STAT3 protein on the prognosis of patients with thyroid cancer. Consequently, we can only explain the effect of STAT3 protein expression on survival from pathological characteristics. Because the treatment methods for patients in this study varied, there may be a certain impact on the results. None of the patients included in the meta-analysis received any treatment before surgery, and all patients were treated with surgical resection. Besides, the patients included in this study are only from Asia. The level of medical development in different regions may also affect the results, and different experimental methods may have been used to detect the expression of STAT3.

In summary, our meta-analysis systematically analyzed the relationship between STAT3 protein and thyroid cancer susceptibility and clinical progression. Based on the collected data, we established that STAT3 protein expression is strongly related to thyroid cancer susceptibility, lymph node metastasis, tumor size, and TNM stage. Thus, the expression of STAT3 protein has reference significance for the early diagnosis, treatment, and prevention of thyroid cancer. However, considering the limitations of this study, we require larger study populations, clinical information, multicenter design, and high-quality studies to verify these findings.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

References

  • 1.Bergdorf K. N., Ferguson D. C., Mehrad M., Ely K., Weiss V. L. Papillary thyroid carcinoma behavior: clues in the tumor microenvironment. Endocrine-Related Cancer . 2019;26(6):601–614. doi: 10.1530/ERC-19-0074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Gao X., Wang J., Zhang S. Integrated bioinformatics analysis of hub genes and pathways in anaplastic thyroid carcinomas. International Journal of Endocrinology . 2019;2019:1–9. doi: 10.1155/2019/9651380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Hegedüs L. The thyroid nodule. New England Journal of Medicine . 2022;351(11):1265–1268. [Google Scholar]
  • 4.Li Y., Wang H. Q., Wang A. C. Overexpression of Forkhead box Q1 correlates with poor prognosis in papillary thyroid carcinoma. Clinical Endocrinology . 2019;90(2):334–342. doi: 10.1111/cen.13896. [DOI] [PubMed] [Google Scholar]
  • 5.Perdas E., Stawski R., Nowak D., Zubrzycka M. Potential of liquid biopsy in papillary thyroid carcinoma in context of miRNA, BRAF and p53 mutation. Current Drug Targets . 2018;19(14):1721–1729. doi: 10.2174/1389450119666180226124349. [DOI] [PubMed] [Google Scholar]
  • 6.Jing W., Li X., Peng R. The diagnostic and prognostic significance of long noncoding RNAs expression in thyroid cancer: a systematic review and meta-analysis. Pathology, Research & Practice . 2018;214(3):327–334. doi: 10.1016/j.prp.2018.01.008. [DOI] [PubMed] [Google Scholar]
  • 7.Pak K., Suh S., Kim S. J., Kim I. J. Prognostic value of genetic mutations in thyroid cancer: a meta-analysis. Thyroid . 2015;25(1):63–70. doi: 10.1089/thy.2014.0241. [DOI] [PubMed] [Google Scholar]
  • 8.Lin X. M., Chen H., Zhan X. L. MiR-203 regulates JAK-STAT pathway in affecting pancreatic cancer cells proliferation and apoptosis by targeting SOCS3. European Review for Medical and Pharmacological Sciences . 2019;23(16):6906–6913. doi: 10.26355/eurrev_201908_18730. [DOI] [PubMed] [Google Scholar]
  • 9.Kim C., Lee S. G., Yang W. M. Formononetin-induced oxidative stress abrogates the activation of STAT3/5 signaling axis and suppresses the tumor growth in multiple myeloma preclinical model. Cancer Letters . 2018;431:123–141. doi: 10.1016/j.canlet.2018.05.038. [DOI] [PubMed] [Google Scholar]
  • 10.Cao Y., Wang J., Tian H., Fu G. H. Mitochondrial ROS accumulation inhibiting JAK2/STAT3 pathway is a critical modulator of CYT997-induced autophagy and apoptosis in gastric cancer. Journal of Experimental & Clinical Cancer Research . 2020;39(1):1–15. doi: 10.1186/s13046-020-01621-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Ashrafizadeh M., Zarrabi A., Orouei S. STAT3 pathway in gastric cancer: signaling, therapeutic targeting and future prospects. Biology . 2020;9(6):1–36. doi: 10.3390/biology9060126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Qi Q.-R., Yang Z.-M. Regulation and function of signal transducer and activator of transcription 3. World Journal of Biological Chemistry . 2014;5(2):231–239. doi: 10.4331/wjbc.v5.i2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Lo C. K., Mertz D., Loeb M. Newcastle-Ottawa Scale: comparing reviewers’ to authors’ assessments. BMC Medical Research Methodology . 2014;14(1):p. 45. doi: 10.1186/1471-2288-14-45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. European Journal of Epidemiology . 2010;25(9):603–605. doi: 10.1007/s10654-010-9491-z. [DOI] [PubMed] [Google Scholar]
  • 15.Wei S., Chen M., Chen N., Liu L. Feasibility and safety of robot-assisted thoracic surgery for lung lobectomy in patients with non-small cell lung cancer: a systematic review and meta-analysis. World Journal of Surgical Oncology . 2017;15(1):p. 98. doi: 10.1186/s12957-017-1168-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Huang J., Su R. Expression of S100A4 and signal transducer and activator of transcription 3 in thyroid carcinoma and thyroid benign tumor and clinical significance. Chinese Journal of Experimental Surgery . 2017;32(005):1144–1146. [Google Scholar]
  • 17.Li Z., Lang X. O., Zhang S. J., Jiang W. H. Expressions of Stat3 and Stat5 in differentiated thyroid carcinoma tissues and significances. Journal of Jilin University - Medicine Edition . 2014;36(4):708–712. [Google Scholar]
  • 18.Wang Y., Jiang W., Zhu C. Expressions of STAT3 and VEGF-C in thyroid carcinoma and their relationship with clinicopathological characteristics. Journal of Chinese Oncology . 2015;19(2):118–121. [Google Scholar]
  • 19.Xu Y., Li H., Chunxia S. Expression of Stat3,Survivin,MMP-13 in thyroid carcinoma and its effect on lymph node metastasis. Shandong Journal of Traditional Chinese Medicine . 2013;57(045):74–76. [Google Scholar]
  • 20.Li Y., Li L., Li Q. Expression of signal transducer and activator of transcription 3 and its phosphorylated form is significantly upregulated in patients with papillary thyroid cancer. Experimental and Therapeutic Medicine . 2015;9(6):2195–2201. doi: 10.3892/etm.2015.2409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Zhang C., Li Y., Wu J. Clinical significance of STAT3, pSTAT3 and TFF3 in human papillary thyroid carcinoma. Modern Preventive Medicine . 2016;43(1):182–186. [Google Scholar]
  • 22.Zhang J., Gill A., Atmore B., Johns A., Mcmullen T. Upregulation of the signal transducers and activators of transcription 3 (STAT3) pathway in lymphatic metastases of papillary thyroid cancer. International Journal of Clinical and Experimental Pathology . 2011;4(4):356–362. [PMC free article] [PubMed] [Google Scholar]
  • 23.Zhang Z., Bai Y., Li P. [Relationship between activated STAT3 protein and epithelial-mesenchymal transition in papillary thyroid carcinoma] Journal of clinical otorhinolaryngology, head, and neck surgery . 2013;27(22):1265–1268. [PubMed] [Google Scholar]
  • 24.Huang W., Dong Z., Chen Y. Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo. Oncogene . 2016;35(6):p. 802. doi: 10.1038/onc.2015.419. [DOI] [PubMed] [Google Scholar]
  • 25.Banerjee K., Pru C., Pru J. K., Resat H. STAT3 knockdown induces tumor formation by MDA-MB-231 cells. Clin Oncol Res . 2018;1(1):1–16. doi: 10.31487/j.COR.2018.10.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Grabner B., Schramek D., Mueller K. M. Disruption of STAT3 signalling promotes KRAS-induced lung tumorigenesis. Nature Communications . 2021;6:1–14. doi: 10.1038/ncomms7285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Couto J. P., Daly L., Almeida A. STAT3 negatively regulates thyroid tumorigenesis. Proceedings of the National Academy of Sciences of the U S A . 2012;109(35):1–10. doi: 10.1073/pnas.1201232109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Kim W. G., Choi H. J., Kim W. B. Basal STAT3 activities are negatively correlated with tumor size in papillary thyroid carcinomas. Journal of Endocrinological Investigation . 2012;35(4):413–418. doi: 10.3275/7907. [DOI] [PubMed] [Google Scholar]
  • 29.Kebebew E., Weng J., Bauer J. The prevalence and prognostic value of BRAF mutation in thyroid cancer. Annals of Surgery . 2007;246(3):466–471. doi: 10.1097/SLA.0b013e318148563d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Mazzaferri E. L., Jhiang S. M. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. The American Journal of Medicine . 1994;97(5):418–428. doi: 10.1016/0002-9343(94)90321-2. [DOI] [PubMed] [Google Scholar]
  • 31.Sherman S. I., Brierley J. D., Sperling M. Prospective multicenter study of thyroiscarcinoma treatment: initial analysis of staging and outcome. National Thyroid Cancer Treatment Cooperative Study Registry Group. Cancer . 1998;83(5):1012–1021. doi: 10.1002/(sici)1097-0142(19980901)83:5<1012::aid-cncr28>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  • 32.Xing M. BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications. Endocrine Reviews . 2007;28(7):742–762. doi: 10.1210/er.2007-0007. [DOI] [PubMed] [Google Scholar]
  • 33.Leboulleux S., Rubino C., Baudin E. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. The Journal of Cinical Endocrinology and Metabolism . 2005;90(10):5723–5729. doi: 10.1210/jc.2005-0285. [DOI] [PubMed] [Google Scholar]
  • 34.Lupi C., Giannini R., Ugolini C. Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. The Journal of Cinical Endocrinology and Metabolism . 2007;92(11):4085–4090. doi: 10.1210/jc.2007-1179. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data used to support the findings of this study are available from the corresponding author upon request.

Articles from Evidence-based Complementary and Alternative Medicine : eCAM are provided here courtesy of Wiley

RESOURCES