Clinical Biochemical Significance of STAT6, ERG, and miR-647 Expression in Prostate Cancer: Associations With Tumor Aggressiveness and Patient Prognosis
STAT6, ERG, and miR-647 in Prostate Cancer
Abstract
Background: Reliable molecular indicators that can facilitate early detection and prognosis prediction in prostate cancer are still insufficient. Although Transcription 6 (STAT6), ERG, and microRNA-647 (miR-647) have recently been recognized as key participants in tumor-related signaling pathways, their specific biochemical functions in the context of prostate cancer have yet to be clearly defined. This study evaluated the expression profiles of STAT6 mRNA, ERG mRNA, and miR-647 in prostate cancer tissue and explored their associations with clinicopathological features and patient outcomes.
Methods: Surgical specimens were obtained from 70 patients, including both prostate cancer tissues and their corresponding adjacent non-tumorous counterparts. Quantitative real-time PCR (qPCR) was used to measure STAT6 mRNA, ERG mRNA, and miR-647 expression. The relationships between biomarker expression and clinical parameters—including age, tumor diameter, lymph node involvement, T stage, and pathological differentiation—were examined. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan–Meier curves with log-rank comparisons, while Spearman correlation analysis was employed to determine the associations among the examined molecular markers.
Results: Levels of STAT6 mRNA, ERG mRNA, and miR-647 were markedly higher in prostate cancer specimens than in the paired non-tumorous tissues (P<0.05). Elevated expression of these molecules corresponded to the presence of lymph node metastasis, higher T stage, and unfavorable histological differentiation, whereas no significant associations were observed with patient age or tumor dimensions. Patients with high STAT6, ERG, or miR-647 expression exhibited significantly reduced OS and PFS compared with low-expression groups (all P<0.05). miR-647 expression positively correlated with STAT6 mRNA (r=0.867) and ERG mRNA (r=0.724) (P<0.05).
Conclusion: STAT6, ERG, and miR-647 exhibit pronounced overexpression in prostate cancer, and their elevated levels are closely linked to more aggressive tumor behavior and unfavorable clinical outcomes. Their coordinated dysregulation suggests a potential molecular axis involved in prostate cancer progression. These molecular indicators have the potential to enhance biochemical risk stratification and support more refined molecular assessments in routine clinical settings.
References
2. Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, et al. EAU guidelines on prostate cancer. Part II: Treatment of advanced, relapsing, and castration-resistant prostate cancer. Eur Urol 2014; 65(2): 467-79.
3. Gorchakov AA, Kulemzin SV, Kochneva GV, Taranin AV. Challenges and Prospects of Chimeric Antigen Receptor T-cell Therapy for Metastatic Prostate Cancer. Eur Urol 2020; 77(3): 299-308.
4. Sekhoacha M, Riet K, Motloung P, Gumenku L, Adegoke A, Mashele S. Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches. Molecules 2022; 27(17):
5. Yu YD, Kim TJ. Chimeric Antigen Receptor-Engineered T Cell Therapy for the Management of Patients with Metastatic Prostate Cancer: A Comprehensive Review. Int J Mol Sci 2021; 22(2):
6. Huang H, Liu Y, Wen Z, Chen C, Wang C, Li H, et al. Gut microbiota in patients with prostate cancer: a systematic review and meta-analysis. Bmc Cancer 2024; 24(1): 261.
7. Boyiadzis MM, Dhodapkar MV, Brentjens RJ, Kochenderfer JN, Neelapu SS, Maus MV, et al. Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance. J Immunother Cancer 2018; 6(1): 137.
8. Litwin MS, Tan H. The Diagnosis and Treatment of Prostate Cancer: A Review. Jama-J Am Med Assoc 2017; 317(24): 2532-42.
9. Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2017; 71(4): 618-29.
10. Cooley LF, Srivastava A, Shore ND. Updates on Management of Biochemical Recurrent Prostate Cancer. Curr Treat Option On 2024; 25(3): 284-92.
11. Adamaki M, Zoumpourlis V. Prostate Cancer Biomarkers: From diagnosis to prognosis and precision-guided therapeutics. Pharmacol Therapeut 2021; 228: 107932.
12. Roychowdhury S, Chinnaiyan AM. Advancing precision medicine for prostate cancer through genomics. J Clin Oncol 2013; 31(15): 1866-73.
13. Hou Z, Huang S, Mei Z, Chen L, Guo J, Gao Y, et al. Inhibiting 3betaHSD1 to eliminate the oncogenic effects of progesterone in prostate cancer. Cell Rep Med 2022; 3(3): 100561.
14. Elshazly AM, Gewirtz DA. Making the Case for Autophagy Inhibition as a Therapeutic Strategy in Combination with Androgen-Targeted Therapies in Prostate Cancer. Cancers 2023; 15(20):
15. Sedarsky J, Degon M, Srivastava S, Dobi A. Ethnicity and ERG frequency in prostate cancer. Nat Rev Urol 2018; 15(2): 125-31.
16. Rafikova G, Gilyazova I, Enikeeva K, Pavlov V, Kzhyshkowska J. Prostate Cancer: Genetics, Epigenetics and the Need for Immunological Biomarkers. Int J Mol Sci 2023; 24(16):
17. Ateeq B, Bhatia V, Goel S. Molecular Discriminators of Racial Disparities in Prostate Cancer. Trends Cancer 2016; 2(3): 116-20.
18. Zeng J, Chen J, Li M, Zhong C, Liu Z, Wang Y, et al. Integrated high-throughput analysis identifies super enhancers in metastatic castration-resistant prostate cancer. Front Pharmacol 2023; 14: 1191129.
19. Zhou CK, Young D, Yeboah ED, Coburn SB, Tettey Y, Biritwum RB, et al. TMPRSS2:ERG Gene Fusions in Prostate Cancer of West African Men and a Meta-Analysis of Racial Differences. Am J Epidemiol 2017; 186(12): 1352-61.
20. Koide H, Kimura T, Inaba H, Sato S, Iwatani K, Yorozu T, et al. Comparison of ERG and SPINK1 expression among incidental and metastatic prostate cancer in Japanese men. Prostate 2019; 79(1): 3-8.
Copyright (c) 2026 Xin Hong, Lin Zhao, Tian Wang, Xiaobing Yang, Changzhen Hao

This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
