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The Association of Androgen Receptor Expression with Renal Cell Carcinoma Risk: a Systematic Review and Meta-Analysis

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Pathology & Oncology Research

Abstract

The relationship between androgen receptor expression and renal cell carcinoma risk remains controversial. This study is aimed to investigate the clinical significance of androgen receptor expression in renal cell carcinoma. A computerized bibliographic search of Embase, the PubMed, and Web of Science combined with manual research between 1977 and 2017 was conducted to explore the association between androgen receptor expression and clinicopathological features of renal cell carcinoma. Data were analyzed by a meta-analysis using RevMan 5.3 analysis software. Eleven retrospective studies with 1839 renal cell carcinoma cases were finally included according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. It was found that there was no significant difference between androgen receptor expression and susceptibility, pathological type, metastatic status, metastatic type (lymph or distant metastasis) and cancer-specific survival of renal cell carcinoma (P > 0.05). However, positive androgen receptor expression was demonstrated to be significantly associated with male patients, lower pathological grade, and earlier tumor stage of renal cell carcinoma (OR = 1.69, 95% CI = 1.30–2.19, P < 0.0001; OR = 2.06, 95% CI = 1.49–2.85, P < 0.0001; OR = 2.81, 95% CI = 1.30–6.12, P = 0.009; respectively). In conclusion, higher androgen receptor expression was correlated with male patients, low tumor grade and early stage of renal cell carcinoma. Based on current results, androgen receptor-inhibited target therapy for renal cell carcinoma patients may be of limited benefits and should be taken into more evaluations.

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Data Availability

All data were extracted from the articles cited in this manuscript.

Abbreviations

AR:

Androgen receptor

ccRCC:

Clear cell RCC

CI:

Confidential interval

CSS:

cancer-specific survival

DCC:

Dextran-coated charcoal

HIF:

Hypoxia-induced factor

IHC:

Immunohistochemistry

mTOR:

Mammalian target of rapamycin

NA:

Not available

OR:

Odds ratio

PCR:

Polymerase chain reaction

PDGF:

Platelet-derived growth factor

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-analyses

pT:

pathological T

RCC:

Renal cell carcinoma

VEGF:

Vascular endothelial growth factor

WB:

Western blot

References

  1. Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    Article  PubMed  Google Scholar 

  2. Campbell S, Uzzo RG, Allaf ME, Bass EB, Cadeddu JA, Chang A, Clark PE, Davis BJ, Derweesh IH, Giambarresi L, Gervais DA, Hu SL, Lane BR, Leibovich BC, Pierorazio PM (2017) Renal mass and localized renal Cancer: AUA guideline. J Urol 198:520–529

    Article  PubMed  Google Scholar 

  3. Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, Egevad L, Algaba F, Moch H, Grignon DJ, Montironi R, Srigley JR, Members of the ISUP Renal Tumor Panel (2013) The International Society of Urological Pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 37:1490–1504

    Article  PubMed  Google Scholar 

  4. Kuthi L, Jenei A, Hajdu A, Németh I, Varga Z, Bajory Z, Pajor L, Iványi B (2017) Prognostic factors for renal cell carcinoma subtypes diagnosed according to the 2016 WHO renal tumor classification: a study involving 928 patients. Pathol Oncol Res 23:689–698

    Article  PubMed  Google Scholar 

  5. He D, Li L, Zhu G, Liang L, Guan Z, Chang L, Chen Y, Yeh S, Chang C (2014) ASC-J9 suppresses renal cell carcinoma progression by targeting an androgen receptor-dependent HIF2α/VEGF signaling pathway. Cancer Res 74:4420–4430

    Article  CAS  PubMed  Google Scholar 

  6. Zhang HL, Sheng XN, Li XS, Wang HK, Chi ZH, He ZS, Ye DW, Guo J (2017) Sorafenib versus sunitinib as first-line treatment agents in Chinese patients with metastatic renal cell carcinoma: the largest multicenter retrospective analysis of survival and prognostic factors. BMC Cancer 17:16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Chiarini F, Evangelisti C, McCubrey JA, Martelli AM (2015) Current treatment strategies for inhibiting mTOR in cancer. Trends Pharmacol Sci 36:124–135

    Article  CAS  PubMed  Google Scholar 

  8. Ciccarese C, Brunelli M, Montironi R, Fiorentino M, Iacovelli R, Heng D, Tortora G, Massari F (2016) The prospect of precision therapy for renal cell carcinoma. Cancer Treat Rev 49:37–44

    Article  CAS  PubMed  Google Scholar 

  9. Ravaud A, Motzer RJ, Pandha HS, George DJ, Pantuck AJ, Patel A, Chang YH, Escudier B, Donskov F, Magheli A, Carteni G, Laguerre B, Tomczak P, Breza J, Gerletti P, Lechuga M, Lin X, Martini JF, Ramaswamy K, Casey M, Staehler M, Patard JJ, S-TRAC Investigators (2016) Adjuvant Sunitinib in high-risk renal-cell carcinoma after nephrectomy. N Engl J Med 375:2246–2254

    Article  CAS  PubMed  Google Scholar 

  10. Matsumoto T, Sakari M, Okada M, Yokoyama A, Takahashi S, Kouzmenko A, Kato S (2013) The androgen receptor in health and disease. Annu Rev Physiol 75:201–224

    Article  CAS  PubMed  Google Scholar 

  11. Pihlajamaa P, Sahu B, Janne OA (2015) Determinants of receptor- and tissue-specific actions in androgen signaling. Endocr Rev 36:357–384

    Article  CAS  PubMed  Google Scholar 

  12. Bennett NC, Gardiner RA, Hooper JD, Johnson DW, Gobe GC (2010) Molecular cell biology of androgen receptor signalling. Int J Biochem Cell Biol 42:813–827

    Article  CAS  PubMed  Google Scholar 

  13. Yonekura S, Terauchi F, Hoshi K, Yamaguchi T, Kawai S (2018) Androgen receptor predicts first and multiple recurrences in non-muscle invasive urothelial carcinoma of the bladder. Pathol Oncol Res. https://doi.org/10.1007/s12253-018-0431-7

    Article  CAS  Google Scholar 

  14. Olsen JR, Azeem W, Hellem MR, Marvyin K, Hua Y, Qu Y, Li L, Lin B, Ke XIS, Øyan AM, Kalland KH (2016) Context dependent regulatory patterns of the androgen receptor and androgen receptor target genes. BMC Cancer 16:377

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Liang L, Li L, Tian J, Lee SO, Dang Q, Huang CK, Yeh S, Erturk E, Bushinsky D, Chang LS, He D, Chang C (2014) Androgen receptor enhances kidney stone-CaOx crystal formation via modulation of oxalate biosynthesis & oxidative stress. Mol Endocrinol 28:1291–1303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Li JY, Zhou T, Gao X, Xu C, Sun Y, Peng Y, Chang Z, Zhang Y, Jiang J, Wang L, Hou J (2010) Testosterone and androgen receptor in human nephrolithiasis. J Urol 184:2360–2363

    Article  CAS  PubMed  Google Scholar 

  17. Chow WH, Dong LM, Devesa SS (2010) Epidemiology and risk factors for kidney cancer. Nat Rev Urol 7:245–257

    Article  PubMed  PubMed Central  Google Scholar 

  18. Bennett NC, Rajandram R, Ng KL, Gobe GC (2014) Evaluation of steroid hormones and their receptors in development and progression of renal cell carcinoma. J Kidney Cancer VHL 1:17–25

    Article  PubMed  PubMed Central  Google Scholar 

  19. Langner C, Ratschek M, Rehak P, Schips L, Zigeuner R (2004) Steroid hormone receptor expression in renal cell carcinoma: an immunohistochemical analysis of 182 tumors. J Urol 171:611–614

    Article  CAS  PubMed  Google Scholar 

  20. Noh SJ, Kang MJ, Kim KM et al (2013) Acetylation status of P53 and the expression of DBC1, SIRT1, and androgen receptor are associated with survival in clear cell renal cell carcinoma patients. Pathology 45:574–580

    Article  CAS  PubMed  Google Scholar 

  21. Huang Q, Sun Y, Ma X, Gao Y, Li X, Niu Y, Zhang X, Chang C (2017) Androgen receptor increases hematogenous metastasis yet decreases lymphatic metastasis of renal cell carcinoma. Nat Commun 8:918

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Foersch S, Schindeldecker M, Keith M, Tagscherer KE, Fernandez A, Stenzel PJ, Pahernik S, Hohenfellner M, Schirmacher P, Roth W, Macher-Goeppinger S (2017) Prognostic relevance of androgen receptor expression in renal cell carcinomas. Oncotarget 8:78545–78555

    Article  PubMed  PubMed Central  Google Scholar 

  23. Vrabel M (2015) Preferred reporting items for systematic reviews and meta-analyses. Oncol Nurs Forum 42:552–554

    Article  PubMed  Google Scholar 

  24. Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25:603–605

    Article  PubMed  Google Scholar 

  25. Ha YS, Lee GT, Modi P, Kwon YS, Ahn H, Kim WJ, Kim IY (2015) Increased expression of androgen receptor mRNA in human renal cell carcinoma cells is associated with poor prognosis in patients with localized renal cell carcinoma. J Urol 194:1441–1448

    Article  CAS  PubMed  Google Scholar 

  26. Williams EM, Higgins JP, Sangoi AR, McKenney JK, Troxell ML (2015) Androgen receptor immunohistochemistry in genitourinary neoplasms. Int Urol Nephrol 4:81–85

    Article  CAS  Google Scholar 

  27. Zhu G, Liang L, Li L, Dang Q, Song W, Yeh S, He D, Chang C (2014) The expression and evaluation of androgen receptor in human renal cell carcinoma. Urology 83:510 e19–5510e24

    Article  Google Scholar 

  28. Nakano E, Tada Y, Fujioka H, Matsuda M, Osafune M, Kotake T, Sato B, Takaha M, Sonoda T (1984) Hormone receptor in renal cell carcinoma and correlation with clinical response to endocrine therapy. J Urol 132:240–245

    Article  CAS  PubMed  Google Scholar 

  29. Klotzl G, Otto U, Becker H, Klosterhalfen H (1987) Determination of androgen, progestin and estrogen receptors with two different assays in renal cell carcinoma. Urol Int 42:100–104

    Article  CAS  PubMed  Google Scholar 

  30. Ronchi E, Pizzocaro G, Miodini P, Piva L, Salvioni R, Di Fronzo G (1984) Steroid hormone receptors in normal and malignant human renal tissue: relationship with progestin therapy. J Steroid Biochem 21:329–335

    Article  CAS  PubMed  Google Scholar 

  31. Concolino G, Marocchi A, Toscano V, Di Silverio F (1981) Nuclear androgen receptor as marker of responsiveness to medroxyprogesterone acetate in human renal cell carcinoma. J Steroid Biochem 15:397–402

    Article  CAS  PubMed  Google Scholar 

  32. Koryakina Y, Ta HQ, Gioeli D (2014) Androgen receptor phosphorylation: biological context and functional consequences. Endocr Relat Cancer 21:T131–T145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lin WJ, Izumi K (2014) Androgen receptor, ccl2, and epithelial-mesenchymal transition: a dangerous affair in the tumor microenvironment. Oncoimmunology 3:e27871

    Article  PubMed  PubMed Central  Google Scholar 

  34. Tonelli F, Alossaimi M, Williamson L, Tate RJ, Watson DG, Chan E, Bittman R, Pyne NJ, Pyne S (2013) The sphingosine kinase inhibitor 2-(p-hyroxyanilino)-4-(p-chlorophenyl) thiazole reduces androgen receptor expression via an oxidative stress- dependent mechanism. Br J Pharmacol 168:1497–1505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Carver BS (2014) Strategies for targeting the androgen receptor axis in prostate cancer. Drug Discov Today 19:1493–1497

    Article  CAS  PubMed  Google Scholar 

  36. Miyamoto H, Yang Z, Chen YT, Ishiguro H, Uemura H, Kubota Y, Nagashima Y, Chang YJ, Hu YC, Tsai MY, Yeh S, Messing EM, Chang C (2007) Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst 99:558–568

    Article  CAS  PubMed  Google Scholar 

  37. Chang C, Lee SO, Yeh S, Chang TM (2014) Androgen receptor (AR) differential roles in hormone-related tumors including prostate, bladder, kidney, lung, breast and liver. Oncogene 33:3225–3234

    Article  CAS  PubMed  Google Scholar 

  38. Schweizer MT, Yu EY (2017) AR-signaling in human malignancies: prostate cancer and beyond. Cancers (Basel) 9:7

    Article  PubMed Central  CAS  Google Scholar 

  39. Vera-Badillo FE, Templeton AJ, de Gouveia P, Diaz-Padilla I, Bedard PL, al-Mubarak M, Seruga B, Tannock IF, Ocana A, Amir E (2014) Androgen receptor expression and outcomes in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst 106:djt319

    Article  PubMed  CAS  Google Scholar 

  40. Grogg A, Trippel M, Pfaltz K, Lädrach C, Droeser RA, Cihoric N, Salhia B, Zweifel M, Tapia C (2015) Androgen receptor status is highly conserved during tumor progression of breast cancer. BMC Cancer 15:872

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Gucalp A, Tolaney S, Isakoff SJ, Ingle JN, Liu MC, Carey LA, Blackwell K, Rugo H, Nabell L, Forero A, Stearns V, Doane AS, Danso M, Moynahan ME, Momen LF, Gonzalez JM, Akhtar A, Giri DD, Patil S, Feigin KN, Hudis CA, Traina TA, on behalf of the Translational Breast Cancer Research Consortium (TBCRC 011) (2013) Phase II trial of bicalutamide in patients with androgen receptor-positive, estrogen receptor-negative metastatic breast Cancer. Clin Cancer Res 19:5505–5512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ma WL, Lai HC, Yeh S, Cai X, Chang C (2014) Androgen receptor roles in hepatocellular carcinoma, fatty liver, cirrhosis and hepatitis. Endocr Relat Cancer 21:R165–R182

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ljungberg B, Bensalah K, Canfield S, Dabestani S, Hofmann F, Hora M, Kuczyk MA, Lam T, Marconi L, Merseburger AS, Mulders P, Powles T, Staehler M, Volpe A, Bex A (2015) EAU guidelines on renal cell carcinoma: 2014 update. Eur Urol 67:913–924

    Article  PubMed  Google Scholar 

  44. Tosco L, Van Poppel H, Frea B, Gregoraci G, Joniau S (2013) Survival and impact of clinical prognostic factors in surgically treated metastatic renal cell carcinoma. Eur Urol 63:646–652

    Article  PubMed  Google Scholar 

  45. Kim SH, Kim S, Joo J, Seo HK, Joung JY, Lee KH, Chung J (2016) A retrospective study of predictive factors for unexpectedly prolonged or shortened progression-free survival and overall survival among patients with metastatic renal cell carcinoma who received first-line targeted therapy. BMC Cancer 16:577

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Wang K, Sun Y, Tao W, Fei X, Chang C (2017) Androgen receptor (AR) promotes clear cell renal cell carcinoma (ccRCC) migration and invasion via altering the circHIAT1/miR-195-5p/29a-3p/29c-3p/CDC42 signals. Cancer Lett 394:1–12

    Article  CAS  PubMed  Google Scholar 

  47. Zhai W, Sun Y, Guo C, Hu G, Wang M, Zheng J, Lin WY, Huang Q, Li G, Zheng J, Chang C (2017) LncRNA-SARCC suppresses renal cell carcinoma (RCC) progression via altering the androgen receptor (AR)/miRNA-143-3p signals. Cell Death Differ 24:1502–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Czarnecka AM, Niedzwiedzka M, Porta C, Szczylik C (2016) Hormone signaling pathways as treatment targets in renal cell cancer (review). Int J Oncol 48:2221–2235

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, Tongji Hospital, Tongji Medical School, Huazhong University of Science and Technology, No.1095 Jie Fang Avenue, Hankou, Wuhan, 430030, People’s Republic of China

    Peng Yuan, Yue Ge, Xiao Liu, Shen Wang, Zhangqun Ye, Hua Xu & Zhiqiang Chen

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  1. Peng Yuan
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  2. Yue Ge
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  3. Xiao Liu
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  4. Shen Wang
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  6. Hua Xu
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Contributions

study concepts and design: P Yuan, ZQ Ye, H Xu, ZQ Chen; literature research: P Yuan, Y Ge, S Wang; study selection, data extraction and quality assessment: P Yuan, Y Ge, X Liu, ZQ Chen; statistical analysis: P Yuan, Y Ge, X Liu; manuscript preparation: P Yuan, Y Ge, ZQ Chen; manuscript editing: P Yuan, S Wang, ZQ Chen; manuscript review: ZQ Ye, H Xu, ZQ Chen; All authors approved the final version to be published.

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Correspondence to Zhiqiang Chen.

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Yuan, P., Ge, Y., Liu, X. et al. The Association of Androgen Receptor Expression with Renal Cell Carcinoma Risk: a Systematic Review and Meta-Analysis. Pathol. Oncol. Res. 26, 605–614 (2020). https://doi.org/10.1007/s12253-019-00650-z

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