Article Data

  • Views 922
  • Dowloads 113

Original Research

Open Access

The effects of protocadherin 8 and WWOX in prostate adenocarcinoma

  • Mürüvvet Akçay Çelik1,*,
  • Havva Erdem1
  • Soner Çankaya2
  • Yeliz Kaşko Arıcı3

1Department of Pathology, Faculty of Medicine, University of Ordu, 52200 Ordu, Turkey

2Department of Sports Management, Faculty of Yaşar Doğu Sport Sciences, University of Ondokuz Mayis, 55200 Samsun, Turkey

3Department of Biostatistics and Medical Informatics, Faculty of Medicine, University of Ordu, 52200 Ordu, Turkey

DOI: 10.31083/j.jomh1804102 Vol.18,Issue 4,April 2022 pp.1-6

Submitted: 29 September 2021 Accepted: 15 November 2021

Published: 30 April 2022

*Corresponding Author(s): Mürüvvet Akçay Çelik E-mail: drmakcaycelik@gmail.com

Abstract

Objective: The protocadherin 8 (PCDH8) gene, located on chromosome 13q14.3 encodes an integral membrane protein. WWOX (frag-ile site FRA16D oxido-reductase) is a tumor suppressor gene located in region 16q23.324.1. The aim of this study was to investigate the staining pattern of protocadherin 8 and WWOX in adenomatous hyperplasia and prostate adenocarcinoma. Methods: Seventy adenoma-tous hyperplasia and 70 prostate adenocarcinoma preparations stored at the pathology department from 2013–2016 were retrospectively analyzed. Samples immunohistochemically stained with WWOX or protocadherin 8 were evaluated by two pathologists under a light microscope. After pathological investigation of the samples, the expression of WWOX and protocadherin 8 was scored. WWOX and PCDH8 expression was assessed semi-quantitatively according to staining intensity scored as none, mild, moderate, and strong (0 to 3+). For analysis of the data, the mild, moderate and strong staining scores were combined (as positive) and the data were classified as negative or positive. Differences in the WWOX or protocadherin 8 staining results between adenomatous hyperplasia and prostate adenocarci-noma cases were examined using a two-way chi-square test and binary logistic regression analysis. Result: Statistical analysis showed that WWOX expression was higher in adenomatous hyperplasia than in prostate adenocarcinomas. This difference was statistically sig-nificant (p = 0.035). There was no difference in PCDH8 expression between adenomatous hyperplasia and prostate adenocarcinoma samples (p = 0.217). Conclusion: In this study, the expression of WWOX decreased and the expression of PCDH8 remained unchanged in PCa cases. In terms of prognostic significance, it can be concluded that WWOX is a good prognostic parameter, while PCDH8 was an ineffective prognostic marker. In addition, the investigation of protocadherin 8 in larger series may provide more meaningful results.

Keywords

protocadherin 8; WWOX; prostate; logistic regression analysis

Cite and Share

Mürüvvet Akçay Çelik,Havva Erdem,Soner Çankaya,Yeliz Kaşko Arıcı. The effects of protocadherin 8 and WWOX in prostate adenocarcinoma. Journal of Men's Health. 2022. 18(4);1-6.

References

[1] Abate-Shen C, Shen MM. Molecular genetics of prostate cancer. Genes & Development. 2000; 14: 2410–2434.

[2] Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. The Journal of Urology. 1984; 132: 474–479.

[3] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of in-cidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394–424.

[4] Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bet-tio M, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Euro-pean Journal of Cancer. 2018; 103: 356–387.

[5] Lin Y, Ma J, Luo X, Guan T, Li Z. Clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer. The Journal of International Medical Research. 2013; 41: 48–54.

[6] Lin Y, Wang Y, Ma J, Li W. Clinical significance of protocad-herin 8 (PCDH8) promoter methylation in non-muscle invasive bladder cancer. Journal of Experimental and Clinical Cancer Re-search. 2014; 33: 68.

[7] Kim S, Yasuda S, Tanaka H, Yamagata K, Kim H. Non-clustered protocadherin. Cell Adhesion & Migration. 2011; 5: 97–105.

[8] Chen T, Long B, Ren G, Xiang T, Li L, Wang Z, et al. Proto-cadherin20 Acts as a Tumor Suppressor Gene: Epigenetic Inac-tivation in Nasopharyngeal Carcinoma. Journal of Cellular Bio-chemistry. 2015; 116: 1766–1775.

[9] Imoto I, Izumi H, Yokoi S, Hosoda H, Shibata T, Hosoda F, et al. Frequent silencing of the candidate tumor suppressor PCDH20 by epigenetic mechanism in non-small-cell lung cancers. Cancer Research. 2006; 66: 4617–4626.

[10] Strehl S, Glatt K, Liu QM, Glatt H, Lalande M. Characterization of two novel protocadherins (PCDH8 and PCDH9) localized on human chromosome 13 and mouse chromosome 14. Genomics. 1998; 53: 81–89.

[11] Yu JS, Koujak S, Nagase S, Li C, Su T, Wang X, et al. PCDH8, the human homolog of PAPC, is a candidate tumor suppressor of breast cancer. Oncogene. 2008; 27: 4657–4665.

[12] Niu W, Gui S, Lin Y, Fu X, Ma J, Li W. Promoter methylation of protocadherin8 is an independent prognostic factor for biochem-ical recurrence of early-stage prostate cancer. Medical Science Monitor. 2014; 20: 2584–2589.

[13] Nunez MI, Ludes-Meyers J, Aldaz CM. WWOX protein expres-sion in normal human tissues. Journal of Molecular Histology. 2006; 37: 115–125.

[14] Baryła I, Styczeń-Binkowska E, Bednarek AK. Alteration of WWOX in human cancer: a clinical view. Experimental Biol-ogy and Medicine. 2015; 240: 305–314.

[15] Hezova R, Ehrmann J, Kolar Z. WWOX, a new potential tumor suppressor gene. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2007; 151: 11–15.

[16] Aqeilan RI, Croce CM. WWOX in biological control and tu-morigenesis. Journal of Cellular Physiology. 2007; 212: 307–310.

[17] Chang N, Hsu L, Lin Y, Lai F, Sheu H. WW domain-containing oxidoreductase: a candidate tumor suppressor. Trends in Molec-ular Medicine. 2007; 13: 12–22.

[18] Watanabe A, Hippo Y, Taniguchi H, Iwanari H, Yashiro M, Hi-rakawa K, et al. An opposing view on WWOX protein function as a tumor suppressor. Cancer Research. 2003; 63: 8629–8633.

[19] Qin HR, Iliopoulos D, Nakamura T, Costinean S, Volinia S, Druck T, et al. Wwox suppresses prostate cancer cell growth through modulation of ErbB2-mediated androgen receptor sig-naling. Molecular Cancer Research. 2007; 5: 957–965.

[20] Izycka N, Sterzynska K, Januchowski R, Nowak-Markwitz E. Semaphorin 3A (SEMA3A), protocadherin 9 (PCDH9), and S100 calcium binding protein A3 (S100A3) as potential biomarkers of carcinogenesis and chemoresistance of differ-ent neoplasms, including ovarian cancer- review of literature. Ginekologia Polska. 2019; 90: 223–227.

[21] He Y, WangZ, Liu C, Gong Z, Li Y, Lu T, et al. Protocadherin 17 is a tumor suppressor and is frequently methylated in nasopha-ryngeal carcinoma. Cancer Management and Research. 2019; 11: 1601–1613.

[22] Tang X, Yin X, Xiang T, Li H, Li F, Chen L, et al. Protocad-herin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer. Cancer Biomarkers. 2013; 12: 11–19.

[23] Li Z, Chim JCS, Yang M, Ye J, Wong BCY, Qiao L. Role of PCDH10 and its hypermethylation in human gastric cancer. Biochimica Et Biophysica Acta. 2012; 1823: 298–305.

[24] Zhong X, Shen H, Mao J, Zhang J, Han W. Epigenetic silenc-ing of protocadherin 10 in colorectal cancer. Oncology Letters. 2017; 13: 2449–2453.

[25] Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao SW, et al. Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene. 2006; 25: 1070–1080.

[26] Zhao Y, Yang Y, Trovik J, Sun K, Zhou L, Jiang P, et al. A novel wnt regulatory axis in endometrioid endometrial cancer. Cancer Research. 2014; 74: 5103–5117.

[27] Lin YL, Li ZG, He ZK, Guan TY, Ma JG. Clinical and prognos-tic significance of protocadherin-10 (PCDH10) promoter methy-lation in bladder cancer. The Journal of International Medical Research. 2012; 40: 2117–2123.

[28] Yu J, Cheng YY, Tao Q, Cheung KF, Lam CNY, Geng H, et al. Methylation of protocadherin 10, a novel tumor suppressor, is associated with poor prognosis in patients with gastric cancer. Gastroenterology. 2009; 136: 640–651.e1.

[29] He D, Zeng Q, Ren G, Xiang T, Qian Y, Hu Q, et al. Protocad-herin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma. European Journal of Cancer Prevention. 2012; 21: 569–575.

[30] Zhang D, Zhao W, Liao X, Bi T, Li H, Che X. Frequent silencing of protocadherin 8 by promoter methylation, a candidate tumor suppressor for human gastric cancer. Oncology Reports. 2012; 28: 1785–1791.

[31] Li Y, Liu C, Wang Z, Hu G. Expression of protocadherin8: Function as a tumor suppressor in hypopharyngeal carcinoma. Cancer Biomarkers. 2018; 22: 495–502.

[32] Park JY. Promoter hypermethylation in prostate cancer. Cancer Control. 2010; 17: 245–255.

[33] Zhang P, Wang H, Wang J, Liu Q, Wang Y, Feng F, et al. As-sociation between protocadherin 8 promoter hypermethylation and the pathological status of prostate cancer. Oncology Letters. 2017; 14: 1657–1664.

[34] Nunez MI, Ludes-Meyers J, Abba MC, Kil H, Abbey NW, Page RE, et al. Frequent loss of WWOX expression in breast can-cer: correlation with estrogen receptor status. Breast Cancer Re-search and Treatment. 2005; 89: 99–105.

[35] Gourley C, Paige AJW, Taylor KJ, Ward C, Kuske B, Zhang J, et al. WWOX gene expression abolishes ovarian cancer tu-morigenicity in vivo and decreases attachment to fibronectin via integrin alpha3. Cancer Research. 2009; 69: 4835–4842.

[36] Aqeilan RI, Kuroki T, Pekarsky Y, Albagha O, Trapasso F, Baffa R, et al. Loss of WWOX expression in gastric carcinoma. Clin-ical Cancer Research. 2004; 10: 3053–3058.

[37] Li Y, Wu C, Chen W, Huang Y, Chai C. The expression and sig-nificance of WWOX and β-catenin in hepatocellular carcinoma. Acta Pathologica Microbiologica Et Immunologica Scandinav-ica. 2013; 121: 120–126.

[38] Pospiech K, Płuciennik E, Bednarek AK. WWOX Tumor Sup-pressor Gene in Breast Cancer, a Historical Perspective and Fu-ture Directions. Frontiers in Oncology. 2018; 8: 345.

[39] Yang L, Liu B, Huang B, Deng J, Li H, Yu B, et al. A functional copy number variation in the WWOX gene is associated with lung cancer risk in Chinese. Human Molecular Genetics. 2013; 22: 1886–1894.

[40] Yu K, Fan J, Ding X, Li C, Wang J, Xiang Y, et al. Associa-tion study of a functional copy number variation in the WWOX gene with risk of gliomas among Chinese people. International Journal of Cancer. 2014; 135: 1687–1691.

[41] Lo J, Chou Y, Lai F, Hsu L. Regulation of cell signaling and apoptosis by tumor suppressor WWOX. Experimental Biology and Medicine. 2015; 240: 383–391.

[42] Hughes C, Murphy A, Martin C, Sheils O, O’Leary J. Molecu-lar pathology of prostate cancer. Journal of Clinical Pathology. 2005; 58: 673–684.

[43] Wen J, Xu Z, Li J, Zhang Y, Fan W, Wang Y, et al. De-creased WWOX expression promotes angiogenesis in osteosar-coma. Oncotarget. 2017; 8: 60917–60932.

[44] Kurek KC, Del Mare S, Salah Z, Abdeen S, Sadiq H, Lee S, et al. Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression. Cancer Research. 2010; 70: 5577–5586.

[45] Fabbri M, Iliopoulos D, Trapasso F, Aqeilan RI, Cimmino A, Zanesi N, et al. WWOX gene restoration prevents lung can-cer growth in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2005; 102: 15611–15616.

[46] Nakayama S, Semba S, Maeda N, Matsushita M, Kuroda Y, Yokozaki H. Hypermethylation-mediated reduction of WWOX expression in intraductal papillary mucinous neoplasms of the pancreas. British Journal of Cancer. 2009; 100: 1438–1443.

[47] Pimenta FJ, Cordeiro GT, Pimenta LGGS, Viana MB, Lopes J, Gomez MV, et al. Molecular alterations in the tumor suppressor gene WWOX in oral leukoplakias. Oral Oncology. 2008; 44: 753–758.

[48] Hong Q, Sze C, Lin S, Lee M, He R, Schultz L, et al. Comple-ment C1q activates tumor suppressor WWOX to induce apopto-sis in prostate cancer cells. PLoS ONE. 2009; 4: e5755.

[49] Hong Q, Hsu LJ, Schultz L, Pratt N, Mattison J, Chang NS. Zfra affects TNF-mediated cell death by interacting with death do-main protein TRADD and negatively regulates the activation of NF-kappaB, JNK1, p53 and WOX1 during stress response. BMC Molecular and Cell Biology. 2007; 8: 50.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,200 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Directory of Open Access Journals (DOAJ) DOAJ is a unique and extensive index of diverse open access journals from around the world, driven by a growing community, committed to ensuring quality content is freely available online for everyone.

SCImago The SCImago Journal & Country Rank is a publicly available portal that includes the journals and country scientific indicators developed from the information contained in the Scopus® database (Elsevier B.V.)

Publication Forum - JUFO (Federation of Finnish Learned Societies) Publication Forum is a classification of publication channels created by the Finnish scientific community to support the quality assessment of academic research.

Scopus: CiteScore 0.9 (2023) Scopus is Elsevier's abstract and citation database launched in 2004. Scopus covers nearly 36,377 titles (22,794 active titles and 13,583 Inactive titles) from approximately 11,678 publishers, of which 34,346 are peer-reviewed journals in top-level subject fields: life sciences, social sciences, physical sciences and health sciences.

Norwegian Register for Scientific Journals, Series and Publishers Search for publication channels (journals, series and publishers) in the Norwegian Register for Scientific Journals, Series and Publishers to see if they are considered as scientific. (https://kanalregister.hkdir.no/publiseringskanaler/Forside).

Submission Turnaround Time

Conferences

Top