Yes-Associated Protein Expression Is Correlated to the Differentiation of Prostate Adenocarcinoma
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background: Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods: The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results: YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions: The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.
Abstract
Background: Yes-associated protein (YAP) in the Hippo signaling pathway is a growth control pathway that regulates cell proliferation and stem cell functions. Abnormal regulation of YAP was reported in human cancers including liver, lung, breast, skin, colon, and ovarian cancer. However, the function of YAP is not known in prostate adenocarcinoma. The purpose of this study was to investigate the role of YAP in tumorigenesis, differentiation, and prognosis of prostate adenocarcinoma. Methods: The nuclear and cytoplasmic expression of YAP was examined in 188 cases of prostate adenocarcinoma using immunohistochemistry. YAP expression levels were evaluated in the nucleus and cytoplasm of the prostate adenocarcinoma and the adjacent normal prostate tissue. The presence of immunopositive tumor cells was evaluated and interpreted in comparison with the patients’ clinicopathologic data. Results: YAP expression levels were not significantly different between normal epithelial cells and prostate adenocarcinoma. However, YAP expression level was significantly higher in carcinomas with a high Gleason grades (8–10) than in carcinomas with a low Gleason grades (6–7) (p < .01). There was no statistical correlation between YAP expression and stage, age, prostate-specific antigen level, and tumor volume. Biochemical recurrence (BCR)–free survival was significantly lower in patients with high YAP expressing cancers (p = .02). However high YAP expression was not an independent prognostic factor for BCR in the Cox proportional hazards model. Conclusions: The results suggested that YAP is not associated with prostate adenocarcinoma development, but it may be associated with the differentiation of the adenocarcinoma. YAP was not associated with BCR.
참고문헌 (35)
- Diallo JS, "Co-assessment of cytoplasmic and nuclear androgen receptor location in prostate specimens : potential implications for prostate cancer development and prognosis", BJU Int, 101, pp.1302~1309 (2008)
- 정재영, "Current Trends in the Incidence and Survival Rate of Urological Cancers in Korea", Cancer Research and Treatment, 49(3), pp.607~615 (2017), 대한암학회
- Zhang L, "The hippo pathway effector YAP regulates motility, invasion, and castration-resistant growth of prostate cancer cells", Mol Cell Biol, 35, pp.1350~1362 (2015)
- Epstein JI, "The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma", Am J Surg Pathol, 29, pp.1228~1242 (2005)
- McMenamin ME, "Loss of PTEN expression in paraffin-embedded primary prostate cancer correlates with high Gleason score and advanced stage", Cancer Res, 59, pp.4291~4296 (1999)
- Edgar BA, "From cell structure to transcription : Hippo forges a new path", Cell, 124, pp.267~273 (2006)
- Lai ZC, "Control of cell proliferation and apoptosis by mob as tumor suppressor, mats", Cell, 120, pp.675~685 (2005)
- SteinhardtAA, "Expression of Yes-associated protein in common solid tumors", Hum Pathol, 39, pp.1582~1589 (2008)
- Wang Y, "Overexpression of yes-associated protein contributes to progression and poor prognosis of non-small-cell lung cancer", Cancer Sci, 101, pp.1279~1285 (2010)
- Cordenonsi M, "The Hippo transducer TAZ confers cancer stem cell-related traits on breast cancer cells", Cell, 147, pp.759~772 (2011)
- DiAgostino S, "YAP enhances the proproliferative transcriptional activity of mutant p53 proteins", EMBO Rep, 17, pp.188~201 (2016)
- Lee KW, "Significant association of oncogene YAP1 with poor prognosis and cetuximab resistance in colorectal cancer patients", Clin Cancer Res, 21, pp.357~364 (2015)
- Kim GJ, "Increased expression of Yes-associated protein 1 in hepatocellular carcinoma with stemness and combined hepatocellular-cholangiocarcinoma", PLoS One, 8, pp.e75449~ (2013)
- Morvaridi S, "Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis", Sci Rep, 5, pp.16759~ (2015)
- Johnson R, "The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment", Nat Rev Drug Discov, 13, pp.63~79 (2014)
- Grasso CS, "The mutational landscape of lethal castration-resistant prostate cancer", Nature, 487, pp.239~243 (2012)
- Hu X, "Loss ofYAP protein in prostate cancer is associated with Gleason score increase", Tumori, 101, pp.189~193 (2015)
- Varambally S, "Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression", Cancer Cell, 8, pp.393~406 (2005)
- Chandran UR, "Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process", BMC Cancer, 7, pp.64~ (2007)
- Yu YP, "Gene expression alterations in prostate cancer predicting tumor aggression and preceding development of malignancy", J Clin Oncol, 22, pp.2790~2799 (2004)
- Satake H, "The ubiquitin-like molecule interferon-stimulated gene 15 is overexpressed in human prostate cancer", Oncol Rep, 23, pp.11~16 (2010)
- Planche A, "Identification of prognostic molecularfeatures in the reactive stroma of human breast and prostate cancer", PLoS One, 6, pp.e18640~ (2011)
- Arredouani MS, "Identification of the transcription factor single-minded homologue 2 as a potential biomarker and immunotherapy target in prostate cancer", Clin Cancer Res, 15, pp.5794~5802 (2009)
- Nanni S, "Epithelial-restricted gene profile of primary cultures from human prostate tumors: a molecular approach to predict clinical behavior of prostate cancer", Mol Cancer Res, 4, pp.79~92 (2006)
- Rosenbluh J, "beta-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis", Cell, 151, pp.1457~1473 (2012)
- Dong J, "Elucidation of a universal sizecontrol mechanism in Drosophila and mammals", Cell, 130, pp.1120~1133 (2007)
- Shen S, "AmiR-130a-YAP positive feedback loop promotes organ size and tumorigenesis", Cell Res, 25, pp.997~1012 (2015)
- Xiao W, "Mutual interaction between YAP and c-Myc is critical for carcinogenesis in liver cancer", Biochem Biophys Res Commun, 439, pp.167~172 (2013)
- Zhang W, "Downstream of mutant KRAS, the transcription regulator YAP is essential for neoplastic progression to pancreatic ductal adenocarcinoma", Sci Signal, 7, pp.ra42~ (2014)
- Zanconato F, "YAP", TAZ at the roots of cancer, 2016, pp.29, 783~803
- Guo Y, "Functional and clinical evidence that TAZ is a candidate oncogene in hepatocellular carcinoma", J Cell Biochem, 116, pp.2465~2475 (2015)
- Bartucci M, "TAZ is required for metastatic activity and chemoresistance of breast cancer stem cells", Oncogene, 34, pp.681~690 (2015)
- Han KR, "Prostate stem cell antigen expression is associated with gleason score, seminal vesicle invasion and capsularinvasion in prostate cancer", J Urol, 171, pp.1117~1121 (2004)
- Kim DH, "Differential expression of Yes-associated protein and phosphorylated Yes-associated protein is correlated with expression of Ki-67 and phospho-ERK in colorectal adenocarcinoma", Histol Histopathol, 28, pp.1483~1490 (2013)
- Hu X, "Overexpression of YAP1 is correlated with progression, metastasis and poor prognosis in patients with gastric carcinoma", Pathol Oncol Res, 20, pp.805~811 (2014)
