ABSTRACT
OBJECTIVE: To investigate FOXO1 expression in epithelial ovarian cancer (EOC), and to explore its correlation with clinicopathological parameters and prognosis of EOC. METHODS: Two hundred and sixteen cases of paraffin-embedded EOC and 41 paratumor tissues from 2009 to 2017 that had been pathologically confirmed at the memorial hospital of Sun Yat-sen University were included in this study, and the expression of FOXO1 was performed by immunohistochemistry using a polyclonal antibody specific for FOXO1. RESULTS: FOXO1 protein expression is associated with Recurrence free and overall survival in EOC patients; In addition, FOXO1 expression is associated with age, FIGO stage, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence and differentiation grade; Moreover, in a multivariate model FOXO1 overexpression was an independent predictor of poor survival in EOC. CONCLUSION: FOXO1 may play a candidate oncogenic role in EOC, and FOXO1 is a useful independent prognostic marker in EOC, and it may provide a candidate target therapy in future.
Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Ovarian Epithelial/genetics , Forkhead Box Protein O1/metabolism , Carcinoma, Ovarian Epithelial/mortality , Disease-Free Survival , Female , Humans , Middle Aged , PrognosisABSTRACT
OBJECTIVE: LGR4 expression in serous ovarian cancer paraffin-embedded tissues and fresh tissues were investigated, and its expression associated with clinicopathological parameters and prognosis in serous ovarian cancer was explored. METHODS: From Dec, 2009 to Jan, 2020, 122 paraffin-embedded serous ovarian cancer patients and 41 paired paratumor tissues who were both diagnosed and operated at the memorial hospital of Sun Yat-sen University and Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were selected in this research, respectively, and all of these tissues were performed by immunohistochemistry (IHC) with a polyclonal antibody for LGR4. Meanwhile, from Aug, 2013 to Mar, 2019, 15 cases of serous ovarian cancer fresh tissues and 15 cases of paratumor fresh tissues who were operated at Integrated Hospital of Traditional Chinese Medicine, Southern Medical University were performed with Quantitative Real-time PCR to detect the mRNA expression of LGR4, respectively. RESULTS: LGR4 expression was much higher both in paraffin-embedded and fresh cancer tissues than that in paratumor tissues, respectively, and its expression was associated with recurrence free survival and overall survival in serous ovarian cancer patients. Moreover, in a multivariate model LGR4 was an indeed independent predictor of poor survival in serous ovarian cancer patients. CONCLUSION: LGR4 is upregulated in serous ovarian cancer, and LGR4 is an indeed useful independent prognostic predictor in serous ovarian cancer, and it may provide important clinical value of serous ovarian cancer.
Subject(s)
Carcinoma, Ovarian Epithelial/metabolism , Cystadenocarcinoma, Serous/metabolism , Ovarian Neoplasms/metabolism , Receptors, G-Protein-Coupled/biosynthesis , Biomarkers, Tumor/biosynthesis , Biomarkers, Tumor/metabolism , Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/pathology , Cystadenocarcinoma, Serous/genetics , Cystadenocarcinoma, Serous/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Middle Aged , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Paraffin Embedding , Prognosis , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , Survival Analysis , Up-RegulationABSTRACT
The pathogenesis of ovarian cancer remains to be elucidated. Our previous study demonstrated that myosin heavy chain 9 (MYH9) overexpression was associated with poor prognosis of epithelial ovarian cancer. However, the mechanism of MYH9 and its regulation by microRNA (miR) is not clear. The results of the present study demonstrated that miR-6089 was one of the microRNAs targeting MYH9, and miR-6089 overexpression suppressed ovarian cancer cell proliferation, migration, invasion and metastasis in vivo and in vitro. Mechanistic studies confirmed that miR-6089 directly targeted MYH9 to inactivate the Wnt/ß-catenin signalling pathway and its downstream epithelial-to-mesenchymal transition (EMT), cell-cycle factors and c-Jun, whereas overexpression of MYH9 reversed the inhibitory effects of miR-6089 overexpression in ovarian cancer cells by upregulating the Wnt/ß-catenin and its downstream EMT, cell-cycle factors and c-Jun. Interestingly, miR-6089 was transcriptionally inhibited by c-Jun, a transcription factor which could be induced by MYH9 via the Wnt/ß-catenin pathway. Thus miR-6089/MYH9/ß-catenin/c-Jun formed a negative feedback loop in ovarian cancer. In clinical samples, miR-6089 negatively correlated with MYH9 expression. Our study is the first to demonstrate that miR-6089 serves as a tumor-suppressive miRNA, and miR-6089/MYH9/ß-catenin/c-Jun negative feedback loop inhibits ovarian cancer carcinogenesis and progression.
Subject(s)
Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic , Genes, jun , MicroRNAs/genetics , Myosin Heavy Chains/genetics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , beta Catenin/genetics , Animals , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Cell Transformation, Neoplastic/metabolism , Disease Models, Animal , Disease Progression , Disease Susceptibility , Female , Genes, Reporter , Humans , Mice , Myosin Heavy Chains/metabolism , Ovarian Neoplasms/metabolism , RNA Interference , Wnt Signaling Pathway , beta Catenin/metabolismABSTRACT
The aim of the present study was to investigate the expression of myosin 9 (MYH9) in epithelial ovarian cancer and to explore its correlation with the clinicopathological parameters and prognosis of epithelial ovarian cancer (EOC). A total of 265 cases of paraffin-embedded ovarian cancer tissues and 41 paratumor tissues which had been pathologically confirmed at the Memorial Hospital of Sun Yat-sen University from 2009 to 2017 were included in the present study. MYH9 expression was investigated with immunohistochemistry using a polyclonal antibody specific for MYH9. MYH9 expression is associated with disease progression free and overall survival in epithelial ovarian cancer patients; and the expression of MYH9 is associated with International Federation of Gynecology and Obstetrics stage, lymph node metastasis, intraperitoneal metastasis, survival status (at last follow-up), intraperitoneal recurrence, residual tumor size and ascites with tumor cells. Moreover, in a multivariate model MYH9 overexpression was an independent predictor of poor survival in epithelial ovarian cancer. MYH9 may be a candidate that plays a oncogenic role in epithelial ovarian cancer. MYH9 is a useful independent prognostic marker in epithelial ovarian cancer, and it may provide a candidate target therapy treatment of ovarian cancer in the future.
ABSTRACT
OBJECTIVES: To investigate TCF4 expression in epithelial ovarian cancer, and to explore its correlation with clinicopathological parameters and clinical prognosis of epithelial ovarian cancer. METHODS: From 2009 to 2017, 188 cases of paraffin-embedded epithelial ovarian cancer tissues and 41 paratumor ovarian tissues which had been confirmed at the memorial hospital of Sun Yat-sen University were collected in this study, and the expression of TCF4 was performed by immunohistochemistry using a polyclonal antibody specific for TCF4. RESULTS: The expression of TCF4 protein was associated with disease progression free survival and overall survival in epithelial ovarian cancer patients; and TCF4 overexpression was associated with age, FIGO stage, lymph node metastasis, intraperitoneal metastasis, intestinal metastasis, vital status, intraperitoneal recurrence, and serum CA153. Moreover, in a multivariate Cox regression analysis TCF4 overexpression was an indeed independent prognostic factor in epithelial ovarian cancer. CONCLUSIONS: TCF4 may play an oncogenic role in epithelial ovarian cancer, and TCF4 is a useful independent prognostic biomarker of epithelial ovarian cancer, and it may provide a candidate target therapy treatment in future.
Subject(s)
Carcinoma, Ovarian Epithelial/genetics , Carcinoma, Ovarian Epithelial/pathology , Gene Expression Regulation, Neoplastic , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Transcription Factor 7-Like 2 Protein/genetics , Transcription Factor 7-Like 2 Protein/metabolism , Antigens, Neoplasm/blood , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Ovarian Epithelial/metabolism , Female , Humans , Immunohistochemistry , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neoplasm Staging , Ovarian Neoplasms/metabolism , Prognosis , Survival AnalysisABSTRACT
Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor suppressor gene identified from the human bladder carcinoma. Our previous studies have shown that BLCAP overexpression could inhibit cell growth by inducing apoptosis in HeLa cells [Zuo Z, Zhao M, Liu J, Gao G, Wu X: Tumor Biol 27: 221-226, 2006]. Such evidence suggests the alterations in BLCAP may play an important role in tumorigenesis. To further study the biological function of the BLCAP gene, we constructed a recombinant retroviral vector encoding BLCAP cDNA. Overexpressed BLCAP, via stable infection of exogenous BLCAP, resulted in growth inhibition of the human tongue cancer cell line Tca8113 in vitro, accompanied by S phase cell cycle arrest and apoptosis. The growth inhibition was correlated with up-regulation of p21(WAF1/CIP1 )expression and down-regulation of Bcl-XL and Bcl-2 expressions. However, p53 expression and NF-kappaB activity remained unchanged post infection. Furthermore, no changes in p53 phosphorylation at Ser46 and nuclear localization, which are critical to p53 function, were observed in BLCAP-overexpressed cells. Taken together, BLCAP may play a role not only in regulating cell proliferation but also in coordinating apoptosis and cell cycle via a novel way independent of p53 and NF-kappaB.
