DEF6 expression in ovarian carcinoma correlates with poor patient survival

Abstract

BackgroundIncreased expression of DEF6 is correlated with the malignant behavior of various cancers. Both DEF6 and p16 contribute to the regulation of cell cycle progression, and p53 plays important role in the cell cycle checkpoints. This study was designed to elucidate the prognostic significance of DEF6, p53 and p16 immunoexpressions in different histology subtypes of ovarian carcinoma.MethodsImmunohistochemistry results of DEF6, p53 and p16 on ovarian carcinoma were compared with histology subtypes, clinical data, overall survival (OS) and disease-free survival (DFS) by Cox regression and Kaplan-Meier analysis.ResultsWe studied 180 cases of ovarian carcinomas (75 high-grade serous, 41 clear cell, 36 mucinous and 28 endometrioid), including 109 FIGO stage I-II cases and 71 FIGO stage III-IV cases. Ovarian carcinomas positive for both DEF6 and p16 expression were associated with the worst OS (P = 0.027) and DFS (P = 0.023), whereas those negative for both DEF6 and p16 had the best OS and DFS. Aberrant p53 expression combined with positive DEF6 was associated with worst OS (P = 0.031) and DFS (P = 0.028). Kaplan-Meier analysis showed that significantly shorter survival rates were seen in patients with high expressions of DEF6 (P = 0.008) and p16 (P = 0.022). Patients with aberrant p53 expression in high-grade serous carcinoma (P = 0.012) and patients with high DEF6 expression in clear cell carcinoma (P = 0.001) were also associated with shorter overall survival. In univariate analysis, FIGO stage, DEF6 and p16 were associated with poor prognosis. DEF6 expression was the only independent prognostic factor correlated with shorted OS (HR 2.115; P = 0.025) and DFS (HR 2.248; P = 0.016) upon multivariate analysis.ConclusionsDEF6 expression may serve as an independent prognostic factor, and interacted positively with p16 toward high tumor stage and shorter survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s13000-016-0518-y) contains supplementary material, which is available to authorized users.

Distinct methylation profile of mucinous ovarian carcinoma reveals susceptibility to proteasome inhibitors

“…From the years 1999 to 2013, totally 94 patients including 27 mucinous ovarian adenomas, 38 MuOCs and 29 SeOCs were retrieved from the archival pathology files of the Taipei Medical University 35 and Taipei Medical University Joint Biobank. The hematoxylin and eosin-stained slides were reviewed by two pathologists, and representative blocks with whole tissue sections of ovarian tumors were selected for immunohistochemistry (Supporting Information, Table S4).…”

Increased DEF6 expression is correlated with metastasis and poor prognosis in human osteosarcoma

“…However, a robust biomarker for predicting metastasis and prognosis in patients with OS does not exist (37). Accumulating evidence suggests that in various types of cancer, such as ovarian carcinoma and colorectal cancer, DEF6 is associated with disease progression and poor prognosis (12,(17)(18)(19)(20). In the present study, the results demonstrated that DEF6 was widely expressed in human OS tissues and that its accumulation was positively correlated with advanced Enneking stage and distant metastases.…”

“…DEF6, also known as IBP, is a pivotal driver responsible for regulating immune cell biology and autoimmunity, and has been frequently been reported to be amplified in several types of cancer (8,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The results of the current study determined whether DEF6 is a novel oncogene in OS.…”

“…Although numerous studies have focused on the role of DEF6 in the immune system, abnormal DEF6 expression levels in non-immune cells, particularly tumor cells, indicate a potential function of DEF6 in tumorigenesis regulation (12,17,18). DEF6 has been reported to be highly expressed in breast carcinoma, ovarian cancer, colorectal cancer, oral squamous cell carcinoma and extraskeletal myxoid chondrosarcoma (17)(18)(19)(20)(21), exhibiting various malignant behaviors and cancer cell biology, including proliferation (19), autophagy (22), invasion (20) and epithelial-mesenchymal transition (12). Additionally, Rho-GTPase and mammalian target of rapamycin (mTOR) signaling pathways, which serve a key role in OS tumorigenesis and metastasis (3,8), are targets of DEF6 that facilitate tumor cell metastasis and enhance tumorigenic potential (12,22).…”

“…Previous studies have reported an abnormal expression of DEF6 in multiple malignant tumors, indicating that DEF6 functions as an oncogene (17)(18)(19)(20)(21). IHC staining was performed to examine the expression of DEF6 in 58 human OS tissues and to determine the role of DEF6 in OS development.…”