The EMT (epithelial-mesenchymal-transition)-related protein expression indicates the metastatic status and prognosis in patients with ovarian cancer

Abstract

ObjectivesThe epithelial-mesenchymal-transition (EMT) is an important step in the invasion and metastasis of cancer. A critical molecular feature of this process is the downregulation of the E-cadherin expression, which is primarily controlled by Snail-related zinc-finger transcription factors. The aim of this study was to evaluate the prognostic impact of the expression of EMT-related proteins (E-cadherin and Snail) in patients with ovarian cancer.MethodsAn immunohistochemical analysis was conducted using tissue microarray samples of 174 primary tumors and 34 metastases of ovarian carcinoma, and the relationships between the protein expression, clinicopathological features and outcomes were investigated.ResultsA reduced E-cadherin expression was observed in 36.8% of the primary tumors and 30.4%, 35.7%, 37.7% and 52.7% of the stage I, II, III and IV tumors, respectively. The nuclear expression of Snail was positive in 33.9% of the primary tumors. The rate of an EMT-positive status, as represented by both a reduced E-cadherin expression and a nuclear expression of Snail, was significantly higher in the patients with peritoneal dissemination than in those without (p < 0.05). The EMT status was significantly associated with both the progression-free survival and overall survival (p <0.01). A multivariate analysis showed an EMT-positive status to be a significant predictor of both the progression-free survival (p < 0.05) and overall survival (P < 0.01).ConclusionsThese data indicate that the EMT status is significantly associated with peritoneal metastasis and both the progression-free survival and overall survival in patients with ovarian cancer. Therefore, clarifying and controlling EMT signaling is a promising approach to molecular targeted therapy for ovarian cancer.

The role of metastasis‐associated in colon cancer 1 (MACC1) in endometrial carcinoma tumorigenesis and progression

“…It is increasingly understood that endometrial carcinoma progression is closely related to the epithelial‐mesenchymal transition (EMT) . EMT, by which a cell changes phenotype from epithelial to one with mesenchymal properties, is an important step in cancer invasion and metastasis . EMT plays a key role in embryonic development and its importance in the pathogenesis of cancer and other human diseases is increasingly recognised.…”

“…one with mesenchymal properties, is an important step in cancer invasion and metastasis. [8][9][10][11][12] EMT plays a key role in embryonic development and its importance in the pathogenesis of cancer and other human diseases is increasingly recognised.…”

Snail‐mediated cancer stem cell‐like phenotype in human CNE2 nasopharyngeal carcinoma cell

“…In addition, Snail was reported to mediate epithelial‐mesenchymal transition and a CSC‐like phenotype, which enhanced cell invasion and migration in several human cancer cells, like colorectal cancer, aldehyde dehydrogenase (ALDH)‐negative thyroid cancer cells, and pancreatic cancer . In clinical settings, expression of Snail was found to be related to lymph node metastasis and poor prognosis in patients with gastric cancer, colorectal cancer, and ovarian cancer . There was also a report that nuclear Snail, but not cytoplasmic staining, predicts worse outcome in patients with NPC .…”

Biguanides in combination with olaparib limits tumorigenesis of drug‐resistant ovarian cancer cells through inhibition of Snail

“…25 Immunohistological analyses of both primary and metastatic ovarian carcinoma reveal that EMT is significantly associated with peritoneal metastasis and survival of ovarian cancer patients. 26 The correlation between EMT and aggressiveness of ovarian cancer is also supported by gene expression-based studies in which metastatic tumors generally exhibit mesenchymal signatures. 27 Poly (ADP ribose) polymerase (PARP) inhibitors (PARPi) are approved targeted therapeutics for breast and ovarian cancers bearing a germline BRCA1/2 mutation.…”