Human chorionic gonadotropin-β promotes pancreatic cancer progression via the epithelial mesenchymal transition signaling pathway

人绒毛膜促性腺激素-β通过上皮间质转化信号通路促进胰腺癌进展

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作者:Yasunori Uesato, Futoshi Kawamata, Shinichiro Ishino, Shinichiro Ono, Koichi Tamashiro, Hirofumi Koyama, Mitsuhisa Takatsuki

Background

The human chorionic gonadotropin free beta-subunit (hCGβ) is ectopically produced in various epithelial cancers and is associated with poor prognoses. However, its molecular mechanism remains unclear. In this study, we examined the biological role of hCGβ in pancreatic cancer progression.

Conclusions

hCGβ expression is related to cancer progression and poor prognoses via epithelial mesenchymal transition. hCGβ is a potential prognostic marker and molecular target in pancreatic cancer.

Methods

Tissue specimens of 30 patients with pancreatic cancer were examined immunohistochemically to investigate the relationship between hCGβ expression and clinicopathological features. We also evaluated the molecular effects of hCGβ-downregulated pancreatic cell lines.

Results

Total of 21 cases were positive for immunostaining, and 17 of 25 metastatic lymph nodes were positive. hCGβ expression levels were correlated with pancreatic cancer T and N factors. hCGβ expression was significantly associated with poor overall and recurrence-free survival (P<0.001). In a multivariate analysis, hCGβ expression was independently associated with overall survival (HR 14.0; 95% CI: 1.5-130; P=0.019). The proliferative, invasive, and migratory abilities of hCGβ-downregulated cell lines were reduced compared with the control cell lines. Moreover, downregulation of hCGβ reduced vimentin, slug, and α-smooth muscle actin expression and increased E-cadherin expression. Conclusions: hCGβ expression is related to cancer progression and poor prognoses via epithelial mesenchymal transition. hCGβ is a potential prognostic marker and molecular target in pancreatic cancer.

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