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

Yasunori Uesato; Futoshi Kawamata; Shinichiro Ishino; Shinichiro Ono; Koichi Tamashiro; Hirofumi Koyama; Mitsuhisa Takatsuki

doi:10.21037/jgo-21-907

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

J Gastrointest Oncol. 2022 Jun;13(3):1384-1394. doi: 10.21037/jgo-21-907.

Authors

Yasunori Uesato¹, Futoshi Kawamata¹, Shinichiro Ishino¹, Shinichiro Ono¹, Koichi Tamashiro², Hirofumi Koyama², Mitsuhisa Takatsuki¹

Affiliations

¹ Department of Digestive and General Surgery, University of the Ryukyus, Okinawa, Japan.
² Department of Pathology, Okinawa Chubu Hospital, Okinawa, Japan.

Abstract

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.

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.

Keywords: Human chorionic gonadotropin free beta; epithelial mesenchymal transition; pancreatic cancer; pancreatic cell lines; transforming growth factor.