B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

Cell Physiol Biochem. 2018;45(1):237-249. doi: 10.1159/000486770. Epub 2018 Jan 22.

Abstract

Background/aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin) and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC) and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo.

Results: Fifty out of 136 CRC patients (37%) expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031) and lymph node metastasis (P=0.012). Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289). β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227). Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells.

Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT).

Keywords: Early-stage CRC; Epithelial-Mesenchymal Transition (EMT); Invasion; Prognosis; β-HCG.

MeSH terms

  • Aged
  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chorionic Gonadotropin, beta Subunit, Human / deficiency
  • Chorionic Gonadotropin, beta Subunit, Human / genetics
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Severity of Illness Index
  • Transplantation, Heterologous

Substances

  • Chorionic Gonadotropin, beta Subunit, Human