Biological Characteristics and Clinical Significance of ITGB1 and RHOC in Patients With Recurrent Colorectal Cancer

Anticancer Res. 2019 Sep;39(9):4853-4864. doi: 10.21873/anticanres.13671.

Abstract

Background/aim: Colorectal cancer (CRC) is the leading cause of cancer mortality worldwide. Its poor prognosis can be ascribed primarily to high recurrence rates. Accordingly, the aim of this study was to identify novel prognostic biomarkers and therapeutic targets for management of CRC.

Materials and methods: To develop prognostic biomarkers, we performed RNA-seq analysis and real-time RT-PCR in primary cancer tissues with or without systemic recurrence. To characterize the molecular functions of the encoded proteins, CRC cells underexpressing or overexpressing the candidate genes were established and appropriate cell-based assays were applied.

Results: ITGB1 and RHOC mRNA levels were up-regulated in the recurrence group of CRC patients. Overexpression of ITGB1 or RHOC stimulated CRC cell proliferation, invasion and migration, whereas the opposite effects were observed in cells underexpressing either protein. Five-year recurrence-free survival rates were significantly higher in the ITGB1- and RHOC-underexpression groups than those in the overexpression.

Conclusion: ITGB1 and RHOC are potential predictors of recurrence and therapeutic targets for CRC, possibly predicting a high-risk group of stage II patients.

Keywords: Colorectal cancer; ITGB1; RHOC; predictive marker; recurrence.

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Humans
  • Integrin beta1 / metabolism*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • RNA, Small Interfering / genetics
  • Recurrence
  • Survival Analysis
  • rhoC GTP-Binding Protein / metabolism*

Substances

  • Biomarkers, Tumor
  • Integrin beta1
  • RNA, Small Interfering
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • RHOC protein, human
  • rhoC GTP-Binding Protein