High expression of tumor susceptibility gene 101 (TSG101) is associated with more aggressive behavior in colorectal carcinoma

J Cancer Res Clin Oncol. 2021 Jun;147(6):1631-1646. doi: 10.1007/s00432-021-03561-2. Epub 2021 Feb 22.

Abstract

Introduction: Identification of genetic determinants such as exosomal content that drives progression and metastasis of colorectal cancer (CRC) has received considerable attention. The present study aims to identify a suitable biomarker in CRC tissues and exosomes based on bioinformatics data to evaluate its expression patterns in CRC tissues as well as its clinicopathological significance.

Materials and methods: Protein-protein interaction (PPI) network and enrichment analysis were applied to identify up-regulated genes that contributed in CRC exosomes to select the marker. The expression patterns and clinical significance of selected exosomal marker were evaluated in tissue microarrays (TMAs) of 445 CRC tumors and 39 adjacent normal tissues using immunohistochemistry method.

Results: Based on bioinformatics data, TSG101 gene was prominent amongst the tumor tissues and exosomes. Expression of TSG101 was significantly up-regulated in tumor cells compared to adjacent normal tissues (p-value = 0.04). Moreover, higher expressions of TSG101 (cytoplasmic and nuclear) were significantly associated with tumor differentiation (p-value = 0.042) and distant metastasis (p-value = 0.027). A significant association was found in the cytoplasmic expression of TSG101 between well and moderate tumor differentiation (p-value = 0.005) as well as moderate and poor differentiation (p-value = 0.050).

Conclusion: These findings indicate that the exploration of crosstalk between exosome content and CRC may be valuable for the development of novel exosomal biomarkers. Increased expression of TSG101, as a promising exosome marker, is more associated with more aggressive tumor behaviors, metastasis, and progression of CRC, which paves the way for therapeutic strategies and CRC management. However, further investigations are warranted to clarify the molecular mechanisms of TSG101 in CRC.

Keywords: Colorectal cancer; Immunohistochemistry (IHC); TSG101; Tissue microarray (TMA).

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism
  • Carcinoma / diagnosis
  • Carcinoma / metabolism
  • Carcinoma / mortality
  • Carcinoma / pathology*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Cross-Sectional Studies
  • DNA-Binding Proteins / metabolism*
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Iran
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Protein Interaction Mapping
  • Tissue Array Analysis
  • Transcription Factors / metabolism*
  • Up-Regulation
  • Young Adult

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Transcription Factors
  • Tsg101 protein