Tumor microenvironment derived signature predicting relapse-free survival in I-III cancer and preliminary experiment verification

Int Immunopharmacol. 2021 Feb:91:107243. doi: 10.1016/j.intimp.2020.107243. Epub 2020 Dec 13.

Abstract

The recurrence in colon cancer contributed to great difficulties in diagnostic and therapeutic treatment. Tumor microenvironment (TME) gains increasing attention recently. After univariate Cox analysis on relapse-free survival (RFS) and ESTIMATE analysis, WGCNA was further conducted to determine the TME and relapse-related genes in I-III colon cancer. Functional enrichment analyses were conducted. Furthermore, seven genes were screened to build a prognostic signature via LASSO and multivariate Cox analysis. Univariate followed multivariate Cox analysis all showed that the risk group calculated by the signature as a significant predictors. The ROC curves showed great prognostic in the internal training group, internal verification group, and independent external verification group. In the training group, the AUC at 1, 3, and 5 years was 0.737, 0.79, and 0.756. In addition, correlation analysis presented that the signature and genes involved in were significantly associated with the TME. Moreover, 3 of 7 genes (FAM78A, SGIP1, and MMP9) were validated to be associated with PDL1 through qRT-PCR.

Keywords: Colon cancer; Relapse-free survival analysis; tumor environment (TME); weighted gene co-expression network analysis (WGCNA).

Publication types

  • Validation Study

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Aged
  • B7-H1 Antigen / genetics
  • Biomarkers, Tumor / genetics*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / mortality
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / surgery
  • Databases, Genetic
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks
  • Humans
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Predictive Value of Tests
  • Preliminary Data
  • Reproducibility of Results
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transcriptome*
  • Treatment Outcome
  • Tumor Microenvironment / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • SGIP1 protein, human
  • MMP9 protein, human
  • Matrix Metalloproteinase 9