A 16-mRNA signature optimizes recurrence-free survival prediction of Stages II and III gastric cancer

J Cell Physiol. 2020 Jul;235(7-8):5777-5786. doi: 10.1002/jcp.29511. Epub 2020 Feb 11.

Abstract

High-throughput messenger RNA (mRNA) analysis has become a powerful tool for exploring tumor recurrence or metastasis mechanisms. Here, we constructed a signature to predict the recurrence risk of Stages II and III gastric cancer (GC) patients. A least absolute shrinkage and selection operator method Cox regression model was utilized to construct the signature. Using this method, a 16-mRNA signature was identified to be associated with the relapse-free survival of Stages II and III GCs in training dataset GSE62254 (n = 194). Then this signature was validated in an independent Gene Expression Omnibus cohort GSE26253 (n = 297) and a dataset of The Cancer Genome Atlas (TCGA; n = 235). This classifier could successfully screen out the high-risk Stages II and III GCs in the training cohort (hazard ratio [HR] = 40.91; 95% confidence interval [CI] = 5.58-299.7; p < .0001). Analysis in two independent validation cohorts yielded consistent results (GSE26253: HR = 1.69, 95% CI = 1.17-2.43,; p = .0045; TCGA: HR = 2.01, 95% CI = 1.13-3.56, p = .0146). Cox regression analyses revealed that the risk score derived from this signature was an independent risk factor in Stages II and III GCs. Besides, a nomogram was constructed to serve clinical practice. Through gene set variation analysis, we found several gene sets associated with chemotherapeutic drug resistance and tumor metastasis significantly enriched in high-risk patients. In summary, this 16-mRNA signature can be used as a powerful tool for prognostic evaluation and help clinicians identify high-risk patients.

Keywords: LASSO; gastric cancer; relapse-free survival; signature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Proteins
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Nomograms
  • Prognosis
  • RNA, Messenger / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Transcriptome

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • RNA, Messenger