Frontiers in Pharmacology (Oct 2022)

Prognostic value of antitumor drug targets prediction using integrated bioinformatic analysis for immunogenic cell death-related lncRNA model based on stomach adenocarcinoma characteristics and tumor immune microenvironment

  • Dayong Ding,
  • Yan Zhao,
  • Yanzhuo Su,
  • Huaixi Yang,
  • Xuefeng Wang,
  • Lin Chen

DOI
https://doi.org/10.3389/fphar.2022.1022294
Journal volume & issue
Vol. 13

Abstract

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Stomach adenocarcinoma (STAD) ranks as the fourth prevalent cause of mortality worldwide due to cancer. The prognosis for those suffering from STAD was bleak. Immunogenic cell death (ICD), a form of induced cellular death that causes an adaptive immune response and has increasing in anticancer treatment. However, it has not been ascertained how ICD-related lncRNAs affect STAD. Using univariate Cox regression and the TCGA database, lncRNAs with prognostic value were identified. Thereafter, we created a prognostic lncRNA-based model using LASSO. Kaplan-Meier assessment, time-dependent receiver operating characteristic (ROC) analyzation, independent prognostic investigation, and nomogram were used to assess model correctness. Additional research included evaluations of the immunological microenvironment, gene set enrichment analyses (GSEA), tumor mutation burdens (TMBs), tumor immune dysfunctions and exclusions (TIDEs), and antitumor compounds IC50 predictions. We found 24 ICD-related lncRNAs with prognostic value via univariate Cox analysis (p < 0.05). Subsequently, a risk model was proposed using five lncRNAs relevant to ICD. The risk signature, correlated with immune cell infiltration, had strong predictive performance. Individuals at low-risk group outlived those at high risk (p < 0.001). An evaluation of the 5-lncRNA risk mode including ROC curves, nomograms, and correction curves confirmed its predictive capability. The findings of functional tests revealed a substantial alteration in immunological conditions and the IC50 sensitivity for the two groups. Using five ICD-related lncRNAs, the authors developed a new risk model for STAD patients that could predict their cumulative overall survival rate and guide their individual treatment.

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