Prognostic association of starvation-induced gene expression in head and neck cancer

Sci Rep. 2021 Sep 27;11(1):19130. doi: 10.1038/s41598-021-98544-1.

Abstract

Autophagy-related genes (ARGs) have been implicated in the initiation and progression of malignant tumor promotion. To investigate the dynamics of expression of genes, including ARGs, head and neck squamous cell carcinoma (HNSCC) cells were placed under serum-free conditions to induce growth retardation and autophagy, and these starved cells were subjected to transcriptome analysis. Among the 21 starvation-induced genes (SIGs) located in the autophagy, cell proliferation, and survival signaling pathways, we identified SIGs that showed prominent up-regulation or down-regulation in vitro. These included AGR2, BST2, CALR, CD22, DDIT3, FOXA2, HSPA5, PIWIL4, PYCR1, SGK3, and TRIB3. The Cancer Genome Atlas (TCGA) database of HNSCC patients was used to examine the expression of up-regulated genes, and CALR, HSPA5, and TRIB3 were found to be highly expressed relative to solid normal tissue in cancer and the survival rate was reduced in patients with high expression. Protein-protein interaction analysis demonstrated the formation of a dense network of these genes. Cox regression analysis revealed that high expression of CALR, HSPA5, and TRIB3 was associated with poor prognosis in patients with TCGA-HNSCC. Therefore, these SIGs up-regulated under serum starvation may be molecular prognostic markers in HNSCC patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / genetics*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Calreticulin / analysis
  • Calreticulin / genetics
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Culture Media, Serum-Free
  • Datasets as Topic
  • Endoplasmic Reticulum Chaperone BiP / analysis
  • Endoplasmic Reticulum Chaperone BiP / genetics
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / mortality*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Prognosis
  • Protein Interaction Mapping
  • Protein Interaction Maps / genetics
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / antagonists & inhibitors
  • Protein Serine-Threonine Kinases / genetics
  • RNA-Seq
  • Repressor Proteins / analysis
  • Repressor Proteins / genetics
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / mortality*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Survival Rate
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • CALR protein, human
  • Calreticulin
  • Cell Cycle Proteins
  • Culture Media, Serum-Free
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Repressor Proteins
  • TRIB3 protein, human
  • Protein Serine-Threonine Kinases