OGDHL Expression as a Prognostic Biomarker for Liver Cancer Patients

Dis Markers. 2019 Oct 17:2019:9037131. doi: 10.1155/2019/9037131. eCollection 2019.

Abstract

Background and objective: Liver cancer is a highly malignant tumor, and patients typically have poor prognoses. Metabolic reprogramming is a hallmark of cancer, and downregulation of oxoglutarate dehydrogenase-like (OGDHL) contributes to the onset and progression of several cancers. We examined the role of altered OGDHL expression in liver cancer and determined its value as a diagnostic and prognostic indicator for patients.

Material and methods: R (version 3.5.1) and several R extensions were used for data mining of The Cancer Genome Atlas (TCGA) dataset (including RNAseq and clinical information) and statistical analysis. Receiver operating characteristic analysis was used to determine the diagnostic value of OGDHL. The chi-squared test was used to identify the clinical correlates of OGDHL downregulation. Survival analysis (with the log-rank test) and univariate and multivariate Cox analysis were used to evaluate the effect of OGDHL expression on overall survival (OS) and relapse-free survival. TCGA was used for analysis of gene set enrichment.

Results: OGDHL had lower expression in cancerous liver tissues than noncancerous adjacent tissues, and low expression correlated with more advanced patient age, histologic grade, stage, T classification, and poor survival. Patients with lower OGDHL expression had shorter OS and relapse-free survival. Multivariate Cox regression indicated that low OGDHL expression was an independent risk factor for poor prognosis. Gene set enrichment analysis indicated enrichment of the mitotic spindle, G2M checkpoint, and E2F targets in the OGDHL low expression phenotype.

Conclusion: OGDHL has potential as a diagnostic and prognostic biomarker for liver cancer.

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ketoglutarate Dehydrogenase Complex / genetics*
  • Ketoglutarate Dehydrogenase Complex / metabolism
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Protein Subunits
  • ROC Curve
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • Protein Subunits
  • Ketoglutarate Dehydrogenase Complex