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Multi-omics Insights into PDHA1 as a Predictive Biomarker for Prognosis, Immunotherapy Efficacy, and Drug Sensitivity in Hepatocellular Carcinoma

  • 0Department of Infectious Diseases, Zhoushan Hospital, Wenzhou Medical University, Zhoushan 316021, China.
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November 25, 2024

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November 25, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Pyruvate dehydrogenase E1 alpha subunit (PDHA1) indicates poor prognosis in hepatocellular carcinoma (HCC). Higher PDHA1 expression correlates with immune infiltration and predicts sensitivity to chemotherapy drugs like 5-fluorouracil.

Area Of Science

  • Oncology
  • Metabolic Reprogramming
  • Cancer Biomarkers

Background

  • Metabolic reprogramming is crucial in tumor progression, with PDHA1 (Pyruvate Dehydrogenase E1 Alpha Subunit) playing a role.
  • The clinical significance of PDHA1 in hepatocellular carcinoma (HCC), particularly for predicting drug sensitivity, remains underexplored.

Purpose Of The Study

  • To investigate the clinical value of PDHA1 expression in HCC.
  • To assess PDHA1's role in predicting prognosis and drug sensitivity in HCC patients.

Main Methods

  • Analysis of PDHA1 expression in HCC tissues versus normal tissues.
  • Correlation analysis of PDHA1 expression with immune cell infiltration using multiple algorithms (TIMER, XCell, MCPCOUNTER, CIBERSORT, EPIC, QUANTISEQ) and single-cell RNA-sequencing.
  • Investigation of PDHA1 association with immune checkpoint genes.
  • Prognostic analysis using univariate and multivariate Cox regression and nomogram construction.
  • Assessment of PDHA1's link to drug sensitivity (5-fluorouracil, gemcitabine, paclitaxel, sorafenib) and molecular docking.

Main Results

  • PDHA1 expression was significantly higher in HCC tissues and associated with poor patient prognosis.
  • PDHA1 expression positively correlated with immune cell infiltration and immune checkpoint genes.
  • PDHA1 served as an independent prognostic indicator for HCC, with a nomogram showing strong predictive power.
  • Elevated PDHA1 expression predicted increased sensitivity to 5-fluorouracil, gemcitabine, paclitaxel, and sorafenib.

Conclusions

  • PDHA1 is a potential prognostic biomarker in HCC, linked to immune infiltration.
  • PDHA1 expression can predict sensitivity to several key chemotherapeutic agents used in HCC treatment.
  • Targeting PDHA1 may offer therapeutic strategies for improving HCC patient outcomes.