Identification and validation of candidate clinical signatures of apolipoprotein L isoforms in hepatocellular carcinoma

Sci Rep. 2023 Nov 28;13(1):20969. doi: 10.1038/s41598-023-48366-0.

Abstract

Hepatocellular carcinoma (HCC) is a lethal malignancy worldwide with an increasing number of new cases each year. Apolipoprotein (APOL) isoforms have been explored for their associations with HCC.The GSE14520 cohort was used for training data; The Cancer Genome Atlas (TCGA) database was used for validated data. Diagnostic, prognostic significance and mechanisms were explored using these cohorts. Risk score models and nomograms were constructed using prognosis-related isoforms and clinical factors for survival prediction. Oncomine and HCCDB databases were further used for validation of diagnostic, prognostic significance. APOL1, 3, and 6 were differentially expressed in two cohorts (all P ≤ 0.05). APOL1 and APOL6 had diagnostic capacity whereas APOL3 and APOL6 had prognostic capacity in two cohorts (areas under curves [AUCs] > 0.7, P ≤ 0.05). Mechanism studies demonstrated that APOL3 and APOL6 might be involved in humoral chemokine signaling pathways (all P ≤ 0.05). Risk score models and nomograms were constructed and validated for survival prediction of HCC. Moreover, diagnostic values of APOL1 and weak APOL6 were validated in Oncomine database (AUC > 0.700, 0.694); prognostic values of APOL3 and APOL6 were validated in HCCDB database (all P < 0.05). Differentially expressed APOL1 and APOL6 might be diagnostic biomarkers; APOL3 and APOL6 might be prognostic biomarkers of RFS and OS for HCC via chemokine signaling pathways.

MeSH terms

  • Apolipoprotein L1 / genetics
  • Biomarkers
  • Carcinoma, Hepatocellular* / diagnosis
  • Carcinoma, Hepatocellular* / genetics
  • Chemokines
  • Humans
  • Liver Neoplasms* / diagnosis
  • Liver Neoplasms* / genetics
  • Prognosis
  • Protein Isoforms

Substances

  • Apolipoprotein L1
  • Protein Isoforms
  • Biomarkers
  • Chemokines
  • APOL1 protein, human