Identification of prognostic biomarkers for patients with hepatocellular carcinoma after hepatectomy

Abstract

Hepatocellular carcinoma (HCC) is a lethal malignancy with high morbidity and mortality rates worldwide. The identification of prognosis-associated biomarkers is crucial to improve HCC patient survival. The present study aimed to explore potential predictive biomarkers for HCC. Differentially expressed genes (DEGs) were analyzed in the GSE36376 dataset using GEO2R. Hub genes were identified and further investigated for prognostic value in HCC patients. A risk score model and nomogram were constructed to predict HCC prognosis using the prognosis-associated genes and clinical factors. Pearson's correlation was employed to show interactions among hub genes. Gene enrichment analysis was performed to identify detailed biological processes and pathways. A total of 71 DEGs were obtained and seven (ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13, all adjusted P≤0.05) of the 10 hub genes were identified as prognosis-related genes for survival analysis in HCC patients, including alcohol dehydrogenase 4 (class II), pi polypeptide (ADH4), cytochrome p450 family 2 subfamily C member 8 (CYP2C8), cytochrome P450 family 2 subfamily C member 9 (CYP2C9), cytochrome P450 family 8 subfamily B member 1 (CYP8B1), solute carrier family 22 member 1 (SLC22A1), tyrosine aminotransferase (TAT) and hydroxysteroid 17-β dehydrogenase 13 (HSD17B13). The risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The majority of genes showed significant Pearson's correlations with others (41 Pearson correlations P≤0.01, four Pearson correlations P>0.05). GO analysis revealed that terms such as ‘chemical carcinogenesis’ and ‘drug metabolism-cytochrome P450’ were enriched and may prove helpful to elucidate the mechanisms of hepatocarcinogenesis. Hub genes ADH4, CYP2C8, CYP2C9, CYP8B1, SLC22A1, TAT and HSD17B13 may be useful as predictive biomarkers for HCC prognosis.

A guide to plasma membrane solute carrier proteins

“…As one of the largest families of solute carriers, SLC22 proteins and their transport substrates have a wide range of roles in the development and progression of cancer. Members of this family have been found to be both downregulated (SLC22A1, SLC22A2, SLC22A11) and upregulated (SLC22A3 and SLC22A18) in the tissue of pancreatic and liver cancer patients with the different transport proteins having varying effects on the long-term survival of proteins [443][444][445][446]. As organic ion transporters, the SLC22 family of proteins plays a particularly important role in the transport of drugs across cell membranes [416].…”

<p>The Perspective of Diagnostic and Prognostic Values of Lipoxygenases mRNA Expression in Colon Adenocarcinoma</p>

“…org). 35 Then we explored the gene interactions using online tools of the Gene Multiple Association Network Integration Algorithm (GeneMANIA, http://www.genema nia.org/, obtained June 27, 2019) 36,37 and Search Tool for the Retrieval of Interacting Genes (STRING, https://stringdb.org/, obtained June 27, 2019) 38,39 at the levels of gene and protein.…”

Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

“…CYP2B6 also plays a crucial part in the progression of prostate cancer and may serve as a prognostic predictor for this malignancy [44]. CYP2C8 and CYP2C9 are downregulated in patients with HCC and regarded as candidate prognostic biomarker for this disease [45] and for patients with HCC following hepatectomy [46]. The proliferation of esophageal cancer is e ciently inhibited in patients with highly expressed CYP2C9 [47].…”