Distinctive Metabolism-Associated Gene Clusters That Are Also Prognostic in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma

Abstract

Objective. To offer new prognostic evaluations by exploring potentially distinctive genetic features of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Methods. There were 12 samples for gene expression profiling processes in this study. These included three HCC lesion samples and their matched adjacent nontumor liver tissues obtained from patients with HCC, as well as three ICC samples and their controls collected similarly. In addition to the expression matrix generated on our own, profiles of other cohorts from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus (GEO) were also employed in later bioinformatical analyses. Differential analyses, functional analyses, protein interaction network analyses, and gene set variation analyses were used to identify key genes. To establish the prognostic models, univariate/multivariate Cox analyses and subsequent stepwise regression were applied, with the Akaike information criterion evaluating the goodness of fitness. Results. The top three pathways enriched in HCC were all metabolism-related; they were fatty acid degradation, retinol metabolism, and arachidonic acid metabolism. In ICC, on the other hand, additional pathways related to fat digestion and absorption and cholesterol metabolism were identified. Consistent characteristics of such a metabolic landscape were observed across different cohorts. A prognostic risk score model for calculating HCC risk was constructed, consisting of ADH4, ADH6, CYP2C9, CYP4F2, and RDH16. This signature predicts the 3-year survival with an AUC area of 0.708 ( 95 % CI = 0.644 to 0.772). For calculating the risk of ICC, a prognostic risk score model was built upon the expression levels of CYP26A1, NAT2, and UGT2B10. This signature predicts the 3-year survival with an AUC area of 0.806 (95% CI = 0.664 to 0.947). Conclusion. HCC and ICC share commonly abrupted pathways associated with the metabolism of fatty acids, retinol, arachidonic acids, and drugs, indicating similarities in their pathogenesis as primary liver cancers. On the flip side, these two types of cancer possess distinctive promising biomarkers for predicting overall survival or potential targeted therapies.

Development and validation of a coagulation-related genes prognostic model for hepatocellular carcinoma

“…CYP2C9 is a member of the cytochrome P2C (CYP2C) family and is involved in clinical drug metabolism. The low expression of CYP2C9 and LCAT in HCC is associated with poor prognosis [20][21][22]. Nevertheless, the research on the expression of CENPE in HCC samples and its clinical relevance is very limited.…”

Eicosanoids and other oxylipins in liver injury, inflammation and liver cancer development

“…Previous studies have established that etiologies such as ALD and cirrhosis have isoform specificities in their impact on CYP metabolism ( Marino et al, 1998 ; Yang et al, 2003 ) with CYP2C and CYP2D being the most altered between healthy controls and liver disease cohorts ( Frye et al, 2006 ). In HCC, Cyp enzymes responsible for PUFA metabolism have been identified among the top genes enriched in a study aimed at elucidating prognostic markers ( Ding et al, 2022 ). This study also identified CYP26A1, CYP2C9 and CYP4F2 among a proposed prognostic panel of genes when trying to model the risks for iCCA and HCC ( Ding et al, 2022 ).…”

“…In HCC, Cyp enzymes responsible for PUFA metabolism have been identified among the top genes enriched in a study aimed at elucidating prognostic markers ( Ding et al, 2022 ). This study also identified CYP26A1, CYP2C9 and CYP4F2 among a proposed prognostic panel of genes when trying to model the risks for iCCA and HCC ( Ding et al, 2022 ). In a separate cohort, the expression of CYP2A6 was also closely associated with tumor grades and favorable prognosis ( Jiang et al, 2021 ).…”

Signature construction and molecular subtype identification based on liver-specific genes for prediction of prognosis, immune activity, and anti-cancer drug sensitivity in hepatocellular carcinoma

“…A variety of liver-specific genes (LSGs) were presented to be associated with HCC development and progression. For instance, RDH16 was shown to be downregulated in HCC and associated with HCC survival [ 14 , 15 ]. Inverse association of SLC10A1 with HCC occurrence and progression were reported [ 16 ].…”