Research Paper Volume 12, Issue 11 pp 10300—10316
Alterations in glycolytic/cholesterogenic gene expression in hepatocellular carcinoma
- 1 Department of Health Management, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- 2 Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- 3 Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Afﬁliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- 4 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- 5 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
Received: February 27, 2020 Accepted: April 20, 2020 Published: June 1, 2020https://doi.org/10.18632/aging.103254
How to Cite
Copyright © 2020 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Metabolic reprogramming is a hallmark of tumors, including hepatocellular carcinoma (HCC). We used data from The Cancer Genome Atlas and the International Cancer Genome Consortium to assess the alterations in glycolytic and cholesterogenic genes in HCC and to determine their association with clinical features in HCC patients. Based on the gene expression profiles from these databases, we established four subtypes of HCC: cholesterogenic, glycolytic, mixed, and quiescent. The prognosis of the cholesterogenic subgroup was poorer than that of the glycolytic group. Tumors in the glycolytic group were more sensitive to chemotherapy. We also explored the relationships between these metabolic subtypes and previously established HCC subgroups. Glycolytic gene expression correlated strongly with poorer prognostic gene expression in the Hoshida classification of HCC. Whole-genome analyses indicated that aberrant amplification of TP53 and MYC in HCC were associated with abnormal anabolic cholesterol metabolism. The mRNA levels of mitochondrial pyruvate carriers 1 and 2 differed among the HCC metabolic subtypes. In a bioinformatics analysis we identified genomic characteristics of tumor metabolism that varied among different cancer types. These findings demonstrate that metabolic subtypes may be valuable prognostic indicators in HCC patients.
HCC: hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; ICGC: International Cancer Genome Consortium; SNVs: single nucleotide variations; CNVs: copy number variations; LIHC: liver hepatocellular carcinoma; BH: Benjamini-Hochberg; CESC: cervical squamous cell carcinoma; GBM: glioblastoma multiforme; KIRC: kidney renal clear cell carcinoma; LGG: brain lower grade glioma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; STAD: stomach adenocarcinoma; SARC: sarcoma.