Abstract
Hepatocellular carcinoma (HCC) is a deadly tumor with high heterogeneity. Aerobic glycolysis is a common indicator of tumor growth and plays a key role in tumorigenesis. Heterogeneity in distinct metabolic pathways can be used to stratify HCC into clinically relevant subgroups, but these have not yet been well-established. In this study, we constructed a model called aerobic glycolysis index (AGI) as a marker of aerobic glycolysis using genomic data of hepatocellular carcinoma from The Cancer Genome Atlas (TCGA) project. Our results showed that this parameter inferred enhanced aerobic glycolysis activity in tumor tissues. Furthermore, high AGI is associated with poor tumor differentiation and advanced stages and could predict poor prognosis including reduced overall survival and disease-free survival. More importantly, the AGI could accurately predict tumor sensitivity to Sorafenib therapy. Therefore, the AGI may be a promising biomarker that can accurately stratify patients and improve their treatment efficacy.
Highlights
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths [1]
The Gene Set Enrichment Analysis (GSEA) results revealed that the glycolysis signaling pathway was significantly enriched in hepatocellular carcinoma (HCC) tumor tissues compared with normal tissues (Figure 2B)
The results demonstrated that the aerobic glycolysis index (AGI) correlated closely to these genes (HK2, r = 0.43, P < 2.2e−16; PFKP, r = 0.39, P = 1.4e−14; PFKFB3, r = 0.27, P = 2e−7; pyruvate kinase M1/2 (PKM2), r = 0.66, P < 2e−16), as shown in Supplementary Figure 3
Summary
Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths [1]. Despite advances in the treatment of HCC, its prognosis remains unsatisfactory, with a 5-year overall survival (OS) rate of 25–55% [2,3,4]. Distal metastasis, and resistance to conventional therapy are the leading causes of HCC progression into late-stage cancer with limited treatment options. Chromosomal instability, epigenetic changes, and molecular signaling pathway dysregulation are reported causes of hepatocellular carcinogenesis [5]. Advances in the field of molecular oncology are urgently required to improve the prognosis of HCC.
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