Alterations in genes involved in glycolysis and hypoxia affect the prognosis of pancreatic cancer

• Published in: Heliyon 2024-07, Vol.10 (14), p.e34104, Article e34104
• Main Authors: Zou, Jiayue, Zhu, Qilu, Sun, Yizhang, Zhang, Weigang, Huang, Yujie
• Format: Article
• Language: English
• Subjects: Biomarkers; Glycolysis; Hypoxia; Pancreatic cancer; Prognosis
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2024.e34104

To construct a prognostic model for pancreatic cancer based on glycolytic and hypoxic metabolic subtypes. To analyze the biological characteristics of these subtypes and explore potential therapeutic options. We obtained mRNA, simple nucleotide variation (SNP), and clinical data for pancreatic cancer from The Cancer Genome Atlas (TCGA). Patients were classified into four metabolic subtypes. We focused on glycolysis and hypoxia subtypes. Single-sample gene set enrichment analysis (ssGSEA) assessed immune cell infiltration. We evaluated the effects of immunotherapy and chemotherapy on these subtypes. Cox regression and random survival forest algorithms were used to build a prognostic model. Validation was performed using data from the International Cancer Genome Consortium (ICGC) and ArrayExpress database. We identified four subtypes. Kaplan-Meier survival analysis showed the glycolytic subtype had the longest survival, while the hypoxic subtype had the shortest. The glycolytic subtype exhibited higher immune cell infiltration. Immunotherapy and chemotherapy appeared more beneficial for the glycolytic subtype. KRAS mutations were more frequent in the hypoxic subtype. Our prognostic model indicated a worse prognosis for high-risk groups, validated by external data. The glycolytic metabolic subtype of pancreatic cancer is associated with longer survival and better response to chemotherapy and immunotherapy compared to the hypoxic subtype. •Prognostic Model: Developed and validated a prognostic model for pancreatic cancer based on glycolytic and hypoxic subtypes.•Survival Analysis: Found that the glycolytic subtype had the longest survival, while the hypoxic subtype had the shortest.•Immune Response: Glycolytic subtype showed higher immune cell infiltration and better response to anti-PD-1 therapy and certain chemotherapeutic agents.•KRAS Mutations: Identified higher frequency of KRAS mutations in the hypoxic subtype, correlating with poorer prognosis.•External Validation: The model was validated with significant prognostic value using external datasets from ICGC and ArrayExpress.