Pentose-phosphate pathway reveals complex tumor-promoting features, immunity characteristics, and drug response in human cancers

作者：Xinyu Huang, Lingyan Deng, Xiong Wang, Wenhua Liu, Peng Wang, Na Shen · 发表于：Oncology and Translational Medicine · 年份：2025 · DOI：10.1097/ot9.0000000000000079 · 被引用次数：3 · 研究领域：Ferroptosis and cancer prognosis、Cancer Research and Treatments、Cancer-related Molecular Pathways

Abstract Background The pentose-phosphate pathway (PPP) plays a vital role in cell growth and metabolic reprogramming. However, its role in human cancer remains unclear. Methods We conducted a systematic analysis to investigate the complex and crucial roles of the PPP using multi-omics data from more than 10,000 samples across 33 cancer types sourced from multiple databases, including the Molecular Signature Databases, The Cancer Genome Atlas, and Cancer Single-cell State Atlas. Independent cohorts such as IMvigor210 and Liver Cancer-RIKEN, Japan Project from International Cancer Genome Consortium (ICGC-LIRI-JP). Results PPP-related genes were upregulated in most cancers, a phenomenon possibly driven by copy number variation and DNA methylation. Single-cell analysis revealed significant tumor-promoting features of PPP. We developed a PPP activity score to quantify the overall expression of PPP-related genes. PPP activity scores were significantly correlated with multiple hallmark pathways, the tumor microenvironment, cancer stemness, and immune-related signatures. Drug analysis revealed that high PPP activity scores contributed to resistance to drug-targeting pathways, including PI3K/mTOR, RTK, and TP53 signaling. In addition, PPP activity scores are potential predictors of immunotherapy outcomes. Prognostic analysis revealed that whereas individual PPP-related genes had varying effects on survival, high PPP activity scores were generally associated with poor prognosis, parti...