ArticleClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico2026
Integrated single-cell and bulk RNA sequencing reveals regulated necrosis-associated heterogeneity in pancreatic cancer.
Article in Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRegulated necrosis, a type of programmed cell death, is a major factor in cancer development. The function of regulated necrosis-related genes (RNRGs) in pancreatic cancer (PC) remains unclear. This study aimed to determine the heterogeneity associated with RNRGs in PC.
methodsSingle-cell RNA-seq was downloaded from the Gene Expression Omnibus database. Transcriptome profiling, somatic mutations, somatic copy-number alterations, and the clinical data of PC samples were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases.
resultsAt single-cell resolution, we discovered that the regulated necrosis status of non-malignant cells, rather than that of malignant cells, was a significant contributor. Notably, immune cells with immunosuppressive functions displayed higher regulated necrotic activity among distinct immune cells and clusters with discernible regulated necrosis traits. PCs were divided into two prognostic groups using signatures associated with regulated necrosis. Cluster 1 showed low regulated necrosis activity and a higher survival rate, whereas cluster 2 showed significant regulated necrosis activity and a lower survival rate. The clustering of TCGA cohorts mirrored the variety of intertumoral regulated necrosis, while ICGC cohorts further confirmed the intricacy. Finally, we discovered that the candidate gene for regulated necrotic activity in PC may be A2ML1.
conclusionsUsing a classifier that integrate single-cell and bulk RNA-seq, we identified the heterogeneity of RNRGs in PC. These results may deepen our understanding of RNRGs in PC, offer new perspectives for physicians to forecast prognoses, and help create more efficient and customized therapeutic approaches in the future.
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