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Updated: Jun 6, 2026
Pancreatic Tissue Dissection to Isolate Viable Single Cells
Published on: May 26, 2023
Integrated single-cell and bulk RNA sequencing reveals regulated necrosis-associated heterogeneity in pancreatic
Lei Feng1,2, Jianmin Zhang3, Zhonghui Zhu4
1Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550001, Guizhou, China. fenglei10806@163.com.
Background:
Regulated 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.
Methods:
Single-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.
Results:
At 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.
Conclusions:
Using 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.
Insights
Regulated necrosis-related genes (RNRGs) in pancreatic cancer (PC) show significant heterogeneity, particularly in non-malignant and immune cells. This heterogeneity impacts patient prognosis, with high necrosis activity linked to poorer survival rates.
Area of Science:
- Oncology
- Cell Biology
- Genomics
Background:
- Regulated necrosis, a form of programmed cell death, plays a role in cancer development.
- The specific involvement of regulated necrosis-related genes (RNRGs) in pancreatic cancer (PC) is not well understood.
- This study investigates the heterogeneity of RNRGs within PC.
Purpose of the Study:
- To elucidate the heterogeneity of regulated necrosis-related genes (RNRGs) in pancreatic cancer (PC).
- To explore the prognostic implications of RNRG expression patterns in PC.
- To identify potential therapeutic targets based on RNRG heterogeneity.
Main Methods:
- Utilized single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus database.
- Analyzed transcriptome profiling, somatic mutations, and copy-number alterations from TCGA and ICGC databases.
- Developed a classifier integrating single-cell and bulk RNA-seq data.
Main Results:
- Regulated necrosis status in non-malignant cells, especially immunosuppressive immune cells, significantly contributed to PC heterogeneity.
- PCs were classified into two prognostic groups based on regulated necrosis activity: low activity correlated with better survival, while high activity correlated with poorer survival.
- Identified A2ML1 as a candidate gene associated with regulated necrotic activity in PC.
Conclusions:
- Heterogeneity of RNRGs in PC was identified using an integrated scRNA-seq and bulk RNA-seq classifier.
- Findings enhance understanding of RNRGs in PC, offering new prognostic insights for physicians.
- Results pave the way for developing more personalized and effective therapeutic strategies for PC.
