Dataset Information

The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma.

ABSTRACT: Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surrounding microenvironment. Signaling pathways that drive PC cell growth have been the subject of intense scrutiny and interest has been attracted by necroptosis, a distinct type of programmed cell death. In this review, we provide a historical background on necroptosis and a detailed analysis of the ongoing debate on the role of necroptosis in PC malignant progression.

SUBMITTER: Giansante V

PROVIDER: S-EPMC10454309 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma.

Giansante Valentina V Stati Gianmarco G Sancilio Silvia S Guerra Emanuela E Alberti Saverio S Di Pietro Roberta R

International journal of molecular sciences 20230810 16

Pancreatic cancer (PC) is the seventh leading cause of cancer-related death. PC incidence has continued to increase by about 1% each year in both men and women. Although the 5-year relative survival rate of PC has increased from 3% to 12%, it is still the lowest among cancers. Hence, novel therapeutic strategies are urgently needed. Challenges in PC-targeted therapeutic strategies stem from the high PC heterogeneity and from the poorly understood interplay between cancer cells and the surroundin ...[more]

PMID: 37628814

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Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors with a poor prognosis. Recently, necroptosis has been reported to participate in the progression of multiple tumors. However, few studies have revealed the relationship between necroptosis and PDAC, and the role of necroptosis in PDAC has not yet been clarified. Methods: The mRNA expression data and corresponding clinical information of PDAC patients were downloaded from the TCGA and GEO databases. The necroptosis-related genes (NRGs) were obtained from the CUSABIO website. Consensus clustering was performed to divide PDAC patients into two clusters. Univariate and LASSO Cox regression analyses were applied to screen the NRGs related to prognosis to construct the prognostic model. The predictive value of the prognostic model was evaluated by Kaplan-Meier survival analysis and ROC curve. Univariate and multivariate Cox regression analyses were used to evaluate whether the risk score could be used as an independent predictor of PDAC prognosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and single-sample gene set enrichment analysis (ssGSEA) were used for functional enrichment analysis. Finally, using qRT-PCR examined NRGs mRNA expression in vitro. Results: Based on the TCGA database, a total of 22 differential expressed NRGs were identified, among which eight NRGs (CAPN2, CHMP4C, PLA2G4F, PYGB, BCL2, JAK3, PLA2G4C and STAT4) that may be related to prognosis were screened by univariate Cox regression analysis. And CAPN2, CHMP4C, PLA2G4C and STAT4 were further selected to construct the prognostic model. Kaplan-Meier survival analysis and ROC curve showed that there was a significant correlation between the risk model and prognosis. Univariate and multivariate Cox regression analyses showed that the risk score of the prognostic model could be used as an independent predictor. The model efficacy was further demonstrated in the GEO cohort. Functional analysis revealed that there were significant differences in immune status between high and low-risk groups. Finally, the qRT-PCR results revealed a similar dysregulation of NRGs in PDAC cell lines. Conclusion: This study successfully constructed and verified a prognostic model based on NRGs, which has a good predictive value for the prognosis of PDAC patients.

Dataset Information

The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma.

Publications

The Dual Role of Necroptosis in Pancreatic Ductal Adenocarcinoma.

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