AI Article Synopsis
- - Ferroptosis is a type of programmed cell death that could be a promising strategy for treating pancreatic adenocarcinoma (PAAD), but the roles of ferroptosis-related genes in this context are not fully understood.
- - A study created a novel risk signature from six ferroptosis-related genes and determined that it could independently predict patient outcomes, showing potential for improving clinical decision-making.
- - Further analyses indicated that high ferroptosis risk levels impacted immune cell presence but did not significantly alter immune pathways, and specific gene silencing experiments showed that two genes, PTGS2 and SQLE, played a role in tumor cell behaviors and epithelial to mesenchymal transition.
Article Abstract
Ferroptosis, a new form of programmed cell death, provides a new option for anti-tumor treatment. However, the roles of ferroptosis-related (FR) genes in pancreatic adenocarcinoma (PAAD) were not fully elaborated. In the present study, 185 TCGA samples and 81 ICGC samples were used as training and validation cohorts, respectively. A novel FR risk signature (ALOX5, ALOX12, PTGS2, SAT1, STEAP3 and SQLE) was constructed via the Lasso regression analysis. In TCGA cohort, the risk signature was identified as an independent prognostic factor. Decision curve analysis (DCA) indicated that FR risk score could increase the net benefit when making clinical-decision. In addition, we constructed a nomogram to predict the overall survival rate (OSR) of individual at 1,2,3 year. Meanwhile, the prognostic value was partly validated in ICGC cohort. Through immune analyses, we found that high FR risk could affect the immune abundances of five lymphocytes but not effectively affect the activities of immune-related pathways. The expressions of most FR risk genes did not correlate with that of PD-L1(CD274) and CTLA4. Further, through RT-qPCR tests, the expressions of PTGS2 and SQLE were proven to be significantly upregulated in normal pancreatic duct epithelia cell (HPDE6-C7) compared to pancreatic cancer cells (SW1990 and BxPC-3). MTT, wound-healing and transwell assays revealed that silencing PTGS2 and SQLE could inhibit the proliferation, migration and invasion of pancreatic cancer cells. Besides, western-blot assays showed that blocking PTGS2 and SQLE expressions could suppress the protein expressions of cyclin D1 and N-cadherin, but facilitate that of E-cadherin, which suggested that they were involved in the epithelial to mesenchymal transition (EMT). Collectively, FR risk signature provides an important complement for PAAD prognostic analysis. High FR risk level can adversely affect anti-tumor immune process, but may not serve as a predictive marker of ICIs efficacy. PTGS2 and SQLE are proven to possess cancer-promoting abilities in PAAD.
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| http://dx.doi.org/10.1016/j.gene.2021.145804 | DOI Listing |
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Bioinformatic mining and validation of the effects of ferroptosis regulators on the prognosis and progression of pancreatic adenocarcinoma.
Gene
August 2021
Department of Emergency, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710000, Shaanxi Province, China. Electronic address:
Article Synopsis
- - Ferroptosis is a type of programmed cell death that could be a promising strategy for treating pancreatic adenocarcinoma (PAAD), but the roles of ferroptosis-related genes in this context are not fully understood.
- - A study created a novel risk signature from six ferroptosis-related genes and determined that it could independently predict patient outcomes, showing potential for improving clinical decision-making.
- - Further analyses indicated that high ferroptosis risk levels impacted immune cell presence but did not significantly alter immune pathways, and specific gene silencing experiments showed that two genes, PTGS2 and SQLE, played a role in tumor cell behaviors and epithelial to mesenchymal transition.
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