A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer
Pancreatic cancer is one of the most lethal tumors owing to its unspecific symptoms during the early stage and multiple treatment resistances. Pyroptosis, a newly discovered gasdermin-mediated cell death, facilitates anti- or pro-tumor effects in a variety of cancers, whereas the impact of pyroptosi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.817919/full |
| _version_ | 1811185703950745600 |
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| author | Sifan Tao Sifan Tao Li Tian Xiaoyan Wang Yajun Shou Yajun Shou |
| author_facet | Sifan Tao Sifan Tao Li Tian Xiaoyan Wang Yajun Shou Yajun Shou |
| author_sort | Sifan Tao |
| collection | DOAJ |
| description | Pancreatic cancer is one of the most lethal tumors owing to its unspecific symptoms during the early stage and multiple treatment resistances. Pyroptosis, a newly discovered gasdermin-mediated cell death, facilitates anti- or pro-tumor effects in a variety of cancers, whereas the impact of pyroptosis in pancreatic cancer remains unclear. Therefore, we downloaded RNA expression and clinic data from the TCGA-PAAD cohort and were surprised to find that most pyroptosis-related genes (PRGs) are not only overexpressed in tumor tissue but also strongly associated with overall survival. For their remarkable prognostic value, cox regression analysis and lasso regression were used to establish a five-gene signature. All patients were divided into low- and high-risk groups based on the media value of the risk score, and we discovered that low-risk patients had better outcomes in both the testing and validation cohorts using time receiver operating characteristic (ROC), nomograms, survival, and decision analysis. More importantly, a higher somatic mutation burden and less immune cell infiltration were found in the high-risk group. Following that, we predicted tumor response to chemotherapy and immunotherapy in both low- and high-risk groups, which suggests patients with low risk were more likely to respond to both immunotherapy and chemotherapy. To summarize, our study established an effective model that can help clinicians better predict patients’ drug responses and outcomes, and we also present basic evidence for future pyroptosis related studies in pancreatic cancer. |
| first_indexed | 2024-04-11T13:33:42Z |
| format | Article |
| id | doaj.art-df2412242f454909a46218f05798d13d |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T13:33:42Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-df2412242f454909a46218f05798d13d2022-12-22T04:21:42ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-08-011310.3389/fgene.2022.817919817919A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancerSifan Tao0Sifan Tao1Li Tian2Xiaoyan Wang3Yajun Shou4Yajun Shou5Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaResearch Center of Digestive Disease, Central South University, Changsha, Hunan, ChinaPancreatic cancer is one of the most lethal tumors owing to its unspecific symptoms during the early stage and multiple treatment resistances. Pyroptosis, a newly discovered gasdermin-mediated cell death, facilitates anti- or pro-tumor effects in a variety of cancers, whereas the impact of pyroptosis in pancreatic cancer remains unclear. Therefore, we downloaded RNA expression and clinic data from the TCGA-PAAD cohort and were surprised to find that most pyroptosis-related genes (PRGs) are not only overexpressed in tumor tissue but also strongly associated with overall survival. For their remarkable prognostic value, cox regression analysis and lasso regression were used to establish a five-gene signature. All patients were divided into low- and high-risk groups based on the media value of the risk score, and we discovered that low-risk patients had better outcomes in both the testing and validation cohorts using time receiver operating characteristic (ROC), nomograms, survival, and decision analysis. More importantly, a higher somatic mutation burden and less immune cell infiltration were found in the high-risk group. Following that, we predicted tumor response to chemotherapy and immunotherapy in both low- and high-risk groups, which suggests patients with low risk were more likely to respond to both immunotherapy and chemotherapy. To summarize, our study established an effective model that can help clinicians better predict patients’ drug responses and outcomes, and we also present basic evidence for future pyroptosis related studies in pancreatic cancer.https://www.frontiersin.org/articles/10.3389/fgene.2022.817919/fullpyroptosispancreatic cancerimmune microenvironmentprognostic modeltherapeutic response prediction |
| spellingShingle | Sifan Tao Sifan Tao Li Tian Xiaoyan Wang Yajun Shou Yajun Shou A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer Frontiers in Genetics pyroptosis pancreatic cancer immune microenvironment prognostic model therapeutic response prediction |
| title | A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer |
| title_full | A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer |
| title_fullStr | A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer |
| title_full_unstemmed | A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer |
| title_short | A pyroptosis-related gene signature for prognosis and immune microenvironment of pancreatic cancer |
| title_sort | pyroptosis related gene signature for prognosis and immune microenvironment of pancreatic cancer |
| topic | pyroptosis pancreatic cancer immune microenvironment prognostic model therapeutic response prediction |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.817919/full |
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