A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics
Background The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyropto...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PeerJ Inc.
2023-12-01
|
| Series: | PeerJ |
| Subjects: | |
| Online Access: | https://peerj.com/articles/16631.pdf |
| _version_ | 1797383194522157056 |
|---|---|
| author | Peicheng Jiang Jin Fan Shenglin Huang Luying Liu Minghua Bai Quanquan Sun Jinwen Shen Na Zhang Dong Liu Ning Zhou Yanru Feng Jin Jiang Ji Zhu |
| author_facet | Peicheng Jiang Jin Fan Shenglin Huang Luying Liu Minghua Bai Quanquan Sun Jinwen Shen Na Zhang Dong Liu Ning Zhou Yanru Feng Jin Jiang Ji Zhu |
| author_sort | Peicheng Jiang |
| collection | DOAJ |
| description | Background The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC. |
| first_indexed | 2024-03-08T21:17:02Z |
| format | Article |
| id | doaj.art-29d4747e483e4e598c21c19e67eed43d |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-08T21:17:02Z |
| publishDate | 2023-12-01 |
| publisher | PeerJ Inc. |
| record_format | Article |
| series | PeerJ |
| spelling | doaj.art-29d4747e483e4e598c21c19e67eed43d2023-12-21T15:05:22ZengPeerJ Inc.PeerJ2167-83592023-12-0111e1663110.7717/peerj.16631A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristicsPeicheng Jiang0Jin Fan1Shenglin Huang2Luying Liu3Minghua Bai4Quanquan Sun5Jinwen Shen6Na Zhang7Dong Liu8Ning Zhou9Yanru Feng10Jin Jiang11Ji Zhu12Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaFudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University, Shanghai, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaDepartment of Radiation Oncology, The First Hospital of Jiaxing Affiliated to Jiaxing University, Jiaxing, ChinaDepartment of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, ChinaBackground The heterogeneity of colorectal cancer (CRC) is the main cause of the disparity of drug sensitivity and the variability of prognosis. Pyroptosis is closely associated with the development and prognosis of various tumors, including CRC. Dividing CRC into distinct subgroups based on pyroptosis is a worthwhile topic for improving the precision treatment and prognosis prediction of CRC. Methods We classified patients into two clusters using the consensus clustering based on the pyroptosis-related genes (PRGs). Next, the prognostic signature was developed with LASSO regression analysis using the screened genes from differentially expressed genes (DEGs) by univariate and multivariate Cox analyses. According to the pyroptosis-related score (PR score) calculated with the signature, patients belonged to two groups with distinct prognosis. Moreover, we assessed the immune profile to explore the relationship between the signature and immunological characteristics. Two single cell sequencing databases were adopted for further exploration of tumor immune microenvironment (TME). In addition, we applied our own cohort and Drugbank to explore the correlation of the signature and clinical therapies. We also studied the expression of key genes by immunohistochemistry. Results The signature performed well in predicting the prognosis of CRC as the high area under curve (AUC) value demonstrated. Patients with a higher PR score had poorer prognosis and higher expression of immune checkpoints but more abundant infiltration of immune cells. Combining with the indicator of therapeutic analysis, they might benefit more from immune checkpoint blockade (ICB) and neo-adjuvant chemoradiotherapy (nCRT). Conclusion In conclusion, our study is based on genomics and transcriptomics to investigate the role of PRGs in CRC. We have established a prognostic signature and integrated single-cell data to study the relationship between the signature with the TME in CRC. Its clinical application in reliable prediction of prognosis and personalized treatment was validated by public and own sequencing cohort. It provided a new insight for the personalized treatment of CRC.https://peerj.com/articles/16631.pdfPyroptosisColorectal cancerPrognosisImmunological characteristicspersonalized treatment |
| spellingShingle | Peicheng Jiang Jin Fan Shenglin Huang Luying Liu Minghua Bai Quanquan Sun Jinwen Shen Na Zhang Dong Liu Ning Zhou Yanru Feng Jin Jiang Ji Zhu A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics PeerJ Pyroptosis Colorectal cancer Prognosis Immunological characteristics personalized treatment |
| title | A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics |
| title_full | A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics |
| title_fullStr | A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics |
| title_full_unstemmed | A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics |
| title_short | A pyroptosis-related signature in colorectal cancer: exploring its prognostic value and immunological characteristics |
| title_sort | pyroptosis related signature in colorectal cancer exploring its prognostic value and immunological characteristics |
| topic | Pyroptosis Colorectal cancer Prognosis Immunological characteristics personalized treatment |
| url | https://peerj.com/articles/16631.pdf |
| work_keys_str_mv | AT peichengjiang apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jinfan apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT shenglinhuang apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT luyingliu apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT minghuabai apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT quanquansun apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jinwenshen apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT nazhang apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT dongliu apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT ningzhou apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT yanrufeng apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jinjiang apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jizhu apyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT peichengjiang pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jinfan pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT shenglinhuang pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT luyingliu pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT minghuabai pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT quanquansun pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jinwenshen pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT nazhang pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT dongliu pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT ningzhou pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT yanrufeng pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jinjiang pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics AT jizhu pyroptosisrelatedsignatureincolorectalcancerexploringitsprognosticvalueandimmunologicalcharacteristics |