Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer
Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC.Methods: Th...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1054152/full |
| _version_ | 1811186647243423744 |
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| author | Lei Zhang Chao Xu Si-Han Wang Qin-Wen Ge Xiao-Wei Wang Pan Xiao Qing-Hua Yao Qing-Hua Yao Qing-Hua Yao |
| author_facet | Lei Zhang Chao Xu Si-Han Wang Qin-Wen Ge Xiao-Wei Wang Pan Xiao Qing-Hua Yao Qing-Hua Yao Qing-Hua Yao |
| author_sort | Lei Zhang |
| collection | DOAJ |
| description | Background: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC.Methods: The clinical information and corresponding RNA data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Estimation of STromal and Immune cells in MAlignant Tumor tissues (ESTIMATES) and xCell methods were applied to evaluate the tumor microenvironment infiltration from bulk gene expression data. Weighted gene co-expression network analysis (WGCNA) was used to construct co-expression modules. The key module was identified by calculating the module-trait correlations. The univariate Cox regression and least absolute shrinkage operator (LASSO) analyses were combined to develop a CAFs-related signature for the prognostic model. Moreover, pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to predict chemosensitivity and immunotherapy response. Human Protein Atlas (HPA) databases were employed to evaluate the protein expressions.Results: ESTIMATES and xCell analysis showed that high CAFs infiltration was associated with adverse prognoses. A twenty-gene CAFs-related prognostic signature (CAFPS) was established in the training cohort. Kaplan-Meier survival analyses reveled that CRC patients with higher CAFs risk scores were associated with poor prognosis in each cohort. Univariate and multivariate Cox regression analyses verified that CAFPS was as an independent prognostic factor in predicting overall survival, and a nomogram was built for clinical utility in predicting CRC prognosis. Patients with higher CAFs risk scores tended to not respond to immunotherapy, but were more sensitive to five conventional chemotherapeutic drugs.Conclusion: In summary, the CAFPS could serve as a robust prognostic indicator in CRC patients, which might help to optimize risk stratification and provide a new insight into individual treatments for CRC. |
| first_indexed | 2024-04-11T13:48:53Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-11T13:48:53Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-dbfa38eecedc45d48cad6814cbad66572022-12-22T04:20:50ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.10541521054152Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancerLei Zhang0Chao Xu1Si-Han Wang2Qin-Wen Ge3Xiao-Wei Wang4Pan Xiao5Qing-Hua Yao6Qing-Hua Yao7Qing-Hua Yao8Department of Integrated Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaDepartment of Integrated Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaThe Second College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First College of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Plastic Surgery, Zhejiang Hospital, Hangzhou, ChinaDepartment of Integrated Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaDepartment of Integrated Chinese and Western Medicine, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaIntegrated Traditional Chinese and Western Medicine Oncology Laboratory, Key Laboratory of Traditional Chinese Medicine of Zhejiang Province, Hangzhou, ChinaKey Laboratory of Head and Neck Cancer Translational Research of Zhejiang Province, Hangzhou, ChinaBackground: Cancer-associated fibroblasts (CAFs) play an important role in the tumorigenesis, immunosuppression and metastasis of colorectal cancer (CRC), and can predict poor prognosis in patients with CRC. The present study aimed to construct a CAFs-related prognostic signature for CRC.Methods: The clinical information and corresponding RNA data of CRC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Estimation of STromal and Immune cells in MAlignant Tumor tissues (ESTIMATES) and xCell methods were applied to evaluate the tumor microenvironment infiltration from bulk gene expression data. Weighted gene co-expression network analysis (WGCNA) was used to construct co-expression modules. The key module was identified by calculating the module-trait correlations. The univariate Cox regression and least absolute shrinkage operator (LASSO) analyses were combined to develop a CAFs-related signature for the prognostic model. Moreover, pRRophetic and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms were utilized to predict chemosensitivity and immunotherapy response. Human Protein Atlas (HPA) databases were employed to evaluate the protein expressions.Results: ESTIMATES and xCell analysis showed that high CAFs infiltration was associated with adverse prognoses. A twenty-gene CAFs-related prognostic signature (CAFPS) was established in the training cohort. Kaplan-Meier survival analyses reveled that CRC patients with higher CAFs risk scores were associated with poor prognosis in each cohort. Univariate and multivariate Cox regression analyses verified that CAFPS was as an independent prognostic factor in predicting overall survival, and a nomogram was built for clinical utility in predicting CRC prognosis. Patients with higher CAFs risk scores tended to not respond to immunotherapy, but were more sensitive to five conventional chemotherapeutic drugs.Conclusion: In summary, the CAFPS could serve as a robust prognostic indicator in CRC patients, which might help to optimize risk stratification and provide a new insight into individual treatments for CRC.https://www.frontiersin.org/articles/10.3389/fgene.2022.1054152/fullcolorectal cancercancer-associated fibroblaststumor microenvironmentprognosisWGCNA |
| spellingShingle | Lei Zhang Chao Xu Si-Han Wang Qin-Wen Ge Xiao-Wei Wang Pan Xiao Qing-Hua Yao Qing-Hua Yao Qing-Hua Yao Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer Frontiers in Genetics colorectal cancer cancer-associated fibroblasts tumor microenvironment prognosis WGCNA |
| title | Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer |
| title_full | Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer |
| title_fullStr | Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer |
| title_full_unstemmed | Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer |
| title_short | Cancer-associated fibroblast-related gene signatures predict survival and drug response in patients with colorectal cancer |
| title_sort | cancer associated fibroblast related gene signatures predict survival and drug response in patients with colorectal cancer |
| topic | colorectal cancer cancer-associated fibroblasts tumor microenvironment prognosis WGCNA |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1054152/full |
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