Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer
Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.951582/full |
| _version_ | 1818114793078259712 |
|---|---|
| author | Songwei Feng Yi Xu Zhu Dai Han Yin Ke Zhang Yang Shen |
| author_facet | Songwei Feng Yi Xu Zhu Dai Han Yin Ke Zhang Yang Shen |
| author_sort | Songwei Feng |
| collection | DOAJ |
| description | Cancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression. |
| first_indexed | 2024-12-11T03:56:22Z |
| format | Article |
| id | doaj.art-e56f6a71c60d4c8ebd3a52bf1fbc8df7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T03:56:22Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e56f6a71c60d4c8ebd3a52bf1fbc8df72022-12-22T01:21:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.951582951582Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian CancerSongwei Feng0Yi Xu1Zhu Dai2Han Yin3Ke Zhang4Yang Shen5Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, ChinaState Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, ChinaDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, ChinaDepartment of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, ChinaCancer-associated fibroblasts (CAFs) are a major contributor to tumor stromal crosstalk in the tumor microenvironment (TME) and boost tumor progression by promoting angiogenesis and lymphangiogenesis. This study aimed to identify prognostic genes associated with CAFs that lead to high morbidity and mortality in ovarian cancer (OC) patients. We performed bioinformatics analysis in 16 multicenter studies (2,742 patients) and identified CAF-associated hub genes using the weighted gene co-expression network analysis (WGCNA). A machine learning methodology was used to identify COL16A1, COL5A2, GREM1, LUM, SRPX, and TIMP3 and construct a prognostic signature. Subsequently, a series of bioinformatics algorithms indicated risk stratification based on the above signature, suggesting that high-risk patients have a worse prognosis, weaker immune response, and lower tumor mutational burden (TMB) status but may be more sensitive to routine chemotherapeutic agents. Finally, we characterized prognostic markers using cell lines, immunohistochemistry, and single-cell sequencing. In conclusion, these results suggest that the CAF-related signature may be a novel pretreatment guide for anti-CAFs, and prognostic markers in CAFs may be potential therapeutic targets to inhibit OC progression.https://www.frontiersin.org/articles/10.3389/fimmu.2022.951582/fullcancer-associated fibroblastsWGCNAovarian cancerprognosistumor microenvironment |
| spellingShingle | Songwei Feng Yi Xu Zhu Dai Han Yin Ke Zhang Yang Shen Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer Frontiers in Immunology cancer-associated fibroblasts WGCNA ovarian cancer prognosis tumor microenvironment |
| title | Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer |
| title_full | Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer |
| title_fullStr | Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer |
| title_full_unstemmed | Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer |
| title_short | Integrative Analysis From Multicenter Studies Identifies a WGCNA-Derived Cancer-Associated Fibroblast Signature for Ovarian Cancer |
| title_sort | integrative analysis from multicenter studies identifies a wgcna derived cancer associated fibroblast signature for ovarian cancer |
| topic | cancer-associated fibroblasts WGCNA ovarian cancer prognosis tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.951582/full |
| work_keys_str_mv | AT songweifeng integrativeanalysisfrommulticenterstudiesidentifiesawgcnaderivedcancerassociatedfibroblastsignatureforovariancancer AT yixu integrativeanalysisfrommulticenterstudiesidentifiesawgcnaderivedcancerassociatedfibroblastsignatureforovariancancer AT zhudai integrativeanalysisfrommulticenterstudiesidentifiesawgcnaderivedcancerassociatedfibroblastsignatureforovariancancer AT hanyin integrativeanalysisfrommulticenterstudiesidentifiesawgcnaderivedcancerassociatedfibroblastsignatureforovariancancer AT kezhang integrativeanalysisfrommulticenterstudiesidentifiesawgcnaderivedcancerassociatedfibroblastsignatureforovariancancer AT yangshen integrativeanalysisfrommulticenterstudiesidentifiesawgcnaderivedcancerassociatedfibroblastsignatureforovariancancer |