Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer
BackgroundCancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment (TME). These cells play a supportive role throughout cancer progression. Their ability to modulate the immune system has also been noted. However, there has been limited investigation of CAFs in the...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.956224/full |
| _version_ | 1828324657512579072 |
|---|---|
| author | Ruoyao Zou Qidi Jiang Tianqiang Jin Mo Chen Liangqing Yao Hongda Ding |
| author_facet | Ruoyao Zou Qidi Jiang Tianqiang Jin Mo Chen Liangqing Yao Hongda Ding |
| author_sort | Ruoyao Zou |
| collection | DOAJ |
| description | BackgroundCancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment (TME). These cells play a supportive role throughout cancer progression. Their ability to modulate the immune system has also been noted. However, there has been limited investigation of CAFs in the TME of epithelial ovarian cancer (EOC).MethodsWe comprehensively evaluated the CAF landscape and its association with gene alterations, clinical features, prognostic value, and immune cell infiltration at the pan-cancer level using multi-omic data from The Cancer Genome Atlas (TCGA). The CAF contents were characterized by CAF scores based on the expression levels of seven CAF markers using the R package “GSVA.” Next, we identified the molecular subtypes defined by CAF markers and constructed a CAF riskscore system using principal component analysis in the EOC cohort. The correlation between CAF riskscore and TME cell infiltration was investigated. The ability of the CAF riskscore to predict prognosis and immunotherapy response was also examined.ResultsCAF components were involved in multiple immune-related processes, including transforming growth factor (TGF)-β signaling, IL2-STAT signaling, inflammatory responses, and Interleukin (IL) 2-signal transducer and activator of transcription (STAT) signaling. Considering the positive correlation between CAF scores and macrophages, neutrophils, and mast cells, CAFs may exert immunosuppressive effects in both pan-cancer and ovarian cancer cohorts, which may explain accelerated tumor progression and poor outcomes. Notably, two distinct CAF molecular subtypes were defined in the EOC cohort. Low CAF riskscores were characterized by favorable overall survival (OS) and higher efficacy of immunotherapy. Furthermore, 24 key genes were identified in CAF subtypes. These genes were significantly upregulated in EOC and showed a strong correlation with CAF markers.ConclusionsIdentifying CAF subtypes provides insights into EOC heterogeneity. The CAF riskscore system can predict prognosis and select patients who may benefit from immunotherapy. The mechanism of interactions between key genes, CAF markers, and associated cancer-promoting effects needs to be further elucidated. |
| first_indexed | 2024-04-13T19:08:52Z |
| format | Article |
| id | doaj.art-24873801dccc49d4ae92f430325d93fe |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T19:08:52Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-24873801dccc49d4ae92f430325d93fe2022-12-22T02:33:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-08-011310.3389/fimmu.2022.956224956224Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancerRuoyao Zou0Qidi Jiang1Tianqiang Jin2Mo Chen3Liangqing Yao4Hongda Ding5Department of Gynecologic Oncology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaDepartment of General Surgery, ShengJing Hospital of China Medical University, Shenyang, ChinaDepartment of Gynecologic Oncology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaDepartment of General Surgery, ShengJing Hospital of China Medical University, Shenyang, ChinaBackgroundCancer-associated fibroblasts (CAFs) are essential components of the tumor microenvironment (TME). These cells play a supportive role throughout cancer progression. Their ability to modulate the immune system has also been noted. However, there has been limited investigation of CAFs in the TME of epithelial ovarian cancer (EOC).MethodsWe comprehensively evaluated the CAF landscape and its association with gene alterations, clinical features, prognostic value, and immune cell infiltration at the pan-cancer level using multi-omic data from The Cancer Genome Atlas (TCGA). The CAF contents were characterized by CAF scores based on the expression levels of seven CAF markers using the R package “GSVA.” Next, we identified the molecular subtypes defined by CAF markers and constructed a CAF riskscore system using principal component analysis in the EOC cohort. The correlation between CAF riskscore and TME cell infiltration was investigated. The ability of the CAF riskscore to predict prognosis and immunotherapy response was also examined.ResultsCAF components were involved in multiple immune-related processes, including transforming growth factor (TGF)-β signaling, IL2-STAT signaling, inflammatory responses, and Interleukin (IL) 2-signal transducer and activator of transcription (STAT) signaling. Considering the positive correlation between CAF scores and macrophages, neutrophils, and mast cells, CAFs may exert immunosuppressive effects in both pan-cancer and ovarian cancer cohorts, which may explain accelerated tumor progression and poor outcomes. Notably, two distinct CAF molecular subtypes were defined in the EOC cohort. Low CAF riskscores were characterized by favorable overall survival (OS) and higher efficacy of immunotherapy. Furthermore, 24 key genes were identified in CAF subtypes. These genes were significantly upregulated in EOC and showed a strong correlation with CAF markers.ConclusionsIdentifying CAF subtypes provides insights into EOC heterogeneity. The CAF riskscore system can predict prognosis and select patients who may benefit from immunotherapy. The mechanism of interactions between key genes, CAF markers, and associated cancer-promoting effects needs to be further elucidated.https://www.frontiersin.org/articles/10.3389/fimmu.2022.956224/fullcancer-associated fibroblastepithelial ovarian cancertumor microenvironmentprognosisimmunotherapy |
| spellingShingle | Ruoyao Zou Qidi Jiang Tianqiang Jin Mo Chen Liangqing Yao Hongda Ding Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer Frontiers in Immunology cancer-associated fibroblast epithelial ovarian cancer tumor microenvironment prognosis immunotherapy |
| title | Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer |
| title_full | Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer |
| title_fullStr | Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer |
| title_full_unstemmed | Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer |
| title_short | Pan-cancer analyses and molecular subtypes based on the cancer-associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer |
| title_sort | pan cancer analyses and molecular subtypes based on the cancer associated fibroblast landscape and tumor microenvironment infiltration characterization reveal clinical outcome and immunotherapy response in epithelial ovarian cancer |
| topic | cancer-associated fibroblast epithelial ovarian cancer tumor microenvironment prognosis immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.956224/full |
| work_keys_str_mv | AT ruoyaozou pancanceranalysesandmolecularsubtypesbasedonthecancerassociatedfibroblastlandscapeandtumormicroenvironmentinfiltrationcharacterizationrevealclinicaloutcomeandimmunotherapyresponseinepithelialovariancancer AT qidijiang pancanceranalysesandmolecularsubtypesbasedonthecancerassociatedfibroblastlandscapeandtumormicroenvironmentinfiltrationcharacterizationrevealclinicaloutcomeandimmunotherapyresponseinepithelialovariancancer AT tianqiangjin pancanceranalysesandmolecularsubtypesbasedonthecancerassociatedfibroblastlandscapeandtumormicroenvironmentinfiltrationcharacterizationrevealclinicaloutcomeandimmunotherapyresponseinepithelialovariancancer AT mochen pancanceranalysesandmolecularsubtypesbasedonthecancerassociatedfibroblastlandscapeandtumormicroenvironmentinfiltrationcharacterizationrevealclinicaloutcomeandimmunotherapyresponseinepithelialovariancancer AT liangqingyao pancanceranalysesandmolecularsubtypesbasedonthecancerassociatedfibroblastlandscapeandtumormicroenvironmentinfiltrationcharacterizationrevealclinicaloutcomeandimmunotherapyresponseinepithelialovariancancer AT hongdading pancanceranalysesandmolecularsubtypesbasedonthecancerassociatedfibroblastlandscapeandtumormicroenvironmentinfiltrationcharacterizationrevealclinicaloutcomeandimmunotherapyresponseinepithelialovariancancer |