Identification of cancer-associated fibroblasts subtypes in prostate cancer
IntroductionCancer-associated fibroblasts (CAFs) are one of the most abundant cell types in tumor microenvironment. However, the phenotypic and functional heterogeneities among CAFs have not been sufficiently investigated in prostate cancer.MethodsWe obtained and analyzed the single-cell RNA-sequenc...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1133160/full |
| _version_ | 1797861119723831296 |
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| author | Jiahua Pan Zehua Ma Bo Liu Hongyang Qian Xiaoguang Shao Jiazhou Liu Qi Wang Qi Wang Wei Xue |
| author_facet | Jiahua Pan Zehua Ma Bo Liu Hongyang Qian Xiaoguang Shao Jiazhou Liu Qi Wang Qi Wang Wei Xue |
| author_sort | Jiahua Pan |
| collection | DOAJ |
| description | IntroductionCancer-associated fibroblasts (CAFs) are one of the most abundant cell types in tumor microenvironment. However, the phenotypic and functional heterogeneities among CAFs have not been sufficiently investigated in prostate cancer.MethodsWe obtained and analyzed the single-cell RNA-sequencing data from 26 hormone-sensitive prostate cancer samples and 8 castration-resistant prostate cancer samples, along with the analysis of bulk-sequencing datasets. Furthermore, we performed multicolor immunofluorescence staining to verify the findings from the data analysis.ResultsWe identified two major CAFs subtypes with distinct molecular characteristics and biological functions in prostate cancer microenvironment, namely αSMA+ CAV1+ CAFs-C0 and FN1+ FAP+ CAFs-C1. Another single-cell RNA-sequencing dataset containing 7 bone metastatic prostate cancer samples demonstrated that osteoblasts in the bone metastatic lesions comprised two subtypes with molecular characteristics and biological functions similar to CAFs-C0 and CAFs-C1 in the primary tumor sites. In addition, we discovered a transcriptional factor regulatory network depending on CAFs-C1. CAFs-C1, but not CAFs-C0, was associated with castration resistance and poor prognosis. We also found that CAFs-C1 signature was involved in treatment resistance to immune checkpoint inhibitors.DiscussionIn summary, our results identified the presence of heterogeneous CAFs subtypes in prostate cancer microenvironment and the potential of specific CAFs subtype as therapeutic target for castration-resistant prostate cancer. |
| first_indexed | 2024-04-09T21:56:56Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T21:56:56Z |
| publishDate | 2023-03-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-f31523bcbbef4379b1cfcd665270cdb22023-03-24T04:58:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11331601133160Identification of cancer-associated fibroblasts subtypes in prostate cancerJiahua Pan0Zehua Ma1Bo Liu2Hongyang Qian3Xiaoguang Shao4Jiazhou Liu5Qi Wang6Qi Wang7Wei Xue8Department of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Key Laboratory for Tumor Microenvironment and Inflammation, School of Medicine, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Urology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaIntroductionCancer-associated fibroblasts (CAFs) are one of the most abundant cell types in tumor microenvironment. However, the phenotypic and functional heterogeneities among CAFs have not been sufficiently investigated in prostate cancer.MethodsWe obtained and analyzed the single-cell RNA-sequencing data from 26 hormone-sensitive prostate cancer samples and 8 castration-resistant prostate cancer samples, along with the analysis of bulk-sequencing datasets. Furthermore, we performed multicolor immunofluorescence staining to verify the findings from the data analysis.ResultsWe identified two major CAFs subtypes with distinct molecular characteristics and biological functions in prostate cancer microenvironment, namely αSMA+ CAV1+ CAFs-C0 and FN1+ FAP+ CAFs-C1. Another single-cell RNA-sequencing dataset containing 7 bone metastatic prostate cancer samples demonstrated that osteoblasts in the bone metastatic lesions comprised two subtypes with molecular characteristics and biological functions similar to CAFs-C0 and CAFs-C1 in the primary tumor sites. In addition, we discovered a transcriptional factor regulatory network depending on CAFs-C1. CAFs-C1, but not CAFs-C0, was associated with castration resistance and poor prognosis. We also found that CAFs-C1 signature was involved in treatment resistance to immune checkpoint inhibitors.DiscussionIn summary, our results identified the presence of heterogeneous CAFs subtypes in prostate cancer microenvironment and the potential of specific CAFs subtype as therapeutic target for castration-resistant prostate cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1133160/fullcancer-associated fibroblastsheterogeneitycastration resistanceprognosisprostate cancer |
| spellingShingle | Jiahua Pan Zehua Ma Bo Liu Hongyang Qian Xiaoguang Shao Jiazhou Liu Qi Wang Qi Wang Wei Xue Identification of cancer-associated fibroblasts subtypes in prostate cancer Frontiers in Immunology cancer-associated fibroblasts heterogeneity castration resistance prognosis prostate cancer |
| title | Identification of cancer-associated fibroblasts subtypes in prostate cancer |
| title_full | Identification of cancer-associated fibroblasts subtypes in prostate cancer |
| title_fullStr | Identification of cancer-associated fibroblasts subtypes in prostate cancer |
| title_full_unstemmed | Identification of cancer-associated fibroblasts subtypes in prostate cancer |
| title_short | Identification of cancer-associated fibroblasts subtypes in prostate cancer |
| title_sort | identification of cancer associated fibroblasts subtypes in prostate cancer |
| topic | cancer-associated fibroblasts heterogeneity castration resistance prognosis prostate cancer |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1133160/full |
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