Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients
Abstract Background Cancer-associated fibroblasts (CAFs) play multiple roles in regulating tumor metastasis and treatment response. Current clinical indicators are insufficient to accurately assess disease risk and radiotherapy response, emphasizing the urgent need for additional molecular prognosti...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-022-03656-5 |
| _version_ | 1797996172776833024 |
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| author | Ran Zhang Feng Liu |
| author_facet | Ran Zhang Feng Liu |
| author_sort | Ran Zhang |
| collection | DOAJ |
| description | Abstract Background Cancer-associated fibroblasts (CAFs) play multiple roles in regulating tumor metastasis and treatment response. Current clinical indicators are insufficient to accurately assess disease risk and radiotherapy response, emphasizing the urgent need for additional molecular prognostic markers. Methods In order to investigate CAF-related genes associated with radiotherapy and construct prognostic CAF-related gene signatures for prostate cancer, we firstly established a radio-resistant prostate CAF cell subline (referred to as CAFR) from Mus-CAF (referred to as CAF) through fractionated irradiation using X-rays. Transcriptome sequencing for CAF and CAFR was conducted, and 2626 CAF-related differentially expressed genes (DEGs) associated with radiotherapy were identified. Human homologous genes of mouse CAF-related DEGs were then obtained. Results Functional enrichment analysis revealed that these CAF-related DEGs were significantly enriched ECM- and immune-related functions and pathways. Based on GSE116918 dataset, 186 CAF-related DEGs were correlated with biochemical recurrence-free survival (BCRFS) of prostate cancer patients, 16 of which were selected to construct a BCRFS-related CAF signature, such as ACPP, THBS2, and KCTD14; 142 CAF-related DEGs were correlated with metastasis-free survival (MFS), 16 of which were used to construct a MFS-related CAF signature, such as HOPX, TMEM132A, and ZNF467. Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients. The risk scores were higher in patients with higher gleason grades and higher clinical T stages. Moreover, the BCRFS-related CAF signature was an independent prognostic factor and a nomogram consisting of BCRFS-related CAF signature and various clinical factors accurately predicted 2-, 3-, and 5-year survival time of prostate cancer patients. Furthermore, the risk score was positively correlated with multiple immune checkpoints. Conclusions Our established CAF signatures could accurately predict BCRFS and MFS in prostate cancer patients undergoing radiotherapy. |
| first_indexed | 2024-04-11T10:13:15Z |
| format | Article |
| id | doaj.art-ceafab5492904567ab8781dfdcdd257e |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-04-11T10:13:15Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-ceafab5492904567ab8781dfdcdd257e2022-12-22T04:30:03ZengBMCJournal of Translational Medicine1479-58762022-10-0120111810.1186/s12967-022-03656-5Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patientsRan Zhang0Feng Liu1Laboratory of Radio-Immunology, Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical SciencesDepartment of Immunology, School of Biomedical Sciences, Shandong UniversityAbstract Background Cancer-associated fibroblasts (CAFs) play multiple roles in regulating tumor metastasis and treatment response. Current clinical indicators are insufficient to accurately assess disease risk and radiotherapy response, emphasizing the urgent need for additional molecular prognostic markers. Methods In order to investigate CAF-related genes associated with radiotherapy and construct prognostic CAF-related gene signatures for prostate cancer, we firstly established a radio-resistant prostate CAF cell subline (referred to as CAFR) from Mus-CAF (referred to as CAF) through fractionated irradiation using X-rays. Transcriptome sequencing for CAF and CAFR was conducted, and 2626 CAF-related differentially expressed genes (DEGs) associated with radiotherapy were identified. Human homologous genes of mouse CAF-related DEGs were then obtained. Results Functional enrichment analysis revealed that these CAF-related DEGs were significantly enriched ECM- and immune-related functions and pathways. Based on GSE116918 dataset, 186 CAF-related DEGs were correlated with biochemical recurrence-free survival (BCRFS) of prostate cancer patients, 16 of which were selected to construct a BCRFS-related CAF signature, such as ACPP, THBS2, and KCTD14; 142 CAF-related DEGs were correlated with metastasis-free survival (MFS), 16 of which were used to construct a MFS-related CAF signature, such as HOPX, TMEM132A, and ZNF467. Both Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets confirmed that the two CAF signatures accurately predicted BCRFS and MFS of prostate cancer patients. The risk scores were higher in patients with higher gleason grades and higher clinical T stages. Moreover, the BCRFS-related CAF signature was an independent prognostic factor and a nomogram consisting of BCRFS-related CAF signature and various clinical factors accurately predicted 2-, 3-, and 5-year survival time of prostate cancer patients. Furthermore, the risk score was positively correlated with multiple immune checkpoints. Conclusions Our established CAF signatures could accurately predict BCRFS and MFS in prostate cancer patients undergoing radiotherapy.https://doi.org/10.1186/s12967-022-03656-5Prostate cancerRadiotherapy prognosisCancer-associated fibroblastsGene signatureBiochemical recurrence-free survivalMetastasis-free survival |
| spellingShingle | Ran Zhang Feng Liu Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients Journal of Translational Medicine Prostate cancer Radiotherapy prognosis Cancer-associated fibroblasts Gene signature Biochemical recurrence-free survival Metastasis-free survival |
| title | Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients |
| title_full | Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients |
| title_fullStr | Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients |
| title_full_unstemmed | Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients |
| title_short | Cancer-associated fibroblast-derived gene signatures predict radiotherapeutic survival in prostate cancer patients |
| title_sort | cancer associated fibroblast derived gene signatures predict radiotherapeutic survival in prostate cancer patients |
| topic | Prostate cancer Radiotherapy prognosis Cancer-associated fibroblasts Gene signature Biochemical recurrence-free survival Metastasis-free survival |
| url | https://doi.org/10.1186/s12967-022-03656-5 |
| work_keys_str_mv | AT ranzhang cancerassociatedfibroblastderivedgenesignaturespredictradiotherapeuticsurvivalinprostatecancerpatients AT fengliu cancerassociatedfibroblastderivedgenesignaturespredictradiotherapeuticsurvivalinprostatecancerpatients |