Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients
Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023107031 |
| _version_ | 1797337024270696448 |
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| author | Dechao Feng Zhouting Tuo Jie Wang Luxia Ye Dengxiong Li Ruicheng Wu Wuran Wei Yubo Yang Chi Zhang |
| author_facet | Dechao Feng Zhouting Tuo Jie Wang Luxia Ye Dengxiong Li Ruicheng Wu Wuran Wei Yubo Yang Chi Zhang |
| author_sort | Dechao Feng |
| collection | DOAJ |
| description | Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines. |
| first_indexed | 2024-03-08T09:03:24Z |
| format | Article |
| id | doaj.art-562596ff1f344c9b8e2562544ec17c0d |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T09:03:24Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-562596ff1f344c9b8e2562544ec17c0d2024-02-01T06:32:07ZengElsevierHeliyon2405-84402024-01-01101e23495Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patientsDechao Feng0Zhouting Tuo1Jie Wang2Luxia Ye3Dengxiong Li4Ruicheng Wu5Wuran Wei6Yubo Yang7Chi Zhang8Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China; Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Corresponding author. Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, ChinaDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Public Research Platform, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, ChinaDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, ChinaDepartment of Urology, Three Gorges Hospital, Chongqing University, Wanzhou, Chongqing, 404000, China; Corresponding author. Department of Urology, Three Gorges Hospital, Chongqing University, Wanzhou, Chongqing, 404000, China.Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Corresponding author. Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.Background: We aimed to identify two new prognostic subtypes and create a predictive index for prostate cancer (PCa) patients based on ferroptosis database. Methods: The nonnegative matrix factorization approach was used to identify molecular subtypes. We investigate the differences between cluster 1 and cluster 2 in terms of clinical features, functional pathways, tumour stemness, tumour heterogeneity, gene mutation and tumour immune microenvironment score after identifying the two molecular subtypes. Colony formation assay and flow cytometry assay were performed. Results: The stratification of two clusters was closely connected to BCR-free survival using the nonnegative matrix factorization method, which was validated in the other three datasets. Furthermore, multivariate Cox regression analysis revealed that this classification was an independent risk factor for patients with PCa. Ribosome, aminoacyl tRNA production, oxidative phosphorylation, and Parkinson's disease-related pathways were shown to be highly enriched in cluster 1. In comparison to cluster 2, patients in cluster 1 exhibited significantly reduced CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells and tumor immune microenvironment scores. Only HHLA2 was more abundant in cluster 1. Moreover, we found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of C4-2B and DU145 cell lines. Conclusions: We discovered two new prognostic subtypes associated with immunological dysfunction in PCa patients based on ferroptosis-related genes and found that P4HB downregulation could significantly inhibit the colony formation ability and contributed to cell apoptosis of PCa cell lines.http://www.sciencedirect.com/science/article/pii/S2405844023107031Prostate cancerBiochemical recurrenceFerroptosisRadical prostatectomyNonnegative matrix factorizationMolecular subtypes |
| spellingShingle | Dechao Feng Zhouting Tuo Jie Wang Luxia Ye Dengxiong Li Ruicheng Wu Wuran Wei Yubo Yang Chi Zhang Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients Heliyon Prostate cancer Biochemical recurrence Ferroptosis Radical prostatectomy Nonnegative matrix factorization Molecular subtypes |
| title | Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients |
| title_full | Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients |
| title_fullStr | Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients |
| title_full_unstemmed | Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients |
| title_short | Establishment of novel ferroptosis-related prognostic subtypes correlating with immune dysfunction in prostate cancer patients |
| title_sort | establishment of novel ferroptosis related prognostic subtypes correlating with immune dysfunction in prostate cancer patients |
| topic | Prostate cancer Biochemical recurrence Ferroptosis Radical prostatectomy Nonnegative matrix factorization Molecular subtypes |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023107031 |
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