Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB
ObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn thi...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253586/full |
| _version_ | 1827814849344700416 |
|---|---|
| author | Situ Xiong Situ Xiong Sheng Li Sheng Li Jin Zeng Jin Zeng Jianqiang Nie Jianqiang Nie Taobin Liu Taobin Liu Xiaoqiang Liu Luyao Chen Bin Fu Bin Fu Jun Deng Songhui Xu Songhui Xu |
| author_facet | Situ Xiong Situ Xiong Sheng Li Sheng Li Jin Zeng Jin Zeng Jianqiang Nie Jianqiang Nie Taobin Liu Taobin Liu Xiaoqiang Liu Luyao Chen Bin Fu Bin Fu Jun Deng Songhui Xu Songhui Xu |
| author_sort | Situ Xiong |
| collection | DOAJ |
| description | ObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn this study, we analyzed gene expression data and clinical information of 594 BLCA samples. We used unsupervised clustering to identify molecular subtypes based on the expression levels of PRR genes. Functional and pathway enrichment analyses were performed to understand the biological activities of these subtypes. We also assessed the TIME and developed a prognostic signature and scoring system. Moreover, we analyzed the efficacy of immune checkpoint inhibitors. Then we conducted real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments to detect the expression level of prolyl 4-hydroxylase subunit beta (P4HB) in BLCA cell lines. Transfection of small interference ribonucleic acid (siRNA) was performed in 5637 and EJ cells to knock down P4HB, and the impact of P4HB on cellular functions was evaluated through wound-healing and transwell assays. Finally, siRNA transfection of P4HB was performed in the cisplatin-resistant T24 cell to assess its impact on the sensitivity of BLCA to platinum-based chemotherapy drugs.ResultsIn a cohort of 594 BLCA samples (TCGA-BLCA, n=406; GSE13507, n=188), 846 PRR-associated genes were identified by intersecting BLCA expression data from TCGA and GEO databases with the PRR genes from the HGSOC-Platinum database. Univariate Cox regression analysis revealed 264 PRR genes linked to BLCA prognosis. We identified three molecular subtypes (Cluster A-C) and the PRR scoring system based on PRR genes. Cluster C exhibited a better prognosis and lower immune cell infiltration compared to the other Clusters A and B. The high PRR score group was significantly associated with an immunosuppressive tumor microenvironment, poor clinical-pathological features, and a poor prognosis. Furthermore, the high PRR group showed higher expression of immune checkpoint molecules and a poorer response to immune checkpoint inhibitors than the low PRR group. The key PRR gene P4HB was highly expressed in BLCA cell lines, and cellular functional experiments in vitro indicate that P4HB may be an important factor influencing BLCA migration and invasion.ConclusionOur study demonstrates that the PRR signatures are significantly associated with clinical-pathological features, the TIME, and prognostic features. The key PRR gene, P4HB, s a biomarker for the individualized treatment of BLCA patients. |
| first_indexed | 2024-03-11T23:51:43Z |
| format | Article |
| id | doaj.art-fbb6786823e44c899ab322e0ffadd503 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T23:51:43Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fbb6786823e44c899ab322e0ffadd5032023-09-19T07:25:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12535861253586Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HBSitu Xiong0Situ Xiong1Sheng Li2Sheng Li3Jin Zeng4Jin Zeng5Jianqiang Nie6Jianqiang Nie7Taobin Liu8Taobin Liu9Xiaoqiang Liu10Luyao Chen11Bin Fu12Bin Fu13Jun Deng14Songhui Xu15Songhui Xu16Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, ChinaJiangxi Institute of Urology, Nanchang, ChinaObjectivesTo identify the molecular subtypes and develop a scoring system for the tumor immune microenvironment (TIME) and prognostic features of bladder cancer (BLCA) based on the platinum-resistance-related (PRR) genes analysis while identifying P4HB as a potential therapeutic target.MethodsIn this study, we analyzed gene expression data and clinical information of 594 BLCA samples. We used unsupervised clustering to identify molecular subtypes based on the expression levels of PRR genes. Functional and pathway enrichment analyses were performed to understand the biological activities of these subtypes. We also assessed the TIME and developed a prognostic signature and scoring system. Moreover, we analyzed the efficacy of immune checkpoint inhibitors. Then we conducted real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) experiments to detect the expression level of prolyl 4-hydroxylase subunit beta (P4HB) in BLCA cell lines. Transfection of small interference ribonucleic acid (siRNA) was performed in 5637 and EJ cells to knock down P4HB, and the impact of P4HB on cellular functions was evaluated through wound-healing and transwell assays. Finally, siRNA transfection of P4HB was performed in the cisplatin-resistant T24 cell to assess its impact on the sensitivity of BLCA to platinum-based chemotherapy drugs.ResultsIn a cohort of 594 BLCA samples (TCGA-BLCA, n=406; GSE13507, n=188), 846 PRR-associated genes were identified by intersecting BLCA expression data from TCGA and GEO databases with the PRR genes from the HGSOC-Platinum database. Univariate Cox regression analysis revealed 264 PRR genes linked to BLCA prognosis. We identified three molecular subtypes (Cluster A-C) and the PRR scoring system based on PRR genes. Cluster C exhibited a better prognosis and lower immune cell infiltration compared to the other Clusters A and B. The high PRR score group was significantly associated with an immunosuppressive tumor microenvironment, poor clinical-pathological features, and a poor prognosis. Furthermore, the high PRR group showed higher expression of immune checkpoint molecules and a poorer response to immune checkpoint inhibitors than the low PRR group. The key PRR gene P4HB was highly expressed in BLCA cell lines, and cellular functional experiments in vitro indicate that P4HB may be an important factor influencing BLCA migration and invasion.ConclusionOur study demonstrates that the PRR signatures are significantly associated with clinical-pathological features, the TIME, and prognostic features. The key PRR gene, P4HB, s a biomarker for the individualized treatment of BLCA patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253586/fullplatinum resistancebladder cancermolecular subtypesimmune microenvironmentimmunotherapyprognosis |
| spellingShingle | Situ Xiong Situ Xiong Sheng Li Sheng Li Jin Zeng Jin Zeng Jianqiang Nie Jianqiang Nie Taobin Liu Taobin Liu Xiaoqiang Liu Luyao Chen Bin Fu Bin Fu Jun Deng Songhui Xu Songhui Xu Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB Frontiers in Immunology platinum resistance bladder cancer molecular subtypes immune microenvironment immunotherapy prognosis |
| title | Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB |
| title_full | Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB |
| title_fullStr | Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB |
| title_full_unstemmed | Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB |
| title_short | Deciphering the immunological and prognostic features of bladder cancer through platinum-resistance-related genes analysis and identifying potential therapeutic target P4HB |
| title_sort | deciphering the immunological and prognostic features of bladder cancer through platinum resistance related genes analysis and identifying potential therapeutic target p4hb |
| topic | platinum resistance bladder cancer molecular subtypes immune microenvironment immunotherapy prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1253586/full |
| work_keys_str_mv | AT situxiong decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT situxiong decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT shengli decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT shengli decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT jinzeng decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT jinzeng decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT jianqiangnie decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT jianqiangnie decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT taobinliu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT taobinliu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT xiaoqiangliu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT luyaochen decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT binfu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT binfu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT jundeng decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT songhuixu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb AT songhuixu decipheringtheimmunologicalandprognosticfeaturesofbladdercancerthroughplatinumresistancerelatedgenesanalysisandidentifyingpotentialtherapeutictargetp4hb |