Identification of senescence-related molecular subtypes and key genes for prostate cancer

We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-relat...

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Main Authors: De-Chao Feng, Wei-Zhen Zhu, Xu Shi, Qiao Xiong, Jia You, Qiang Wei, Lu Yang
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2023-01-01
Series:Asian Journal of Andrology
Subjects:
Online Access:http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=2;spage=223;epage=229;aulast=Feng
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author De-Chao Feng
Wei-Zhen Zhu
Xu Shi
Qiao Xiong
Jia You
Qiang Wei
Lu Yang
author_facet De-Chao Feng
Wei-Zhen Zhu
Xu Shi
Qiao Xiong
Jia You
Qiang Wei
Lu Yang
author_sort De-Chao Feng
collection DOAJ
description We identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.
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spelling doaj.art-376ef2e285f34848959937307f5859062023-03-21T07:26:14ZengWolters Kluwer Medknow PublicationsAsian Journal of Andrology1008-682X1745-72622023-01-0125222322910.4103/aja202258Identification of senescence-related molecular subtypes and key genes for prostate cancerDe-Chao FengWei-Zhen ZhuXu ShiQiao XiongJia YouQiang WeiLu YangWe identified distinct senescence-related molecular subtypes and critical genes among prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT). We conducted all analyses using R software and its suitable packages. Twelve genes, namely, secreted frizzled-related protein 4 (SFRP4), DNA topoisomerase II alpha (TOP2A), pleiotrophin (PTN), family with sequence similarity 107 member A (FAM107A), C-X-C motif chemokine ligand 14 (CXCL14), prostate androgen-regulated mucin-like protein 1 (PARM1), leucine zipper protein 2 (LUZP2), cluster of differentiation 38 (CD38), cartilage oligomeric matrix protein (COMP), vestigial-like family member 3 (VGLL3), apolipoprotein E (APOE), and aldehyde dehydrogenase 2 family member (ALDH2), were eventually used to subtype PCa patients from The Cancer Genome Atlas (TCGA) database and GSE116918, and the molecular subtypes showed good correlations with clinical features. In terms of the tumor immune environment (TME) analysis, compared with cluster 1, cancer-associated fibroblasts (CAFs) scored significantly higher, while endothelial cells scored lower in cluster 2 in TCGA database. There was a statistically significant correlation between both CAFs and endothelial cells with biochemical recurrence (BCR)-free survival for PCa patients undergoing RP. For the GSE116918 database, cluster 2 had significantly lower levels of CAFs and tumor purity and higher levels of stromal, immune, and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) scores than cluster 1; in addition, patients with high levels of CAFs, stromal scores, immune scores, and ESTIMATE scores and low levels of tumor purity tended to suffer from BCR. Based on the median of differentially expressed checkpoints, high expression of CD96, hepatitis A virus cellular receptor 2 (HAVCR2), and neuropilin 1 (NRP1) in GSE116918 and high expression of CD160 and tumor necrosis factor (ligand) superfamily member 18 (TNFSF18) in TCGA database were associated with a significantly higher risk of BCR than their counterparts. In conclusion, we first constructed distinct molecular subtypes and critical genes for PCa patients undergoing RP or RT from the fresh perspective of senescence.http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=2;spage=223;epage=229;aulast=Fengcellular senescence; immune checkpoints; molecular subtypes; prostate cancer; tumor immune environment
spellingShingle De-Chao Feng
Wei-Zhen Zhu
Xu Shi
Qiao Xiong
Jia You
Qiang Wei
Lu Yang
Identification of senescence-related molecular subtypes and key genes for prostate cancer
Asian Journal of Andrology
cellular senescence; immune checkpoints; molecular subtypes; prostate cancer; tumor immune environment
title Identification of senescence-related molecular subtypes and key genes for prostate cancer
title_full Identification of senescence-related molecular subtypes and key genes for prostate cancer
title_fullStr Identification of senescence-related molecular subtypes and key genes for prostate cancer
title_full_unstemmed Identification of senescence-related molecular subtypes and key genes for prostate cancer
title_short Identification of senescence-related molecular subtypes and key genes for prostate cancer
title_sort identification of senescence related molecular subtypes and key genes for prostate cancer
topic cellular senescence; immune checkpoints; molecular subtypes; prostate cancer; tumor immune environment
url http://www.ajandrology.com/article.asp?issn=1008-682X;year=2023;volume=25;issue=2;spage=223;epage=229;aulast=Feng
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