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A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer
BACKGROUND: We aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa). METHODS: We used Lasso and Cox regression analysis to establish the EMTGPI. All analyse...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790245/ https://www.ncbi.nlm.nih.gov/pubmed/35096608 http://dx.doi.org/10.3389/fonc.2021.805571 |
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author | Feng, Dechao Shi, Xu Xiong, Qiao Zhang, Facai Li, Dengxiong Yang, Lu |
author_facet | Feng, Dechao Shi, Xu Xiong, Qiao Zhang, Facai Li, Dengxiong Yang, Lu |
author_sort | Feng, Dechao |
collection | PubMed |
description | BACKGROUND: We aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa). METHODS: We used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages. RESULTS: We established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887. CONCLUSIONS: We concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa. |
format | Online Article Text |
id | pubmed-8790245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87902452022-01-27 A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer Feng, Dechao Shi, Xu Xiong, Qiao Zhang, Facai Li, Dengxiong Yang, Lu Front Oncol Oncology BACKGROUND: We aimed to establish a novel epithelial-mesenchymal transition (EMT)-related gene prognostic index (EMTGPI) associated with biochemical recurrence (BCR) and drug resistance for prostate cancer (PCa). METHODS: We used Lasso and Cox regression analysis to establish the EMTGPI. All analyses were conducted with R version 3.6.3 and its suitable packages. RESULTS: We established the EMTGPI based on SFRP4 and SPP1. Patients in high-risk group had 2.23 times of BCR risk than those in low-risk group (p = 0.003), as well as 2.36 times of metastasis risk (p = 0.053). In external validation, we detected similar diagnostic efficacy and prognostic value in terms of BCR free survival. For drug resistance, we observe moderately diagnostic accuracy of EMTGPI score (AUC: 0.804). We found that PDCD1LG2 (p = 0.04) and CD96 (p = 0.01) expressed higher in BCR patients compared with their counterpart. For TME analysis, we detected that CD8+ T cells and M1 macrophages expressed higher in BCR group. Moreover, stromal score (p = 0.003), immune score (p = 0.01), and estimate score (p = 0.003) were higher in BCR patients. We found that EMTGPI was significantly related to HAVCR2 (r: 0.34), CD96 (r: 0.26), CD47 (r: 0.22), KIR3DL1 (r: −0.21), KLRD1 (r: −0.21), and CD2 (r: 0.21). In addition, we observed that EMTGPI was significantly associated with M1 macrophages (r: 0.6), M2 macrophages (r: −0.33), monocytes (r: −0.18), neutrophils (r: −0.43), CD8+ T cells (r: 0.13), and dendritic cells (r: 0.37). PHA-793887 was the common drug sensitive to SPP1 and SFRP4, and PC3 and DU145 were the common PCa-related cell lines of SPP1, SFRP4, and PHA-793887. CONCLUSIONS: We concluded that the EMTGPI score based on SFRP4 and SPP1 could be used to predict BCR for PCa patients. We confirmed the impact of immune evasion on the BCR process of PCa. Frontiers Media S.A. 2022-01-12 /pmc/articles/PMC8790245/ /pubmed/35096608 http://dx.doi.org/10.3389/fonc.2021.805571 Text en Copyright © 2022 Feng, Shi, Xiong, Zhang, Li and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Feng, Dechao Shi, Xu Xiong, Qiao Zhang, Facai Li, Dengxiong Yang, Lu A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer |
title | A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer |
title_full | A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer |
title_fullStr | A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer |
title_full_unstemmed | A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer |
title_short | A Gene Prognostic Index Associated With Epithelial-Mesenchymal Transition Predicting Biochemical Recurrence and Tumor Chemoresistance for Prostate Cancer |
title_sort | gene prognostic index associated with epithelial-mesenchymal transition predicting biochemical recurrence and tumor chemoresistance for prostate cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8790245/ https://www.ncbi.nlm.nih.gov/pubmed/35096608 http://dx.doi.org/10.3389/fonc.2021.805571 |
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