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Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer

Background: Bladder cancer ranks among the top three in the urology field for both morbidity and mortality. Telomere maintenance-related genes are closely related to the development and progression of bladder cancer, and approximately 60%–80% of mutated telomere maintenance genes can usually be foun...

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Autores principales: Xiao, Yonggui, Xu, Danping, Jiang, Chonghao, Huili, Youlong, Nie, Shiwen, Zhu, Hongfei, Fan, Guorui, Guan, Xiaohai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853053/
https://www.ncbi.nlm.nih.gov/pubmed/36685927
http://dx.doi.org/10.3389/fgene.2022.1087246
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author Xiao, Yonggui
Xu, Danping
Jiang, Chonghao
Huili, Youlong
Nie, Shiwen
Zhu, Hongfei
Fan, Guorui
Guan, Xiaohai
author_facet Xiao, Yonggui
Xu, Danping
Jiang, Chonghao
Huili, Youlong
Nie, Shiwen
Zhu, Hongfei
Fan, Guorui
Guan, Xiaohai
author_sort Xiao, Yonggui
collection PubMed
description Background: Bladder cancer ranks among the top three in the urology field for both morbidity and mortality. Telomere maintenance-related genes are closely related to the development and progression of bladder cancer, and approximately 60%–80% of mutated telomere maintenance genes can usually be found in patients with bladder cancer. Methods: Telomere maintenance-related gene expression profiles were obtained through limma R packages. Of the 359 differential genes screened, 17 prognostically relevant ones were obtained by univariate independent prognostic analysis, and then analysed by LASSO regression. The best result was selected to output the model formula, and 11 model-related genes were obtained. The TCGA cohort was used as the internal group and the GEO dataset as the external group, to externally validate the model. Then, the HPA database was used to query the immunohistochemistry of the 11 model genes. Integrating model scoring with clinical information, we drew a nomogram. Concomitantly, we conducted an in-depth analysis of the immune profile and drug sensitivity of the bladder cancer. Referring to the matrix heatmap, delta area plot, consistency cumulative distribution function plot, and tracking plot, we further divided the sample into two subtypes and delved into both. Results: Using bioinformatics, we obtained a prognostic model of telomere maintenance-related genes. Through verification with the internal and the external groups, we believe that the model can steadily predict the survival of patients with bladder cancer. Through the HPA database, we found that three genes, namely ABCC9, AHNAK, and DIP2C, had low expression in patients with tumours, and eight other genes—PLOD1, SLC3A2, RUNX2, RAD9A, CHMP4C, DARS2, CLIC3, and POU5F1—were highly expressed in patients with tumours. The model had accurate predictive power for populations with different clinicopathological features. Through the nomogram, we could easily assess the survival rate of patients. Clinicians can formulate targeted diagnosis and treatment plans for patients based on the prediction results of patient survival, immunoassays, and drug susceptibility analysis. Different subtypes help to further subdivide patients for better treatment purposes. Conclusion: According to the results obtained by the nomogram in this study, combined with the results of patient immune-analysis and drug susceptibility analysis, clinicians can formulate diagnosis and personalized treatment plans for patients. Different subtypes can be used to further subdivide the patient for a more precise treatment plan.
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spelling pubmed-98530532023-01-21 Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer Xiao, Yonggui Xu, Danping Jiang, Chonghao Huili, Youlong Nie, Shiwen Zhu, Hongfei Fan, Guorui Guan, Xiaohai Front Genet Genetics Background: Bladder cancer ranks among the top three in the urology field for both morbidity and mortality. Telomere maintenance-related genes are closely related to the development and progression of bladder cancer, and approximately 60%–80% of mutated telomere maintenance genes can usually be found in patients with bladder cancer. Methods: Telomere maintenance-related gene expression profiles were obtained through limma R packages. Of the 359 differential genes screened, 17 prognostically relevant ones were obtained by univariate independent prognostic analysis, and then analysed by LASSO regression. The best result was selected to output the model formula, and 11 model-related genes were obtained. The TCGA cohort was used as the internal group and the GEO dataset as the external group, to externally validate the model. Then, the HPA database was used to query the immunohistochemistry of the 11 model genes. Integrating model scoring with clinical information, we drew a nomogram. Concomitantly, we conducted an in-depth analysis of the immune profile and drug sensitivity of the bladder cancer. Referring to the matrix heatmap, delta area plot, consistency cumulative distribution function plot, and tracking plot, we further divided the sample into two subtypes and delved into both. Results: Using bioinformatics, we obtained a prognostic model of telomere maintenance-related genes. Through verification with the internal and the external groups, we believe that the model can steadily predict the survival of patients with bladder cancer. Through the HPA database, we found that three genes, namely ABCC9, AHNAK, and DIP2C, had low expression in patients with tumours, and eight other genes—PLOD1, SLC3A2, RUNX2, RAD9A, CHMP4C, DARS2, CLIC3, and POU5F1—were highly expressed in patients with tumours. The model had accurate predictive power for populations with different clinicopathological features. Through the nomogram, we could easily assess the survival rate of patients. Clinicians can formulate targeted diagnosis and treatment plans for patients based on the prediction results of patient survival, immunoassays, and drug susceptibility analysis. Different subtypes help to further subdivide patients for better treatment purposes. Conclusion: According to the results obtained by the nomogram in this study, combined with the results of patient immune-analysis and drug susceptibility analysis, clinicians can formulate diagnosis and personalized treatment plans for patients. Different subtypes can be used to further subdivide the patient for a more precise treatment plan. Frontiers Media S.A. 2023-01-06 /pmc/articles/PMC9853053/ /pubmed/36685927 http://dx.doi.org/10.3389/fgene.2022.1087246 Text en Copyright © 2023 Xiao, Xu, Jiang, Huili, Nie, Zhu, Fan and Guan. 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 Genetics
Xiao, Yonggui
Xu, Danping
Jiang, Chonghao
Huili, Youlong
Nie, Shiwen
Zhu, Hongfei
Fan, Guorui
Guan, Xiaohai
Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
title Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
title_full Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
title_fullStr Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
title_full_unstemmed Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
title_short Telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
title_sort telomere maintenance-related genes are important for survival prediction and subtype identification in bladder cancer
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9853053/
https://www.ncbi.nlm.nih.gov/pubmed/36685927
http://dx.doi.org/10.3389/fgene.2022.1087246
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