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端粒维持相关基因对膀胱癌的生存预测和亚型识别很重要。

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

作者信息

Xiao Yonggui, Xu Danping, Jiang Chonghao, Huili Youlong, Nie Shiwen, Zhu Hongfei, Fan Guorui, Guan Xiaohai

机构信息

Affiliated Hospital of North China University of Science and Technology, Tangshan, China.

Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China.

出版信息

Front Genet. 2023 Jan 6;13:1087246. doi: 10.3389/fgene.2022.1087246. eCollection 2022.

Abstract

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. 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. 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. 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.

摘要

膀胱癌的发病率和死亡率在泌尿外科领域均位居前三。端粒维持相关基因与膀胱癌的发生和发展密切相关,在膀胱癌患者中通常可发现约60%-80%的端粒维持基因突变。通过limma R包获得端粒维持相关基因表达谱。在筛选出的359个差异基因中,通过单变量独立预后分析获得17个与预后相关的基因,然后进行LASSO回归分析。选择最佳结果输出模型公式,获得11个与模型相关的基因。将TCGA队列作为内部组,GEO数据集作为外部组,对模型进行外部验证。然后,使用HPA数据库查询11个模型基因的免疫组化情况。将模型评分与临床信息相结合,绘制了列线图。同时,我们对膀胱癌的免疫图谱和药物敏感性进行了深入分析。参考矩阵热图、delta面积图、一致性累积分布函数图和追踪图,我们将样本进一步分为两个亚型并进行深入研究。利用生物信息学,我们获得了一个端粒维持相关基因的预后模型。通过内部组和外部组的验证,我们认为该模型能够稳定地预测膀胱癌患者的生存情况。通过HPA数据库,我们发现ABCC9、AHNAK和DIP2C这三个基因在肿瘤患者中表达较低,另外八个基因——PLOD1、SLC3A2、RUNX2、RAD9A、CHMP4C、DARS2、CLIC3和POU5F1——在肿瘤患者中高表达。该模型对不同临床病理特征的人群具有准确的预测能力。通过列线图,我们可以轻松评估患者的生存率。临床医生可以根据患者生存、免疫检测和药物敏感性分析的预测结果,为患者制定有针对性的诊断和治疗方案。不同的亚型有助于进一步细分患者,以达到更好的治疗目的。根据本研究列线图获得的结果,结合患者免疫分析和药物敏感性分析的结果,临床医生可以为患者制定诊断和个性化治疗方案。不同的亚型可用于进一步细分患者,以制定更精确的治疗方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fddd/9853053/367b06187f77/fgene-13-1087246-g001.jpg

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