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TSPAN1、KIAA1324 和 ESRP1 在前列腺癌中的预后作用。

Prognostic role of TSPAN1, KIAA1324 and ESRP1 in prostate cancer.

机构信息

Institute of Pathology, University Hospital Bonn, Bonn, Germany.

Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

出版信息

APMIS. 2021 Apr;129(4):204-212. doi: 10.1111/apm.13117. Epub 2021 Feb 2.

Abstract

The aim of this study was to validate prostate cancer-associated genes on transcript level and to assess the prognostic value of the most promising markers by immunohistochemistry. Based on differentially expressed genes found in a previous study, 84 genes were further validated using mRNA expression data and follow-up information from the Cancer Genome Atlas (TCGA) prostate cancer cohort (n = 497). Immunohistochemistry was used for validation of three genes in an independent, clinically annotated prostatectomy patient cohort (n = 175) with biochemical relapse as endpoint. Also, associations with clinicopathological variables were evaluated. Eleven protein-coding genes from the list of 84 genes were associated with biochemical recurrence-free survival on mRNA expression level in multivariate Cox-analyses. Three of these genes (TSPAN1, ESRP1 and KIAA1324) were immunohistochemically validated using an independent cohort of prostatectomy patients. Both ESRP1 and KIAA1324 were independently associated with biochemical recurrence-free survival. TSPAN1 was univariately prognostic but failed significance on multivariate analysis, probably due to its strong correlation with high Gleason scores. Multistep filtering using the publicly available TCGA cohort, data of an earlier expression profiling study which profiled 3023 cancer-associated transcripts in 42 primary prostate cancer cases, identified two novel candidate prognostic markers (ESRP1 and KIAA1324) of primary prostate cancer for further study.

摘要

本研究旨在通过免疫组织化学验证转录水平上的前列腺癌相关基因,并评估最有前途的标志物的预后价值。基于之前研究中发现的差异表达基因,使用 mRNA 表达数据和癌症基因组图谱(TCGA)前列腺癌队列(n=497)的随访信息进一步验证了 84 个基因。使用免疫组织化学方法在具有生化复发终点的独立、临床注释前列腺切除术患者队列(n=175)中验证了三个基因。还评估了与临床病理变量的关联。在多变量 Cox 分析中,84 个基因列表中的 11 个编码蛋白的基因与 mRNA 表达水平上的生化无复发生存率相关。这三个基因(TSPAN1、ESRP1 和 KIAA1324)使用前列腺切除术患者的独立队列进行了免疫组织化学验证。ESRP1 和 KIAA1324 均与生化无复发生存率独立相关。TSPAN1 是单变量预后因素,但在多变量分析中未达到显著水平,可能是由于其与高 Gleason 评分有很强的相关性。使用公开的 TCGA 队列进行多步筛选,以及对 42 例原发性前列腺癌病例中的 3023 个癌症相关转录本进行的早期表达谱研究的数据,鉴定了两个新的候选原发性前列腺癌预后标志物(ESRP1 和 KIAA1324),用于进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e5b/7986212/bbc56b6ec254/APM-129-204-g002.jpg

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