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通过下一代测序确定的膀胱癌预测性分子生物标志物——初步数据

Predictive Molecular Biomarkers of Bladder Cancer Identified by Next-Generation Sequencing-Preliminary Data.

作者信息

Myszka Aleksander, Ciesla Marek, Siekierzynska Aleksandra, Sendera Anna, Constantinou Constantina, Karpinski Pawel, Wysiadecki Grzegorz, Balawender Krzysztof

机构信息

Institute of Medical Sciences, University of Rzeszow, 35-310 Rzeszow, Poland.

Department of Biotechnology and Plant Physiology, University of Rzeszow, 35-601 Rzeszow, Poland.

出版信息

J Clin Med. 2024 Dec 17;13(24):7701. doi: 10.3390/jcm13247701.

Abstract

The majority of patients with bladder cancer suffer from tumour recurrence. Identifying prognostic factors for tumour recurrence is crucial for treatment and follow-up in affected patients. The study aimed to assess the impact of somatic mutations in bladder cancer on patient outcomes and tumour recurrence. The study group comprised 46 patients with urothelial bladder cancers referred for transurethral resection of the tumour. A molecular study on tumour-derived DNA was performed using next-generation sequencing. Somatic mutations were screened in 50 genes involved in carcinogenesis. We identified 81 variants in 23 genes, including 54 pathogenic mutations, 18 likely pathogenic variants, and 9 variants of unknown significance. The most frequently mutated genes were , , and in 52%, 35%, and 24% of tumours, respectively. The average tumour-free survival was significantly longer in cases with mutations in the gene ( = 0.02), and mutations in the gene were associated with a decreased risk of tumour recurrence (Hazard Ratio = 0.26; 95% CI: 0.11-0.62; = 0.018). The gene was shown to be a predictive marker of a low risk of bladder tumour recurrence. Molecular screening of bladder cancers supported predictive biomarkers of tumour recurrence and showed that tumour-free survival is molecularly determined.

摘要

大多数膀胱癌患者会出现肿瘤复发。识别肿瘤复发的预后因素对于受影响患者的治疗和随访至关重要。该研究旨在评估膀胱癌体细胞突变对患者预后和肿瘤复发的影响。研究组包括46例因肿瘤行经尿道切除术的尿路上皮膀胱癌患者。使用下一代测序技术对肿瘤来源的DNA进行了分子研究。在50个参与致癌作用的基因中筛选体细胞突变。我们在23个基因中鉴定出81个变异,包括54个致病性突变、18个可能的致病性变异和9个意义不明的变异。最常发生突变的基因分别在52%、35%和24%的肿瘤中为 、 和 。 基因发生突变的病例平均无瘤生存期明显更长( = 0.02), 基因的突变与肿瘤复发风险降低相关(风险比 = 0.26;95%置信区间:0.11 - 0.62; = 0.018)。 基因被证明是膀胱肿瘤复发低风险的预测标志物。膀胱癌的分子筛查支持肿瘤复发的预测生物标志物,并表明无瘤生存期是由分子决定的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3624/11677048/490e2e9e9fe5/jcm-13-07701-g001.jpg

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