Comprehensive analysis of prognosis markers with molecular features derived from pan-cancer whole-genome sequences.

IF 3.8 3区医学 Q2 GENETICS & HEREDITY

Human Genomics Pub Date : 2025-04-12 DOI:10.1186/s40246-025-00744-7

Mamoru Kato, Jo Nishino, Momoko Nagai, Hirofumi Rokutan, Daichi Narushima, Hanako Ono, Takanori Hasegawa, Seiya Imoto, Shigeyuki Matsui, Tatsuhiko Tsunoda, Tatsuhiro Shibata

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引用次数: 0

Abstract

Cancer prognosis markers are useful for treatment decisions; however, the omics-level landscape is not well understood across multiple cancer types. Pan-Cancer Analysis of Whole Genomes (PCAWG) provides unprecedented access to various types of molecular data, ranging from typical DNA mutations and RNA expressions to more deeply analyzed or whole-genomic features, such as HLA haplotypes and structural variations. We analyzed the PCAWG data of 13 cancer types from 1,514 patients to identify prognosis markers belonging to 17 molecular features in the survival analysis based on the Cox and Lasso regression methods. We found that germline features including HLA haplotypes, neoantigens, and the number of structural variations were associated with overall survival; however, mutational signatures were not. Measuring a few markers provided a sufficient prognostic performance evaluated by c-index for each cancer type. DNA markers demonstrated better or comparable prognostic performance compared to RNA markers in some cancer types. "Universal" markers strongly associated with overall survival across cancer types were not identified. These findings will give insights into the clinical implementation of prognosis markers.

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泛癌全基因组序列预后标志物分子特征的综合分析。

癌症预后指标对治疗决策有用；然而，在多种癌症类型中，组学水平的情况还没有得到很好的理解。泛癌症全基因组分析（PCAWG）提供了前所未有的获取各种类型分子数据的途径，从典型的DNA突变和RNA表达到更深入分析的全基因组特征，如HLA单倍型和结构变异。我们分析了来自1514例患者的13种癌症类型的PCAWG数据，基于Cox和Lasso回归方法，在生存分析中确定了属于17个分子特征的预后标志物。我们发现，包括HLA单倍型、新抗原和结构变异数量在内的种系特征与总生存率相关；然而，突变签名并非如此。测量一些标志物提供了足够的预后表现，用c指数评估每种癌症类型。在某些癌症类型中，与RNA标记物相比，DNA标记物表现出更好或相当的预后表现。没有发现与各种癌症类型的总体生存率密切相关的“通用”标记。这些发现将为预后标志物的临床应用提供见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Genomics GENETICS & HEREDITY-

CiteScore

6.00

自引率

2.20%

发文量

审稿时长

11 weeks

期刊介绍： Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.