Identification of clinicopathological-specific driver gene and genetic subtyping of colorectal cancer.

IF 5.7 2区医学 Q1 Medicine Cancer Science Pub Date : 2025-01-11 DOI:10.1111/cas.16432

Jianjiong Li, Chunnian Wang, Changshun Yang, Hua Bao, Ningyou Li, Xianqiang Huang, Wei Gong, Xinyue Hong, Jiani C Yin, Jiaohui Pang, Meifu Gan, Danping Yuan

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Abstract

This study analyzed targeted sequencing data from 6530 tissue samples from patients with metastatic Chinese colorectal cancer (CRC) to identify low mutation frequency and subgroup-specific driver genes, using three algorithms for overall CRC as well as across different clinicopathological subgroups. We analyzed 425 cancer-related genes, identifying 101 potential driver genes, including 36 novel to CRC. Notably, some genes demonstrated subgroup specificity; for instance, ERBB4 was found as a male-specific driver gene and mutations of ERBB4 only influenced the prognosis of male patients with CRC. This sex disparity of ERBB4 was validated in an independent large-scale Memorial Sloan Kettering Cancer Center CRC cohort with 2444 samples. Furthermore, using network-based stratification based on protein-protein interaction, we classified the microsatellite stable (MSS) and unstable (MSI) CRCs into six and three major subtypes, respectively, each showing unique phenotypes and prognoses. In MSS CRC, cluster 5 (APCAMER1-KRAS) and cluster 2 (RNF43-BRAF-PIK3CA) were predominant, and cluster 5 showed a superior overall survival compared with cluster 2. This extensive heterogeneity in driver gene mutations underscores the complexity of CRC and suggests significant implications for treatment and prognostic assessments.

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结直肠癌临床病理特异性驱动基因的鉴定及遗传分型。

本研究分析了来自中国转移性结直肠癌（CRC）患者的6530个组织样本的靶向测序数据，以确定低突变频率和亚组特异性驱动基因，使用三种算法用于总体CRC以及不同临床病理亚组。我们分析了425个癌症相关基因，确定了101个潜在的驱动基因，其中36个是CRC的新基因。值得注意的是，一些基因表现出亚群特异性；例如，ERBB4被发现是男性特有的驱动基因，ERBB4的突变仅影响男性结直肠癌患者的预后。ERBB4的这种性别差异在一个独立的大型纪念斯隆凯特琳癌症中心CRC队列中得到了验证，该队列有2444个样本。此外，利用基于蛋白-蛋白相互作用的网络分层，我们将微卫星稳定型（MSS）和不稳定型（MSI） crc分别分为6个和3个主要亚型，每个亚型都表现出独特的表型和预后。在MSS CRC中，簇5 （APCAMER1-KRAS）和簇2 （RNF43-BRAF-PIK3CA）占主导地位，簇5的总生存率高于簇2。驱动基因突变的广泛异质性强调了结直肠癌的复杂性，并对治疗和预后评估具有重要意义。

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

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.