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FGFR1放大结直肠癌:通过综合基因组和免疫组织化学分析确定一个独特的预后亚型

X Lyu ¹, R Cai ², B Han ³

¹Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China.
²Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China.
³Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
⁵Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China; Department of Radiology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.

⁰Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangzhou, China.

ESMO Open +

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2025年八月20日

在PubMed上查看摘要

概括

纤维细胞生长因子受体 (FGFR) 变化,特别是FGFR1放大,在结直肠癌 (CRC) 中很常见,预测存活率较低. 免疫组织化学评分系统为FGFR1驱动的CRC提供了可行的查方法.

科学领域

癌症学
遗传学
分子生物学

背景情况

纤维细胞生长因子受体 (FGFR) 变化是胆管癌和泌尿器癌的关键治疗点.
在结肠直肠癌 (CRC) 中,FGFR的变化未得到充分研究.

研究的目的

调查FGFR变化的流行情况.
与临床病理特征相关联的FGFR变化.
确定FGFR变化的预后影响.

主要方法

使用下一代测序 (NGS) 和免疫组织化学 (IHC) 分析了608个I-IV阶段的CRC样本.
通过卡普兰-梅尔和考克斯回归,与生存结果相关联的FGFR基因组状况.
使用19个公共数据集 (n=6998) 和癌症基因组图谱 (TCGA) COREAD数据集 (n=640) 的验证结果.

主要成果

确定FGFR1放大 (3.8%的患病率) 是CRC中占主导地位的FGFR变化 (n=7606).
FGFR变化独立预测了不良的无病存活率 (DFS; HR 2.58) 和无病进展的存活率 (PFS; HR 2. 17).
FGFR1放大显示出最强的预后影响 (DFS HR 2. 91,PFS HR 2.52);预后大小与KRAS/ BRAF突变相美.
开发了一种针对FGFR1查的免疫反应评分 (IRS) 系统,与NGS一致95. 2%.

结论

FGFR1放大是CRC中占主导地位的FGFR变化,与侵袭性临床行为和低生存率相关.
在CRC中,FGFR的变化是显著的预后标志物,类似于KRAS/ BRAF突变.
经过验证的基于IHC的IRS系统为识别FGFR1驱动的CRC提供了具有成本效益和临床可行的替代方案.

关键词:

大肠直肠癌 (CRC) 纤维细胞生长因子受体 (FGFR) 下一代测序 (NGS) 预后生物标志物针对性的治疗