Wu Lawrence W, Deshmukh Sachin Kumar, Wu Sharon, Xiu Joanne, Jang Sung Joo, Park Jimyung, Lam Vincent K, Lou Emil, Goel Sanjay, Shroff Rachna T, Moy Ryan H
Division of Hematology/Oncology, Columbia University Irving Medical Center, New York, NY, USA.
Caris Life Sciences, Phoenix, AZ, USA.
NPJ Precis Oncol. 2025 Jul 17;9(1):241. doi: 10.1038/s41698-025-01030-4.
Using a large real-world database with matched genomic and transcriptomic data, we characterized clinical and molecular differences between patients with early-onset esophagogastric cancer (EOEGC; <50 years), intermediate-onset esophagogastric cancer (IOEGC; 50-65 years), and average-onset esophagogastric cancer (AOEGC; >65 years). We analyzed clinicopathologic, whole transcriptome, and DNA-sequencing data from 5175 patient samples (EOEGC, n = 530; IOEGC, n = 1744; AOEGC, n = 2901) from the Caris Life Sciences database. Immune deconvolution was performed with quanTIseq and pathway enrichment with Gene Set Enrichment Analysis (GSEA). Real-world overall survival was estimated from insurance claims data. Prevalence of EOEGC was higher in patients who were Black, Asian, Hispanic/Latino, and female. Patients with EOEGC had higher proportion of CDH1 mutations; FGFR2, CCNE1, MYC copy number alterations; and ARHGAP26 fusions. Patients with EOEGC had decreased prevalence of immune-oncology markers of microsatellite instability-high, tumor mutation burden-high, and PD-L1 positivity. Immune microenvironment analysis identified significant enrichment of M2 macrophages and decreased M1 macrophages in patients with EOEGC. GSEA identified enrichment of epithelial mesenchymal transition and coagulation pathways in patients with EOEGC. This large real-world characterization of age-stratified esophagogastric cancer found that EOEGC was associated with significant racial, ethnic, and gender differences, and notable molecular differences that may have prognostic and therapeutic implications.
利用一个包含匹配基因组和转录组数据的大型真实世界数据库，我们对早发性食管癌（EOEGC；<50岁）、中年发性食管癌（IOEGC；50 - 65岁）和晚发性食管癌（AOEGC；>65岁）患者之间的临床和分子差异进行了特征分析。我们分析了来自Caris生命科学数据库的5175例患者样本（EOEGC，n = 530；IOEGC，n = 1744；AOEGC，n = 2901）的临床病理、全转录组和DNA测序数据。使用quanTIseq进行免疫反卷积分析，并使用基因集富集分析（GSEA）进行通路富集分析。从保险理赔数据中估计真实世界的总生存期。EOEGC在黑人、亚洲人、西班牙裔/拉丁裔和女性患者中的患病率较高。EOEGC患者中CDH1突变比例较高；FGFR2、CCNE1、MYC拷贝数改变；以及ARHGAP26融合。EOEGC患者中微卫星高度不稳定、肿瘤突变负荷高和PD-L1阳性的免疫肿瘤学标志物患病率降低。免疫微环境分析发现EOEGC患者中M2巨噬细胞显著富集，M1巨噬细胞减少。GSEA分析发现EOEGC患者中上皮间质转化和凝血通路富集。这项对年龄分层的食管癌进行的大型真实世界特征分析发现，EOEGC与显著的种族、民族和性别差异以及可能具有预后和治疗意义的显著分子差异相关。
