PO.CL09.01 · 临床研究
早发性与平均发病年龄胃癌的真实世界临床基因组比较
Real-world clinicogenomic comparison of early- and average- onset gastric cancer
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
近几十年来，年轻个体中的胃癌发病率出现了前所未有的上升，而老年个体中则呈下降趋势。然而，年轻个体胃癌的生物学基础仍知之甚少。我们描述了早发性胃癌（EOGC）与平均发病年龄胃癌（AOGC）相比的临床病理和基因组特征。我们利用多机构前瞻性肿瘤学研究信息交换网络（ORIEN）数据库，分析了311例患者，以比较EOGC（<50岁；N=72）与AOGC（>50岁，N=239）之间的人口学、临床病理、基因组和生存结局。分析并比较了两个队列之间的基因组、胚系和RNA测序数据。同时也处理了突变和免疫签名。EOGC患者在诊断时表现出显著更高的疼痛发生率（53% vs 30%，p=0.001），但贫血或反流并无差异。EOGC患者更可能表现为III/IV期疾病（70% vs 45%，p=0.006）和弥漫型/印戒细胞组织学（47% vs 16%，p=0.002）。因此，年轻队列的OS降低（HR 1.52；p=0.03）。年轻患者的体细胞突变负荷降低。整个队列中显著突变的基因包括CDH1、ARID1A、TP53、PIK3CA，但CDH1在EOGC队列中突变更为频繁（40% vs 18%，p=0.09）。观察到RNA表达的显著差异，上皮间质转化（EMT）、肌生成和顶端连接上调。免疫解卷积揭示M2巨噬细胞、肥大细胞和CD4+ T细胞亚群占主导，但队列间无差异。早发性胃癌具有独特的临床和基因组特征。EOGC中的通路失调可能促进肿瘤发生和治疗耐药。本研究强调了进一步研究年轻个体新型治疗、生物标志物发现和早期检测方法学的必要性。
查看英文原文 English abstract
In recent decades, there has been an unprecedented rise in gastric cancer among younger individuals, contrasting with a decline among older individuals. However, the biological underpinnings of gastric cancer in younger individuals remain poorly understood. We described the clinicopathologic and genomic characteristics of early-onset gastric cancer (EOGC) compared to average-onset gastric cancer (AOGC). We analyzed 311 patients using the multi-institutional prospective Oncology Research Information Exchange Network (ORIEN) database to compare demographic, clinicopathologic, genomic, and survival outcomes between EOGC (<50 years; N=72) vs AOGC (>50 years N=239). Genomic, germline, and RNA sequencing data were analyzed and compared between the cohorts. Mutational and immune signatures were also processed. EOGC patients exhibited significantly higher rates of pain at diagnosis (53% vs 30% p=0.001 ), but not anemia or reflux. EOGC patients were more likely to present with stage III/IV disease (70% vs 45% p=0.006 ) and diffuse/signet ring histology (47% vs 16% p=0.002 ). Consequently, OS was decreased in the younger cohort (HR 1.52; p=0.03). Somatic mutational load was decreased in young patients. Significantly mutated genes in the entire cohort included CDH1 , ARID1A , TP53 , PIK3CA, but CDH1 was more frequently mutated in the EOGC cohort (40% vs 18% p=0.09 ). Significant differences in RNA expression were observed, with upregulated epithelial mesenchymal transition (EMT), myogenesis, and apical junction. Immune deconvolution revealed a predominance of M2 macrophages, mast cells, and CD4 + T cell subsets, but no differences between cohorts. Early-onset gastric cancer has unique clinical and genomic features. Pathway dysregulation in EOGC may contribute to tumorigenesis and therapy resistance. This study underscores the necessity for further research into novel therapies, biomarker discovery, and early detection methodologies in younger individuals.
利益披露 Disclosure
H. McDonald, None..
L. Turcios, None..
N. Hosamani, None..
A. Faisal, None..
C. Wang, None..
J. Kim, None..
M. Barry-Hundeyin, None.