Table_1_Comparative genomic analysis of esophageal squamous cell carcinoma among different geographic regions.csv

IntroductionEsophageal squamous cell carcinoma (ESCC) shows remarkable variation in incidence, survival, and risk factors. Although the genomic characteristics of ESCC have been extensively characterized, the genomic differences between different geographic regions remain unclear.
MethodsIn this study, we sequenced 111 patients with ESCC from northern (NC) and southern (SC) China, combined their data with those of 1081 cases from previous reports, and performed a comparative analysis among different regions. In total, 644 ESCC cases were collected from six geographic regions (NC, SC, Xinjiang, China [XJC], Japan [JP], Vietnam [VN], and Europe & America [EA]) as the discovery cohort. Validation cohort 1 included 437 patients with ESCC from the NC region. Validation cohort 2 included 54 and 57 patients from the NC and SC regions, respectively.
ResultsPatients with ESCC in different regions had different genomic characteristics, including DNA signatures, tumor mutation burdens, significantly mutated genes (SMGs), altered signaling pathways, and genes associated with clinical features. Based on both the DNA mutation signature and the mutation profile of the most common genes, the NC and SC groups were clustered close together, followed by the JP, XJC, EA, and VN groups. Compared to patients with ESCC from SC, SMGs, including KMT2D, FAT1, and NOTCH1 were more frequently identified in patients with ESCC from NC. Furthermore, some genes (TDG and DNAH8) correlated with overall survival in completely opposite ways in patients with ESCC from different geographical regions.
ConclusionsOur study provides insights into genomic differences in ESCC among different regions. These differences may be related to differences in environmental carcinogens, incidence, and survival.

引言
食管鳞状细胞癌（Esophageal squamous cell carcinoma, ESCC）的发病率、生存率及危险因素存在显著异质性。尽管目前已对ESCC的基因组特征进行了广泛解析，但不同地理区域间的基因组差异仍未明确。
方法
本研究对来自中国北方（northern China, NC）与中国南方（southern China, SC）的111例ESCC患者进行测序，并将其数据与既往报道的1081例患者数据整合，开展不同区域间的比较分析。本研究的发现队列共纳入来自6个地理区域的644例ESCC患者，分别为中国北方、中国南方、中国新疆（Xinjiang, China, XJC）、日本（Japan, JP）、越南（Vietnam, VN）及欧美（Europe & America, EA）。验证队列1包含来自中国北方的437例ESCC患者；验证队列2分别包含中国北方54例、中国南方57例ESCC患者。
结果
不同地理区域的ESCC患者具有不同的基因组特征，包括DNA突变特征、肿瘤突变负荷、显著突变基因（significantly mutated genes, SMGs）、异常调控的信号通路以及与临床特征相关的基因。基于DNA突变特征及常见基因的突变谱进行聚类分析，中国北方与中国南方患者聚为一类，随后依次为日本、中国新疆、欧美及越南患者。与中国南方患者相比，中国北方患者中KMT2D、FAT1及NOTCH1等显著突变基因的检出频率更高。此外，TDG与DNAH8等基因在不同地理区域的ESCC患者中，与总生存期的相关性呈现完全相反的趋势。
结论
本研究揭示了不同地理区域ESCC患者间的基因组差异，这些差异可能与环境致癌物、发病率及生存率的差异相关。