食道鳞癌（ESCC）预后较差，是最致命的胃肠恶性肿瘤之一。尽管已进行了大量的转录组学研究以了解其分子基础，但人群特异性差异对该疾病的影响尚未探明。本研究旨在调查来自六个不同全球人群的ESCC样本中基因表达模式的人群特异性差异，识别差异表达基因（DEGs）及其相关通路，并发现ESCC诊断和预后的潜在生物标志物。另外，本研究还分析了ESCC中的人群特异性微生物和化学危险因素。我们通过分析微阵列数据比较了来自六个不同全球人群的ESCC样本的基因表达模式。为了识别DEGs，我们进行了严格的质量控制并采用线性建模。我们将每个人群得到的DEG列表与ESCC ATLAS进行了交叉比较，以识别已知和新颖的DEGs。我们使用The Cancer Genome Atlas Program（TCGA）数据进行生存分析，以识别与ESCC诊断和预后相关的潜在生物标志物。最后，我们进行了比较功能富集和毒基因组分析。我们报告了19个具有不同表达模式的基因，表明ESCC存在人群特异性差异。此外，我们还发现了166个新颖的DEGs，例如ENDOU、SLCO1B3、KCNS3、IFI35等。生存分析确定了三个对ESCC生存至关重要的新颖基因（CHRM3、CREG2、H2AC6）。值得注意的是，我们的研究结果显示，ESCC的DEGs中存在与细胞外基质（ECM）相关的基因本体术语和通路的显著富集现象。我们还发现了与免疫反应和微生物感染相关的人群特异性差异的通路，其中包括富集HPV、阿米巴病、利什曼病和人巨细胞病毒相关的基因。我们的毒基因组分析确定了烟草吸烟作为主要危险因素，并且顺铂作为与各人群DEGs相互作用最多的主要药物化学物质。本研究揭示了ESCC中基因表达模式的人群特异性差异及其相关通路的新见解。我们的研究结果表明，细胞外基质（ECM）组织的变化对该癌症的发展和进展可能至关重要，并且环境和遗传因素在该疾病中发挥重要作用。所识别出的新颖DEGs可能成为诊断、预后和治疗的潜在生物标志物。©2023年。BioMed Central Ltd.的一部分，隶属于Springer Nature。

Esophageal squamous cell carcinoma (ESCC) has a poor prognosis and is one of the deadliest gastrointestinal malignancies. Despite numerous transcriptomics studies to understand its molecular basis, the impact of population-specific differences on this disease remains unexplored.This study aimed to investigate the population-specific differences in gene expression patterns among ESCC samples obtained from six distinct global populations, identify differentially expressed genes (DEGs) and their associated pathways, and identify potential biomarkers for ESCC diagnosis and prognosis. In addition, this study deciphers population specific microbial and chemical risk factors in ESCC.We compared the gene expression patterns of ESCC samples from six different global populations by analyzing microarray datasets. To identify DEGs, we conducted stringent quality control and employed linear modeling. We cross-compared the resulting DEG lists of each populations along with ESCC ATLAS to identify known and novel DEGs. We performed a survival analysis using The Cancer Genome Atlas Program (TCGA) data to identify potential biomarkers for ESCC diagnosis and prognosis among the novel DEGs. Finally, we performed comparative functional enrichment and toxicogenomic analysis.Here we report 19 genes with distinct expression patterns among populations, indicating population-specific variations in ESCC. Additionally, we discovered 166 novel DEGs, such as ENDOU, SLCO1B3, KCNS3, IFI35, among others. The survival analysis identified three novel genes (CHRM3, CREG2, H2AC6) critical for ESCC survival. Notably, our findings showed that ECM-related gene ontology terms and pathways were significantly enriched among the DEGs in ESCC. We also found population-specific variations in immune response and microbial infection-related pathways which included genes enriched for HPV, Ameobiosis, Leishmaniosis, and Human Cytomegaloviruses. Our toxicogenomic analysis identified tobacco smoking as the primary risk factor and cisplatin as the main drug chemical interacting with the maximum number of DEGs across populations.This study provides new insights into population-specific differences in gene expression patterns and their associated pathways in ESCC. Our findings suggest that changes in extracellular matrix (ECM) organization may be crucial to the development and progression of this cancer, and that environmental and genetic factors play important roles in the disease. The novel DEGs identified may serve as potential biomarkers for diagnosis, prognosis and treatment.© 2023. BioMed Central Ltd., part of Springer Nature.