目的：本文旨在探讨女性胃癌中的病理及预后特征，并基于Meta分析、多中心数据研究女性胃癌患者与男性胃癌患者在临床病理学、预后方面的差异。最后进一步分析女性胃癌患者的分子特征特点。

材料与方法：系统检索PubMed、Cochrane Library、Embase和Web of Science截至2022年6月发表的与性别差异相关的胃癌临床研究。回顾性纳入了2000年1月至2020年12月期间来自中国国家癌症中心、兰州大学第一医院、兰州大学第二医院以及甘肃省肿瘤医院四个胃癌队列中的胃癌患者。基于GEO（the Gene Expression Omnibus）数据库，构建女性胃癌患者的基因表达图谱，并比较女性胃癌患者与女性非胃癌患者之间的基因特征差异。

结果：Meta分析共纳入76篇文献，775,003例胃癌患者。Meta分析结果表明，女性在胃癌患者中的占比相对男性更少（比值比[OR，Odds ratios] = 0.27，95% CI：0.26-0.29，P < 0.00001，I² = 99%）。与男性患者相比，女性胃癌患者的年龄更小，并且在远端胃癌、非贲门胃癌、未分化癌、弥漫型胃癌以及印戒细胞癌的类型中占比更高（均P < 0.00001）。此外，与男性胃癌患者相比，女性胃癌患者的3年和5年总生存率（OS，Overall survival）相对更好（风险比[HR，Hazard ratio] = 0.90，95%置信区间[CI，Confidence interval]：0.86-0.95，P = 0.003，I² = 53%；HR = 0.86，95%CI：0.82-0.91，P < 0.00001，I² = 66%）。多中心数据共纳入了四个胃癌队列，包含29,779名胃癌患者。女性胃癌患者的预后优于男性患者（HR = 0.938，95%CI：0.881-0.999，P = 0.046）。远端胃癌（Proximal Ref；Distal：HR = 0.815，95%CI：0.725-0.916，P = 0.001）、非印戒细胞癌（HR = 0.861，95%CI：0.770-0.962，P = 0.008）是女性患者的独立有利预后因素。吸烟史仅与女性患者群体生存率差相关（HR = 0.782，95%CI：0.616-0.993，P = 0.044）。在GEO数据库中，基于Hallmarker基因集的基因集富集分析（GSEA，the Gene Set Enrichment Analysis）结果显示，女性胃癌患者较健康女性的基因在免疫、肿瘤发生与雌激素反应相关通路中显著富集（P < 0.05）。

结论：本研究通过Meta分析和多中心数据分析发现，女性胃癌患者在临床病理特征及预后方面与男性患者存在显著差异。与男性患者相比较，女性胃癌患者占比相对较低，年龄更小，特定病理类型中占比较高，且预后相对较好。吸烟对女性胃癌患者的预后影响更为显著。此外，女性胃癌患者与健康女性的基因在雌激素反应相关通路中的富集程度存在差异。

Purpose: This study aims to explore the pathological and prognostic characteristics of gastric cancer in females, and to investigate the differences in clinical pathology and prognosis between female and male gastric cancer patients based on Meta-analysis and multi-center data. Finally, the molecular characteristics of female gastric cancer patients were further analyzed in order to provide reference for clinical treatment of gastric cancer. Materials and Methods: We systematically reviewed clinical studies from PubMed, Cochrane Library, Embase, and Web of Science published up to June 2022. Gastric cancer patients from four gastric cancer cohorts of the National Cancer Center of China, The First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Provincial Cancer Hospital between January 2000 and December 2020 were included in the study. Based on the Gene Expression Omnibus (GEO) database, gene expression profiles of female gastric cancer patients were constructed to compare differences between female gastric cancer patients and non-cancer controls. Results: The Meta-analysis included 76 articles and 775,003 gastric cancer patients. Results showed that females accounted for a smaller proportion of gastric cancer patients than males (Odds ratios [OR] = 0.27, 95% CI: 0.26-0.29, p < 0.00001, I² = 99%). Female patients were younger and had higher proportions in distal, non-cardia, undifferentiated, diffuse, and signet-ring cell carcinoma (all P < 0.00001). They also had better 3- and 5- year overall survival (OS) than males (Hazard ratio [HR] = 0.90, 95% Confidence interval [CI]: 0.86-0.95, P = 0.003, I² = 53%; HR = 0.86, 95% CI: 0.82-0.91, P < 0.00001, I² = 66%). Multi-center data from four cohorts with 29,779 patients found that female patients had a better prognosis (HR = 0.938, 95% CI: 0.881-0.999, P = 0.046). Distal gastric cancer (Proximal Ref; Distal: HR = 0.815, 95% CI: 0.725-0.916, P = 0.001) and non-signet-ring cell carcinoma (HR = 0.861, 95% CI: 0.770-0.962, P = 0.008) were independent favorable prognostic factors for female patients. Smoking history was only linked to worse survival in female patients (HR = 0.782, 95% CI: 0.616-0.993, P = 0.044). The results of the gene set enrichment analysis (GSEA) based on the Hallmarker gene sets revealed that female gastric cancer patients showed significant enrichment in immune response, tumorigenesis, and estrogen response pathways compared to non-cancer females (P < 0.05). Conclusion: This study, based on Meta-analysis and multi-center data analysis, found that female gastric cancer patients significantly differed from males in clinical pathological features and prognosis. They were fewer in number, younger, and more common in specific pathological types, while they had a better prognosis than males. Smoking history had a more pronounced impact on the prognosis of female gastric cancer patients. In addition, genes from female gastric cancer patients differed from non-tumor controls in their degree of enrichment in pathways related to estrogen response.