Gastric cancer (GC) poses a significant health challenge worldwide, necessitating the identification of predictive biomarkers to improve prognosis. Dysregulated lipid metabolism is a well-recognized hallmark of tumorigenesis, prompting investigation into apolipoproteins (APOs). In this study, we focused on apolipoprotein D (APOD) following comprehensive analyses of APOs in pan-cancer. Utilizing data from the TCGA-STAD and GSE62254 cohorts, we elucidated associations between APOD expression and multiple facets of GC, including prognosis, tumor microenvironment (TME), cancer biomarkers, mutations, and immunotherapy response, and identified potential anti-GC drugs. Single-cell analyses and immunohistochemical staining confirmed APOD expression in fibroblasts within the GC microenvironment. Additionally, we independently validated the prognostic significance of APOD in the ZN-GC cohort. Our comprehensive analyses revealed that high APOD expression in GC patients was notably associated with unfavorable clinical outcomes, reduced microsatellite instability and tumor mutation burden, alterations in the TME, and diminished response to immunotherapy. These findings provide valuable insights into the potential prognostic and therapeutic implications of APOD in GC.

中文翻译：

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揭示 APOD 作为胃癌生物标志物的潜力：一项回顾性多中心研究

胃癌（GC）在全世界范围内构成了重大的健康挑战，因此需要鉴定预测性生物标志物以改善预后。脂质代谢失调是肿瘤发生的一个公认标志，促使人们对载脂蛋白（APO）进行研究。在本研究中，我们在对泛癌中的 APO 进行全面分析后，重点关注载脂蛋白 D (APOD)。利用 TCGA-STAD 和 GSE62254 队列的数据，我们阐明了 APOD 表达与 GC 多个方面之间的关联，包括预后、肿瘤微环境 (TME)、癌症生物标志物、突变和免疫治疗反应，并确定了潜在的抗 GC 药物。单细胞分析和免疫组织化学染色证实了 GC 微环境中成纤维细胞中的 APOD 表达。此外，我们独立验证了 ZN-GC 队列中 APOD 的预后意义。我们的综合分析显示，GC 患者中 APOD 高表达与不良临床结果、微卫星不稳定性和肿瘤突变负担减少、TME 改变以及免疫治疗反应减弱显着相关。这些发现为 APOD 在 GC 中的潜在预后和治疗意义提供了宝贵的见解。