Background: Human aldo-keto reductase family 1 member C3 (AKR1C3) is an important molecule that participates in multiple physiological metabolic processes. However, its expression, biological functions and clinical significance in gastric carcinogenesis are unclear./nMethods: We collected data from several public data portals and clinical samples and systematically analyzed the clinical significance of tissue and plasma AKR1C3 expression. Then, we filtered prognostic risk factors and established novel prognosis-related nomogram models for predicting overall survival time and postoperative recurrence risk. The application value of the nomogram models was further assessed using clinical samples. Moreover, we explored the potential biological functions of AKR1C3 in gastric carcinogenesis and metastasis through multiomics functional analysis and immune infiltration analysis./nResults: AKR1C3 levels were reduced in cancer tissue but increased significantly in the plasma of GC patients; AKR1C3 expression in either sample type was closely associated with multiple clinicopathological characteristics. By combining clinicopathological factors and AKR1C3 levels, two novel nomogram models were developed to predict overall survival time and postoperative recurrence risk. Multiomics functional analysis revealed that when its expression is dysregulated, AKR1C3 can widely participate in gene expression regulation through multiple regulatory modes at the gene, RNA and protein levels and exert various crucial biological effects in carcinogenesis and metastasis. Moreover, AKR1C3 expression was correlated with the infiltration of several immune cell types, and AKR1C3 was predicted to interact with several clinical drugs./nConclusion: Dysregulated AKR1C3 expression is related to gastric carcinogenesis and immunotherapy response and is a promising biomarker and effective biotherapy target in GC.

中文翻译：

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通过多组学功能分析和免疫浸润分析明确AKR1C3在胃癌发生中的生物学功能和临床意义

背景：人醛酮还原酶家族1成员C3（AKR1C3）是参与多种生理代谢过程的重要分子。然而，其表达、生物学功能以及在胃癌发生中的临床意义尚不清楚。/n方法：我们从多个公共数据门户和临床样本收集数据，系统分析组织和血浆AKR1C3表达的临床意义。然后，我们筛选了预后风险因素，并建立了新的预后相关列线图模型，用于预测总生存时间和术后复发风险。使用临床样本进一步评估列线图模型的应用价值。此外，我们通过多组学功能分析和免疫浸润分析探讨了AKR1C3在胃癌发生和转移中的潜在生物学功能。/n结果： AKR1C3在胃癌组织中水平降低，但在胃癌患者血浆中显着升高；任一样本类型中的 AKR1C3 表达与多种临床病理特征密切相关。通过结合临床病理因素和 AKR1C3 水平，开发了两种新型列线图模型来预测总生存时间和术后复发风险。多组学功能分析表明，当其表达失调时，AKR1C3可以通过基因、RNA和蛋白质水平的多种调控模式广泛参与基因表达调控，并在癌变和转移中发挥多种关键的生物学作用。此外，AKR1C3 表达与多种免疫细胞类型的浸润相关，并且 AKR1C3 预计与多种临床药物相互作用。/n结论：AKR1C3 表达失调与胃癌发生和免疫治疗反应相关，是一种有前途的生物标志物和有效的生物治疗靶点在气相色谱中。