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Abstract：
Background: CD161 has been identified as a prognostic biomarker in many neoplasms, but its role in breast cancer (BC) has not been fully explained. We aimed to investigate the molecular mechanism and prognostic value of CD161 in BC. Methods: CD161 expression profile was extracted from TIMER, Oncomine, UALCAN databases, and verified by the Gene Expression Omnibus (GEO) database and quantitative real-time polymerase chain reaction (qRT-PCR). The prognostic value of CD161 was assessed via GEPIA, Kaplan-Meier plotter and PrognoScan databases. The Cox regression and nomogram analyses were conducted to further validate the association between CD161 expression and survival. Gene set enrichment analysis (GSEA), Gene Ontology (GO) analysis, and KEGG pathway enrichment analysis were performed to probe the tumor-associated annotations of CD161. CIBERSORT and ssGSEA were employed to investigate the correlation between CD161 expression and immune cell infiltration in BC, and the result was verified by TIMER and TISIDB. Results: Multiple BC cohorts showed that CD161 expression was decreased in BC, and a high CD161 expression was associated with a preferable prognosis. Therefore, we identified the combined model including CD161, age and PR status to predict the survival (C index = 0.78) of BC patients. Functional enrichment analysis indicated that CD161 and its co-expressed genes were closely related to several cancerous and immune signaling pathways, suggesting its involvement in immune response during cancer development. Moreover, immune infiltration analysis revealed that CD161 expression was correlated with immune infiltration. Conclusion: Collectively, our findings revealed that CD161 may serve as a potential biomarker for favorable prognosis and a promising immune therapeutic target in BC.
摘要：
背景：CD161已被确定为许多肿瘤的预后生物标志物，但其在乳腺癌（BC）中的作用尚未得到充分解释。我们旨在探讨CD161在BC中的分子机制和预后价值。方法：从TIMER中提取CD161表达谱，Oncomine,UALCAN数据库,并通过基因表达综合（GEO）数据库和定量实时聚合酶链反应（qRT-PCR）验证。通过GEPIA评估CD161的预后价值，Kaplan-Meier绘图仪和PrognoScan数据库。进行Cox回归和列线图分析以进一步验证CD161表达和生存之间的关联。基因集富集分析(GSEA),基因本体论（GO）分析，和KEGG途径富集分析以探测CD161的肿瘤相关注释。采用CIBERSORT和ssGSEA研究BC中CD161表达与免疫细胞浸润的相关性。并通过TIMER和TISIDB对结果进行了验证。结果：多个BC队列显示BC中CD161表达降低，CD161的高表达与较好的预后相关。因此,我们确定了包括CD161,年龄和PR状态的组合模型来预测BC患者的生存率(C指数=0.78).功能富集分析表明,CD161及其共表达基因与几种癌变和免疫信号通路密切相关,提示其参与癌症发展过程中的免疫反应。此外，免疫浸润分析显示CD161的表达与免疫浸润有关。结论：集体，我们的研究结果表明,CD161可能是BC预后良好的潜在生物标志物和有前景的免疫治疗靶点.
