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Abstract：
Background: Otopetrin 2 (OTOP2) is a conserved ion channel protein that regulates cell signaling, growth, and development. Although the role of OTOP2 in tumor suppression has been reported in several studies of colon adenocarcinoma (COAD), characterized its immunomodulatory effects on tumors. Methods: We conducted a thorough analysis of OTOP2 expression and its association with clinicopathological characteristics, immune-related pathways, and immune-related molecules in individuals with COAD using data from The Cancer Genome Atlas (TCGA) and confirmed the findings with tissue microarrays (TMAs). We conducted in vitro assays to demonstrate the tumor suppressive effect of OTOP2 in COAD cells. Results: OTOP2 expression was abnormal in multiple types of tumors and was significantly downregulated in patients with COAD (P<0.001). Moreover, the presence of OTOP2 was linked to enhanced survival in individuals diagnosed with COAD. In vitro experiments showed that OTOP2 suppressed cell proliferation, migration, invasion, and adhesion. Gene set enrichment analysis of the TCGA database indicated that OTOP2 was positively correlated with antigen presentation pathways and T cell responses. The immunophenoscore (IPS) indicated a positive correlation between OTOP2 expression and MHC molecule expression (P<0.001) as well as between OTOP2 expression and the number of effector cells (P<0.01). Immunohistochemical analysis of the TMAs revealed strong associations between OTOP2 expression and MHC-I, TAP1, and TAP2 expression, and between OTOP2 expression and CD8+ T cell infiltration in COAD patients. Conclusion: In summary, our research emphasizes the role of OTOP2 as a tumor suppressor, suggesting its use as a prognostic indicator and predictor of response to immunotherapy in COAD patients.
摘要：
背景：Otopetrin2（OTOP2）是一种保守的离子通道蛋白，可调节细胞信号传导，增长,和发展。尽管在结肠腺癌（COAD）的一些研究中已经报道了OTOP2在肿瘤抑制中的作用，其特点是对肿瘤的免疫调节作用。方法：我们对OTOP2的表达及其与临床病理特征的关系进行了全面分析，免疫相关途径，使用来自癌症基因组图谱（TCGA）的数据，并通过组织微阵列（TMA）证实了该发现。我们进行了体外测定以证明OTOP2在COAD细胞中的肿瘤抑制作用。结果：OTOP2在多种肿瘤中表达异常，在COAD患者中表达明显下调（P<0.001）。此外，OTOP2的存在与COAD诊断患者的生存率提高相关.体外实验表明OTOP2抑制细胞增殖,迁移,入侵,和附着力。TCGA数据库的基因集富集分析表明OTOP2与抗原呈递途径和T细胞应答呈正相关。免疫表型（IPS）表明OTOP2表达与MHC分子表达呈正相关（P<0.001），OTOP2表达与效应细胞数量呈正相关（P<0.01）。TMA的免疫组织化学分析显示OTOP2表达与MHC-I之间有很强的关联，TAP1和TAP2表达，COAD患者OTOP2表达与CD8+T细胞浸润之间的关系。结论：总之，我们的研究强调了OTOP2作为肿瘤抑制因子的作用，提示其用作COAD患者免疫治疗反应的预后指标和预测指标。
