Lu Chenglu, Chen Shuai, Liu Shasha, Liu Huimin, Sun Lin, Sun Yan
Department of Pathology, National Clinical Research Centre for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Centre for Cancer, Tianjin Medical University Cancer Institute and Hospital, Huanhu West Road, Hexi District, Tianjin 300060, China.
Department of Pathology, Affiliated Hospital of Jining Medical University, Jining 272100, Shandong, China.
J Cancer. 2024 Jul 16;15(15):4838-4852. doi: 10.7150/jca.95622. eCollection 2024.
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. 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 assays to demonstrate the tumor suppressive effect of OTOP2 in COAD cells. OTOP2 expression was abnormal in multiple types of tumors and was significantly downregulated in patients with COAD (<0.001). Moreover, the presence of OTOP2 was linked to enhanced survival in individuals diagnosed with COAD. 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 (<0.001) as well as between OTOP2 expression and the number of effector cells (<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. 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.
耳钙黏蛋白2（OTOP2）是一种保守的离子通道蛋白，可调节细胞信号传导、生长和发育。尽管在多项结肠癌（COAD）研究中已报道了OTOP2在肿瘤抑制中的作用，但其对肿瘤的免疫调节作用尚未明确。我们使用来自癌症基因组图谱（TCGA）的数据，对COAD患者中OTOP2的表达及其与临床病理特征、免疫相关途径和免疫相关分子的关联进行了全面分析，并通过组织微阵列（TMA）证实了研究结果。我们进行了实验以证明OTOP2在COAD细胞中的肿瘤抑制作用。OTOP2在多种肿瘤类型中表达异常，在COAD患者中显著下调（<0.001）。此外，OTOP2的存在与COAD确诊患者的生存期延长有关。实验表明，OTOP2可抑制细胞增殖、迁移、侵袭和黏附。对TCGA数据库的基因集富集分析表明，OTOP2与抗原呈递途径和T细胞反应呈正相关。免疫表型评分（IPS）表明，OTOP2表达与MHC分子表达之间呈正相关（<0.001），OTOP2表达与效应细胞数量之间也呈正相关（<0.01）。TMA的免疫组织化学分析显示，COAD患者中OTOP2表达与MHC-I、TAP1和TAP2表达之间以及OTOP2表达与CD8 T细胞浸润之间存在强关联。总之，我们的研究强调了OTOP2作为肿瘤抑制因子的作用，表明其可作为COAD患者免疫治疗反应的预后指标和预测因子。
