Bioinformatics analysis and experiments identify CD74 as a potential immune target in ovarian carcinoma
Bioinformatics analysis and experiments identify CD74 as a potential immune target in ovarian carcinoma
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生物信息学分析和实验确定 CD74 是卵巢癌的潜在免疫靶点
DOI：
10.5114/aoms/155116
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发表时间：
2022-10
影响因子：
3.8
通讯作者：
li feng
中科院分区：
文献类型：
--
作者：
yixin zhang;xinhui zhang;li zhang;yuli zhao;sen wang;li feng
卵巢癌（OC）是世界范围内女性最常见的恶性肿瘤之一。免疫检查点抑制剂通常用于治疗OC，但临床成功率很低。在这里，我们旨在探索用于OC管理的新型免疫有效生物标志物。数据集来自癌症基因组图谱，基因型-组织表达，和临床蛋白质组学肿瘤分析联盟用于鉴定与CD 8+显著相关的枢纽基因。T效应子和免疫检查点特征，并探讨CD 74在OC中的潜在致癌作用。免疫检查点构建抑制因子评分（IMS）用免疫组化方法进一步验证了CD 74在OC组织中的表达。黄色基因模块显示，与CD 8 + T效应子和免疫检查点谱显著相关。功能富集分析表明，黄色基因模块与免疫应答和抗原结合相关。因此，IMS可以准确预测免疫治疗反应性和预后。此外，CD 74在OC中在mRNA和蛋白水平均显著上调，CD 74蛋白的高表达与多种肿瘤相关通路的激活有关。Kaplan-Meier分析显示，CD 74高表达与OC预后不良相关，CD 74表达与炎性细胞因子、免疫细胞、肿瘤免疫微环境及免疫检查点密切相关。CD 74可能代表一种新的预测OC患者预后的免疫生物标志物，也可能成为免疫治疗相关的潜在治疗靶点，为OC的治疗提供新的思路。
Ovarian carcinoma (OC) is one of the most common malignancies in women worldwide.Immune checkpoint inhibitors are routinely used to treat OC, but with little clinical success.Here,we aimed to explore novel immune-effective biomarkers for OC management.Datasets from The Cancer Genome Atlas,Genotype-Tissue Expression, and the Clinical Proteomic Tumor Analysis Consortium were used to identify hub genes significantly associated with CD8+ T effectors and immune checkpoint signatures and to explore the potential oncogenic role of CD74 in OC.The immune checkpoint construct inhibitor score (IMS) was constructed to predict immunotherapy responsiveness and prognosis.CD74 expression was further validated using immunohistochemistry in OC tissues.The yellow gene module showed a significant correlation with the CD8+ T effector and immune checkpoint profiles.Functional enrichment analysis showed that the yellow gene module was associated with immune response and antigen binding.Thus, IMS can accurately predict immunotherapy responsiveness and prognosis.In addition,CD74 was significantly upregulated at both the mRNA and protein levels in OC, and the high expression of the CD74 protein was related to the activation of various tumor-related pathways. Kaplan-Meier analysis showed that high CD74 expression correlated with poor prognosis in OC.Furthermore,CD74 expression remarkably correlated with inflammatory cytokines,immune cells,the tumor immune microenvironment, and immune checkpoints.Finally,CD74 expression in pericarcinomatous and cancer tissues from OC patients was verified via IHC analysis,which corresponded to the public database results (all p < 0.05).CD74 may represent a novel immune biomarker to predict the prognosis of OC patients,as well as a potential therapeutic target related to immunotherapy,providing new ideas for the treatment of OC.