Shi Wen-Qi, Chen Dan-Xun, Du Ze-Sen, Liu Chun-Peng, Zhai Tian-Tian, Pan Feng, Chen Hai-Lu, Liao Wei-Nan, Wang Shao-Hong, Fu Jun-Hui, Qiu Si-Qi, Wu Zhi-Yong
Clinical Research Center, Shantou Central Hospital, Shantou, 515041, China.
Diagnosis and Treatment Center of Breast Diseases, Shantou Central Hospital, Shantou, 515041, China.
Cancer Cell Int. 2024 Oct 14;24(1):340. doi: 10.1186/s12935-024-03524-w.
Immune checkpoint blockade (ICB) has been improving the patient outcome in multiple cancer types. However, not all patients respond to ICB. Biomarkers are needed for selecting appropriate patients to receive ICB. CD74 is an important chaperone that regulates antigen presentation for immune response. However, the relationship between CD74 expression and ICB response remains elusive.
The unified normalized pan-cancer dataset was downloaded from the UCSC database. Wilcoxon Rank Sum Rank Tests were used to analyze the expression differences between normal and tumor samples in each tumor type. Then, the prognostic value of CD74 was determined using univariable Cox proportional hazards regression analysis. The STRING database was utilized to construct the protein-protein interaction (PPI) network of CD74 and the signal pathways were analyzed as well. The correlation of CD74 expression with immune cells and immune regulating genes was investigated in the TIMER database. The TIDE framework was utilized to evaluate the relationship between CD74 expression and the response to immunotherapy. Moreover, the localization of CD74 in the tumor immune microenvironment was verified using multiplex immunohistochemistry. Clinically annotated samples from 38 patients with esophageal cancer treated with neoadjuvant chemotherapy combined with ICB were analyzed for CD74 expression using immunohistochemistry.
In this study, we investigated the prognostic and predictive value of CD74 in different types of cancer. Compared with normal tissue, the expression of CD74 was higher in tumor tissue in various cancers. High expression of CD74 was associated with improved patient prognosis in the majority of cancers. CD74 and its interacting proteins were mainly enriched in the immune-related pathways. The expression of CD74 was significantly positively correlated with B cells, CD4 T-cells, CD8 T-cells, neutrophils, macrophages and dendritic cells. TIDE analysis showed that tumors with high CD74 expression may have better responses to immunotherapy and improved patient survival. In patients with esophageal cancer who had received ICB, higher intratumoral CD74 expression was associated with improved response to ICB.
The findings of this study suggest that the high expression of CD74 may be a potential predictive biomarker of response to ICB.
免疫检查点阻断（ICB）已改善多种癌症类型患者的预后。然而，并非所有患者都对ICB有反应。需要生物标志物来选择合适的患者接受ICB治疗。CD74是一种重要的伴侣蛋白，可调节免疫反应的抗原呈递。然而，CD74表达与ICB反应之间的关系仍不明确。
从UCSC数据库下载统一标准化的泛癌数据集。使用Wilcoxon秩和检验分析每种肿瘤类型中正常样本与肿瘤样本之间的表达差异。然后，使用单变量Cox比例风险回归分析确定CD74的预后价值。利用STRING数据库构建CD74的蛋白质-蛋白质相互作用（PPI）网络，并分析信号通路。在TIMER数据库中研究CD74表达与免疫细胞和免疫调节基因的相关性。利用TIDE框架评估CD74表达与免疫治疗反应之间的关系。此外，使用多重免疫组织化学验证CD74在肿瘤免疫微环境中的定位。对38例接受新辅助化疗联合ICB治疗的食管癌患者的临床注释样本进行免疫组织化学分析，以检测CD74表达。
在本研究中，我们研究了CD74在不同类型癌症中的预后和预测价值。与正常组织相比，CD74在各种癌症的肿瘤组织中表达更高。在大多数癌症中，CD74的高表达与患者预后改善相关。CD74及其相互作用蛋白主要富集于免疫相关通路。CD74的表达与B细胞、CD4 T细胞、CD8 T细胞、中性粒细胞、巨噬细胞和树突状细胞显著正相关。TIDE分析表明，CD74高表达的肿瘤可能对免疫治疗有更好的反应，并改善患者生存。在接受ICB治疗的食管癌患者中，肿瘤内CD74表达较高与对ICB的反应改善相关。
本研究结果表明，CD74的高表达可能是ICB反应的潜在预测生物标志物。
