Yuan Li, Xu Jingli, Shi Yunfu, Jin Zhiyuan, Bao Zhehan, Yu Pengcheng, Wang Yi, Xia Yuhang, Qin Jiangjiang, Zhang Bo, Yao Qinghua
The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, China.
Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital, Hangzhou, China.
Front Oncol. 2022 Jun 1;12:913670. doi: 10.3389/fonc.2022.913670. eCollection 2022.
The protein encoded by CD3D is part of the T-cell receptor/CD3 complex (TCR/CD3 complex) and is involved in T-cell development and signal transduction. Previous studies have shown that CD3D is associated with prognosis and treatment response in breast, colorectal, and liver cancer. However, the expression and clinical significance of CD3D in gastric cancer are not clear. In this study, we collected 488 gastric cancer tissues and 430 paired adjacent tissues to perform tissue microarrays (TMAs). Then, immunohistochemical staining of CD3D, CD3, CD4, CD8 and PD-L1 was conducted to investigate the expression of CD3D in gastric cancer and the correlation between the expression of CD3D and tumor infiltrating lymphocytes (TILs) and PD-L1. The results showed that CD3D was highly expressed in gastric cancer tissues compared with paracancerous tissues (<0.000). Univariate and multivariate analyses showed that CD3D was an independent good prognostic factor for gastric cancer (=0.004, HR=0.677, 95%CI: 0.510-0.898 for univariate analyses; =0.046, HR=0.687, 95%CI: 0.474-0.994 for multivariate analyses). In addition, CD3D was negatively correlated with the tumor location, Borrmann type and distant metastasis (=0.012 for tumor location; =0.007 for Borrmann type; =0.027 for distant metastasis). In addition, the expression of CD3D was highly positively correlated with the expression of CD3, CD4, CD8, and PD-L1, and the combination of CD3D with CD3, CD4, CD8 and PD-L1 predicted the best prognosis (=0.043). In summary, CD3D may play an important regulatory role in the tumor immune microenvironment of gastric cancer and may serve as a potential indicator of prognosis and immunotherapy response.
CD3D编码的蛋白质是T细胞受体/CD3复合物（TCR/CD3复合物）的一部分，参与T细胞发育和信号转导。先前的研究表明，CD3D与乳腺癌、结直肠癌和肝癌的预后及治疗反应相关。然而，CD3D在胃癌中的表达及临床意义尚不清楚。在本研究中，我们收集了488例胃癌组织和430例配对的癌旁组织制作组织芯片（TMAs）。然后，进行CD3D、CD3、CD4、CD8和PD-L1的免疫组化染色，以研究CD3D在胃癌中的表达以及CD3D表达与肿瘤浸润淋巴细胞（TILs）和PD-L1之间的相关性。结果显示，与癌旁组织相比，CD3D在胃癌组织中高表达（<0.000）。单因素和多因素分析表明，CD3D是胃癌的独立良好预后因素（单因素分析：=0.004，HR=0.677，95%CI：0.510-0.898；多因素分析：=0.046，HR=0.687，95%CI：0.474-0.994）。此外，CD3D与肿瘤位置、Borrmann分型和远处转移呈负相关（肿瘤位置：=0.012；Borrmann分型：=0.007；远处转移：=0.027）。另外，CD3D的表达与CD3、CD4、CD8和PD-L1的表达呈高度正相关，且CD3D与CD3、CD4、CD8和PD-L1联合预测的预后最佳（=0.043）。总之，CD3D可能在胃癌的肿瘤免疫微环境中发挥重要调节作用，并可能作为预后和免疫治疗反应的潜在指标。
