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. 2022 Jun 1:12:913670.
doi: 10.3389/fonc.2022.913670. eCollection 2022.

CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer

Li Yuan  1   2   3 , Jingli Xu  4 , Yunfu Shi  4 , Zhiyuan Jin  1 , Zhehan Bao  4 , Pengcheng Yu  4 , Yi Wang  4 , Yuhang Xia  4 , Jiangjiang Qin  1   2   3 , Bo Zhang  5 , Qinghua Yao  5   6   7
Affiliations

CD3D Is an Independent Prognostic Factor and Correlates With Immune Infiltration in Gastric Cancer

Li Yuan et al. Front Oncol. .

Abstract

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 (P<0.000). Univariate and multivariate analyses showed that CD3D was an independent good prognostic factor for gastric cancer (P=0.004, HR=0.677, 95%CI: 0.510-0.898 for univariate analyses; P=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 (P=0.012 for tumor location; P=0.007 for Borrmann type; P=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 (P=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.

Keywords: PD-L1; cd3d; gastric cancer; prognosis; tumor infiltrating lymphocytes (TILs).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
CD3D is overexpressed in gastric cancer tissues compared with adjacent tissues, and a high expression of CD3D is associated with a good prognosis in gastric cancer patients. (A) Representative images of CD3D staining in TMAs as determined by immunohistochemical analysis. (B) Differential expression of CD3D in gastric cancer tissue and paracancerous tissue. (C) The overall survival (OS) curves of gastric cancer patients with different CD3D expression levels in tumor tissues as determined by Kaplan–Meier analysis (log-rank test). (D) The OS curves of gastric cancer patients with different CD3D expression levels in paracancerous tissues as determined by Kaplan–Meier analysis (log-rank test). ***p < 0.001.
Figure 2
Figure 2
Tumor infiltrating lymphocytes (TILs) and PD-L1 are closely related to the prognosis of gastric cancer. Representative images of CD3 (A), CD4 (C), CD8 (E), and PD-L1 (G) staining in TMAs as determined by immunohistochemical analysis. The overall survival (OS) curves of gastric cancer patients with different CD3 (B), CD4 (D), CD8 (F), and PD-L1 (H) expression levels in tumor tissues as determined by Kaplan–Meier analysis (log-rank test).
Figure 3
Figure 3
The expression of CD3D is highly positively correlated with the expression of CD3, CD4, CD8, and PD-L1. (A) The relationship between the expression of CD3D and CD3. (B) The relationship between the expression of CD3D and CD4. (C) The relationship between the expression of CD3D and CD8. (D) Relationship between the expression of CD3D and PD-L1. ***p < 0.001.
Figure 4
Figure 4
CD3Dhigh combined with CD4high, CD8high and PD-L1- predicts the best prognosis of gastric cancer. (A) The overall survival (OS) curves of gastric cancer patients with different CD3D combined with CD3 expression levels in tumor tissues. (B) The OS curves of gastric cancer patients with different CD3D and CD4 expression levels in tumor tissues. (C) The OS curves of gastric cancer patients with different CD3D and CD8 expression levels in tumor tissues. (D) The OS curves of gastric cancer patients with different CD3D combined with PD-L1 expression levels in tumor tissues. (E) The OS curves of gastric cancer patients with different CD3D, CD4 and CD8 expression levels in tumor tissues. (F) The OS curves of gastric cancer patients with different CD3D, CD4, CD8 and CD3 expression levels in tumor tissues. (G) The OS curves of gastric cancer patients with different CD3D, CD4, CD8 and PD-L1 expression levels in tumor tissues. (H) The OS curves of gastric cancer patients with different CD3D, CD4, CD8, CD3 and PD-L1 expression levels in tumor tissues. E-H: Because of the large number of groups, we only show some groups with large number of cases.
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