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

Li, Yuan; Xu, Jingli; Shi, Yunfu; Jin, Zhiyuan; Bao, Zhehan; Yu, Pengcheng; Wang, Yi; Xia, Yuhang; Qin, Jiang‐Jiang; Zhang, Bo; Yao, Qinghua

doi:10.3389/fonc.2022.913670

Cited by 10 publications

(11 citation statements)

References 41 publications

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“…The results presented that CD3D expression was associated with the four immune cells, IRF1 and CCL3 expression with the five immune cells, and FN1 only with three immune cells (Figure 4F–V). In addition, DNA methylation of CD3D in breast, bladder, and gastric cancers has been reported 23–25 . Our study also found that CD3D gene expression had the highest correlation with its methylation level in UM.…”

Section: Resultssupporting

confidence: 69%

“…Epigenetic regulation is a major factor in driving transcriptional activation of an array of genes that are essential for immunity in cancer, including T cell receptor genes (for instance, CD3D); a high adverse correlation between the promoter CpG methylation and CD3D expression has been detected in renal and thyroid cancers 40 . Previous results showed highly expressed CD3D in gastric cancer tissues compared with paracancerous tissues and positively correlated with immune infiltration in gastric cancer 23 . Furthermore, CD3D has an intensive correlation with CD8 + T cells, and its upregulation can increase T cell immune infiltration in the tumor microenvironment and induce antitumor immunity by activating T lymphocytes in breast carcinoma 44 .…”

Section: Discussionmentioning

confidence: 99%

“…40 Previous results showed highly expressed CD3D in gastric cancer tissues compared with paracancerous tissues and positively correlated with immune infiltration in gastric cancer. 23 Furthermore, CD3D has an intensive correlation with CD8 + T cells, and its upregulation can increase T cell immune infiltration in the tumor microenvironment and induce antitumor immunity by activating T lymphocytes in breast carcinoma. 44 The present study represents the first report to reveal the augmented expression of CD3D in UM and its positive association with immune infiltration and the malignant phenotype cancer cells in UM.…”

Section: Discussionmentioning

confidence: 99%

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Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma

Zhang,

2023

The FASEB Journal

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Alterations in DNA methylation in malignant diseases have been heralded as promising targets for diagnostic, prognostic, and predictive values. This study was based on epigenetic alterations and immune cell infiltration analysis to investigate the mechanism of CD3D methylation in uveal melanoma (UM). Bioinformatics analysis was performed on transcriptome data, 450 K methylation data, and clinical information of UM patients from the TCGA database. Stromal and immune cell infiltration was evaluated by calculating the StromalScore and ImmuneScore of UM samples. UM samples were divided into high and low StromalScore and ImmuneScore groups, followed by differential and enrichment analyses. PPI network construction and correlation analysis was used to identify the core prognosis‐related genes. The bioinformatics analysis results were confirmed in UM cell experiments. StromalScore and ImmuneScore were significantly associated with the prognosis of UM patients. CD3D, IRF1, CCL3, and FN1 were identified as core genes driven by methylation that affected the prognosis of UM patients. CD3D expression showed the highest correlation with its methylation and was closely related to the four key immune cells in UM development. CD3D was hypomethylated and abundantly expressed in UM cells, while silencing of CD3D inhibited the proliferation, migration, and invasion of UM cells in vitro. In summary, this study identifies hypomethylation of CD3D promoter in UM, which was associated with immune cell infiltration of UM.

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Section: Resultssupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma

Zhang,

2023

The FASEB Journal

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“…Previous studies have shown that CD3D may serve as a prognostic maker of colon cancer, gastric cancer and other tumors ( 33 , 34 ); CD3E can be used as a prognostic factor of lung cancer ( 35 ); the expression of CD247 was associated with many cancers, including gastric cancer, head and neck cancer and ovarian cancer ( 36 – 38 ). Very few studies mentioned that CD3G was related to the initiation of CESC or the other cancer types.…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic biomarker CD3G that correlates with the tumor microenvironment in cervical cancer

Wang

Cao

et al. 2022

Front. Oncol.

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Cervical cancer (CESC) is the fourth most common and death-causing gynecological cancer, mostly induced by infection of human papillomavirus (HPV). Multiple components of the tumor microenvironment (TME), such as tumor infiltrating immune cells, could be targets of immunotherapy for HPV-related CESC. However, little is known about the TME of CESC until now. Here, we aimed to uncover the pathogenesis as well as to identify novel biomarkers to predict prognosis and immunotherapy efficacy for CESC. Combining the transcriptomic data and clinical characteristics, we identified differentially expressed genes in CESC samples from TCGA database by comparing the two groups with different ImmuneScore and StromalScore. Next, we detected ten key genes based on the PPI network and survival analyses with the univariate Cox regression model. Thereafter, we focused on CD3G, the only gene exhibiting increased RNA and protein expression in tumors by multiple analyses. Higher CD3G expression was associated with better survival; and it was also significantly associated with immune-related pathways through GSEA analysis. Furthermore, we found that CD3G expression was correlated with 16 types of TICs. Single cell RNA-sequencing data of CD3G in lymphocytes subgroup indicated its possible role in HPV defense. Hence, CD3G might be a novel biomarker in prognosis and immunotherapy for CESC patients.

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“…Furthermore, a correlation was also observed between ERCC1 expression and HRD, thus suggesting that ERCC1 expression could also reduce the efficacy of chemotherapeutic drugs like cisplatin and carboplatin. T cells play an important role in cancer, CD3 is an important T cells biomarker, and CD3 deficiency of CD3 could lead to severe combined immunodeficiency ( 21 , 22 ). CD206 is an important biomarker of M2 macrophages.…”

Section: Discussionmentioning

confidence: 99%

ERCC1 is a potential biomarker for predicting prognosis, immunotherapy, chemotherapy efficacy, and expression validation in HER2 over-expressing breast cancer

Liao²,

Ma³

2022

Front. Oncol.

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ObjectiveTo investigate the relationship between Excision repair cross-complementation 1 (ERCC1) expression, clinicopathological features, and breast cancer prognosis in patients treated with trastuzumab. Further, we aim to explore the immune status of ERCC1 in breast cancer.MethodsThe data were retrieved from publicly available databases like the Cancer Genome Atlas, Therapeutically Applicable Research to Generate Effective Treatments, and the Genotype-Tissue Expression. The data was used to perform differential expression analyses between tumor and normal tissues in pan-cancers, immune-related analysis, homologous recombination deficiency (HRD), tumor mutation burden, and microsatellite instability. A total of 210 patients with HER2 over-expressing breast cancer from the Fourth Hospital of Hebei Medical University between January 2013 to December 2015 were enrolled in the study. Ten adjacent normal tissues were used to study the expression pattern of ERCC1 in normal tissues. Immunohistochemistry was performed to study ERCC1 expression and immune cell infiltration in different status of ERCC1 expression. Further, the correlation between ERCC1 expression, immune cell infiltration clinicopathological features, and the prognosis of patients with breast cancer was analyzed.ResultsThe immune analysis revealed a significant correlation between CD8+ T cell, CD4+ T cell, T helper cell, macrophages, mast cells, and ERCC1 expression. Spearman analysis show that ERCC1 expression is related to macrophages and T cells. A close correlation was observed between increased ERCC1 expression and high tumor immune dysfunction and exclusion (TIDE) score as well as HRD. The results revealed a significant correlation among ERCC1, chemotherapy and estrogen receptor (ER; P < 0.05) expression. Univariate survival analysis revealed a significant correlation (P < 0.05) between that ERCC1 and ER expression, blood vessel invasion, and disease-free survival (DFS). ERCC1 and ER expression, tumor size, blood vessel invasion, pathological type, and lymph node metastases significantly correlated (P < 0.05) with overall survival in patients. Multivariate regression analysis revealed that ERCC1 expression and chemotherapy were independent factors that influence DFS. ERCC1 expression and vascular tumor thrombus were independent influencing factors that influence OS.ConclusionA correlation was observed between high ERCC1 expression and poor patient prognosis. High ERCC1 expression also influences the efficacy of immunotherapy and chemotherapy.

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

Cited by 10 publications

References 41 publications

Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma

Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma

A novel prognostic biomarker CD3G that correlates with the tumor microenvironment in cervical cancer

ERCC1 is a potential biomarker for predicting prognosis, immunotherapy, chemotherapy efficacy, and expression validation in HER2 over-expressing breast cancer

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