The Role of CD276 in Cancers

Liu, Shengzhuo; Liang, Jiayu; Liu, Zhihong; Zhang, Chi; Wang, Yan; Watson, Alice Helen; Zhou, Chuan; Zhang, Fan; Wu, Kan; Lu, Yiping; Wang, Xianding

doi:10.3389/fonc.2021.654684

Cited by 74 publications

(72 citation statements)

References 86 publications

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“…Previous studies have consistently reported CENP-U to be positively correlated with HMGB2 in OV (24), and it has been shown that knockdown of CENP-U expression in bladder cancer can decrease the expression of HMGB1 (22). Among other immune checkpoints, (I) the PD-1 and PD-L1 axis was shown to act as a mechanism of tumor cell escape from host immunity (38), (II) LAG3 was reported to exert a suppressive effect on activated T cells (39), (III) VEGFA was found to inhibit the trafficking of cytotoxic T lymphocyte (CTL) and the maturation of DCs ( 40), (IV) CD276 was recently identified as a T cell inhibitor (41), and (V) CXCL9 and CXCL10 were demonstrated to promote the differentiation of naïve T cells to T helper (Th) cells (42); however, (VI) the effect of other immune checkpoints remains relatively controversial. From the abovementioned results, we can surmise that, compared with immune stimulators correlated to CENP-U expression, the immune inhibitors with correlations had a more profound effect on tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Shao¹,

Wang²,

Duan³

et al. 2021

Ann Transl Med

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Background: Centromere protein U (CENP-U) is a component of the kinetochore and can regulate the cell cycle as a receptor of polo-like kinase 1 (PLK1). Recent studies have partially identified the role of CENP-U in tumor progression, but the underlying mechanisms of CENP-U in tumor immunity remain obscure. Methods: We performed pan-cancer analysis to evaluate the role of CENP-U in immunity and proliferation with data from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE) datasets, and Genotype-Tissue Expression (GTEx) project. Results of CENP-U expression and related clinicopathological data were obtained to show the expression levels, prognosis, tumor progression, immune neoantigens, and immune checkpoints of CENP-U in 33 tumors. The Tumor Immune Estimation Resource (TIMER) dataset was used to analyze immune infiltration scores.Results: Results of the pan-cancer analysis demonstrated that CENP-U is differentially expressed in normal tissues and common tumor tissues. Moreover, differentially expressed CENP-U was also identified between matched normal and tumor tissues, and the high expression level of CENP-U was associated with poor prognosis for 33 kinds of tumor except for that of thymoma (THYM) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC). Furthermore, the correlation between CENP-U expression and immune checkpoints and immune neoantigens was determined. In addition, CENP-U expression was correlated with tumor-infiltrating immune cells especially in THYM but not in lung squamous cell carcinoma (LUSC), esophageal carcinoma (ESCA), or lung adenocarcinoma (LUAD). Finally, gene set enrichment analysis (GSEA) indicated that CENP-U is critically involved in tumor proliferation, immunity, and metabolism.Conclusions: CENP-U, a mitosis-related kinase, was found to be differentially expressed across different cancer types and to play an important role in tumor progression and immunity. CENP-U holds the potential to be a prognostic marker, whose targeting may provide therapeutic benefit.

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Section: Discussionmentioning

confidence: 99%

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Shao¹,

Wang²,

Duan³

et al. 2021

Ann Transl Med

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“…Notably, the expression of CTHRC1 was positively correlated with ICP gene CD276, which was identified a promising therapeutic target for malignant tumors (Additional file 10 : Fig. S10d) [ 64 ]. These results may indicate the underlying mechanisms for CTHRC1 regulation of immune cell function in tumors.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis combined with experiments predicts CTHRC1 as a therapeutic target for human cancers

et al. 2021

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Background The function of collagen triple helix repeat containing 1 (CTHRC1) as an oncogene has been reported in a growing number of publications. Bioinformatics methods represent a beneficial approach to examine the mechanism and function of the CTHRC1 gene in the disease process of cancers from a pan-cancer perspective. Methods In this study, using the online databases UCSC, NCBI, HPA, TIMER2, Oncomine, GEPIA, UALCAN, cBioPortal, COSMIC, MEXPRESS, STRING, CCLE, LinkedOmics, GTEx, TCGA, CGGA, and SangerBox, we focused on the relationship between CTHRC1 and tumorigenesis, progression, methylation, immunity, and prognosis. qPCR was used to detect CTHRC1 expression in glioma tissues and cell lines. Results The pan-cancer analysis showed that CTHRC1 was overexpressed in most tumors, and a significant correlation was observed between CTHRC1 expression and the prognosis of patients with cancer. CTHRC1 genetic alterations occur in diverse tumors and are associated with tumor progression. Levels of CTHRC1 promoter methylation were decreased in most cancer tissues compared with normal tissues. In addition, CTHRC1 coordinated the activity of ICP genes through diverse signal transduction pathways, was also associated with immune cell infiltration and the tumor microenvironment, and potentially represented a promising immunotherapy target. We identified CTHRC1-related genes across cancers using the GEPIA2 tool. The single-gene GO analysis of CTHRC1 across cancers showed that it was involved in some signaling pathways and biological processes, such as the Wnt signaling pathway, cell migration, and positive regulation of protein binding. The expression and function of CTHRC1 were also further verified in glioma tissues and cell lines. Conclusions CTHRC1 is overexpressed in various cancer types and functions as an important oncogene that may promote tumorigenesis and development through different mechanisms. CTHRC1 may represent an important therapeutic target for human cancers.

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“…At the same time, CD276 is also abnormally expressed in a variety of tumors and participates in tumor proliferation, apoptosis, differentiation, invasion and interepithelial transformation. Usually CD276 is up-regulated in tumors and is associated with poor prognosis of patients ( Liu S. et al, 2021 ). In NSCLC, a previous meta-analysis found that the high expression of CD276 was significantly associated with patients’ lymph node metastasis and advanced TNM staging ( Wu et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Pan-Cancer Biomarkers Based on the Gene Expression Profiles of Cancer Cell Lines

Ding

Zhang

et al. 2021

Front. Cell Dev. Biol.

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There are many types of cancers. Although they share some hallmarks, such as proliferation and metastasis, they are still very different from many perspectives. They grow on different organ or tissues. Does each cancer have a unique gene expression pattern that makes it different from other cancer types? After the Cancer Genome Atlas (TCGA) project, there are more and more pan-cancer studies. Researchers want to get robust gene expression signature from pan-cancer patients. But there is large variance in cancer patients due to heterogeneity. To get robust results, the sample size will be too large to recruit. In this study, we tried another approach to get robust pan-cancer biomarkers by using the cell line data to reduce the variance. We applied several advanced computational methods to analyze the Cancer Cell Line Encyclopedia (CCLE) gene expression profiles which included 988 cell lines from 20 cancer types. Two feature selection methods, including Boruta, and max-relevance and min-redundancy methods, were applied to the cell line gene expression data one by one, generating a feature list. Such list was fed into incremental feature selection method, incorporating one classification algorithm, to extract biomarkers, construct optimal classifiers and decision rules. The optimal classifiers provided good performance, which can be useful tools to identify cell lines from different cancer types, whereas the biomarkers (e.g. NCKAP1, TNFRSF12A, LAMB2, FKBP9, PFN2, TOM1L1) and rules identified in this work may provide a meaningful and precise reference for differentiating multiple types of cancer and contribute to the personalized treatment of tumors.

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The Role of CD276 in Cancers

Cited by 74 publications

References 86 publications

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Mitosis-related gene CENP-U as a potential biomarker in malignancy

Pan-cancer analysis combined with experiments predicts CTHRC1 as a therapeutic target for human cancers

Identification of Pan-Cancer Biomarkers Based on the Gene Expression Profiles of Cancer Cell Lines

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