B7-H3, Negatively Regulated by miR-128, Promotes Colorectal Cancer Cell Proliferation and Migration

Hu, Xiaomao; Xu, Minxian; Hu, Yangzhi; Li, Na; Zhou, Lei

doi:10.1007/s12013-021-00975-0

Cited by 19 publications

(12 citation statements)

References 28 publications

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“…Experimental studies in mice showed that induction of colitis and water avoidance stress affect levels of Mir29a and Mir29b and intestinal permeability in wildtype mice (71). Despite inconsistent results and conflicting conclusions of existing prognostic studies of B7-H3 (22,(24)(25)(26)(27)(28)(29)(30)(32)(33)(34)(35)(36)(37), our study, with the largest sample size, confirmed that it was a significant and independent biomarker to colon cancer survival by several trans-ethnical validations.…”

Section: Discussionsupporting

confidence: 63%

“…An array of studies have indicated that highly expressed B7-H3 promotes tumor progression and metastasis, as well as being associated with poor prognosis in various of cancers, including glioma (15), hepatocellular carcinoma (16), lung cancer (17), breast cancer (18), osteosarcoma (19), cutaneous melanoma (20), and pancreatic cancer (21). However, the results of existing prognostic studies of B7-H3 expression and colon cancer (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37) have been inconsistent and have presented conflicting conclusions; thus, we believe there is an urgent need to elaborate the effect of B7-H3 on colon cancer survival. Besides, various technical bottlenecks of previous studies need to be addressed: (I) there have been very few European studies (22,23,29), and majority of these studies were conducted among Asian populations (24)(25)(26)(27)(28)(30)(31)(32)(33)(34)(35)(36)(37); (II) no study so far has focused on the non-linear effects of B7-H3 on colon cancer survival, with previous studies simply having tested its linear effect; (III) there has been no independent validation of B7-H3, the association has consistently been evaluated in a single population; and (IV) there have been no trans-ethnic population studies of B7-H3 thus far.…”

Section: Introductionmentioning

confidence: 99%

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A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival

Gao¹,

Xu²,

Gao³

et al. 2021

J Gastrointest Oncol

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Background: There have been inconsistent results and conflicting conclusions among the existing prognostic studies of B7-H3 expression in colon cancer patients. Therefore, the association between B7-H3 expression and colon cancer survival has remained largely unclear.Methods: We performed a three-phase and trans-ethnic prognostic study of B7-H3 expression in colon cancer patients involving perhaps the largest population to date. In the discovery phase, we utilized a Cox proportional hazards model adjusted for covariates to test the association between B7-H3 expression and colon cancer overall survival (OS) time in a European population from The Cancer Genome Atlas (TCGA) cohort (n=433). In the validation phase I, the association was replicated in a European population from Gene Expression Omnibus (GEO) cohort (n=811). In the validation phase II, we again confirmed the significant association in an Asian population from Fujian Medical University Union Hospital (UNION) cohort (n=179).Furthermore, a series of Kaplan-Meier analysis, bioinformatics analysis of tumor immune microenvironment (TIME), and immune checkpoint prognostic prediction analysis, as well as sensitivity analysis, were also conducted.Results: Highly expressed B7-H3 was a significant and robust biomarker to colon cancer survival, with a large hazard ratio (HR) [HR TCGA =4.60, 95% confidence interval (CI): 2.15 to 9.83, P=8.37×10 −05 ; HR GEO =1.47, 95% CI: 1.12 to 1.94, P=0.0056; HR UNION =1.63, 95% CI: 1.36 to 1.95, P=7.91×10 −08 ]. We detected an involvement of B7-H3 in the tumor immune microenvironment (TIME). Meanwhile, B7-H3 was significantly and weakly correlated with 6 out of 27 well-recognized immune checkpoint genes. Even after adjusting for effects of other immune checkpoint genes, B7-H3 still exhibited a harmful effect on colon cancer survival using samples from TCGA and GEO cohorts (HR =1.47, 95% CI: 1.07 to 2.02, P=0.0184), indicating that it was an independent prognostic factor of colon cancer. We also proposed an immune checkpoint prognostic risk score which possessed the capability to identify colon cancers with high risk of mortality. Conclusions:The expression of B7-H3 is a significant, robust, and independent prognostic factor to colon cancer OS.

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Section: Discussionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival

Gao¹,

Xu²,

Gao³

et al. 2021

J Gastrointest Oncol

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“…Furthermore, miR-29 overexpression can inhibit B7-H3 expression levels, which play a crucial role in promoting medulloblastoma angiogenesis ( 21 ). Besides, B7-H3 expression is negatively regulated by miR-128 in colorectal cancer (CRC) ( 22 ).…”

Section: B7-h3 Is Highly Expressed In Different Types Of Human Cancersmentioning

confidence: 99%

B7-H3/CD276: An Emerging Cancer Immunotherapy

2021

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Immunotherapy aiming at suppressing tumor development by relying on modifying or strengthening the immune system prevails among cancer treatments and points out a new direction for cancer therapy. B7 homolog 3 protein (B7-H3, also known as CD276), a newly identified immunoregulatory protein member of the B7 family, is an attractive and promising target for cancer immunotherapy because it is overexpressed in tumor tissues while showing limited expression in normal tissues and participating in tumor microenvironment (TME) shaping and development. Thus far, numerous B7-H3-based immunotherapy strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Herein, we present the expression and biological function of B7-H3 in distinct cancer and normal cells, as well as B7-H3-mediated signal pathways in cancer cells and B7-H3-based tumor immunotherapy strategies. This review provides a comprehensive overview that encompasses B7-H3’s role in TME to its potential as a target in cancer immunotherapy.

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“…B7-H3 has been reported to promote cancer cell migration and invasion in various types of cancer [ 55 , 65 , 66 ]. In glioma cells overexpressing B7-H3, Zhong et al demonstrated that the JAK2/STAT3 signaling pathway was activated and that B7-H3-induced glioma progression was suppressed by a JAK2/STAT3 inhibitor.…”

Section: B7-h3 and Malignant Behaviorsmentioning

confidence: 99%

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Zhao

Xia

et al. 2022

J Hematol Oncol

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Immunotherapy for cancer is a rapidly developing treatment that modifies the immune system and enhances the antitumor immune response. B7-H3 (CD276), a member of the B7 family that plays an immunoregulatory role in the T cell response, has been highlighted as a novel potential target for cancer immunotherapy. B7-H3 has been shown to play an inhibitory role in T cell activation and proliferation, participate in tumor immune evasion and influence both the immune response and tumor behavior through different signaling pathways. B7-H3 expression has been found to be aberrantly upregulated in many different cancer types, and an association between B7-H3 expression and poor prognosis has been established. Immunotherapy targeting B7-H3 through different approaches has been developing rapidly, and many ongoing clinical trials are exploring the safety and efficacy profiles of these therapies in cancer. In this review, we summarize the emerging research on the function and underlying pathways of B7-H3, the expression and roles of B7-H3 in different cancer types, and the advances in B7-H3-targeted therapy. Considering different tumor microenvironment characteristics and results from preclinical models to clinical practice, the research indicates that B7-H3 is a promising target for future immunotherapy, which might eventually contribute to an improvement in cancer immunotherapy that will benefit patients.

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B7-H3, Negatively Regulated by miR-128, Promotes Colorectal Cancer Cell Proliferation and Migration

Cited by 19 publications

References 28 publications

A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival

A three-phase trans-ethnic study reveals B7-H3 expression is a significant and independent biomarker associated with colon cancer overall survival

B7-H3/CD276: An Emerging Cancer Immunotherapy

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

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