<i>ITGB2 (</i>Integrin β2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis

George, Lovya; Menden, Heather; Sheng, Xia; Yu, Wei; Holmes, Anne; Johnston, Jeff; Reid, Kimberly J.; Josephson, Cassandra D.; Patel, Ravi; Ahmed, Atif; Mulrooney, Neil; Miller, Neil; Farrow, Emily; Sampath, Venkatesh

doi:10.1097/mpg.0000000000002941

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…They found that the upregulation of ITGB2 in NSCLC cell lines increased the expression of immune-related proteins, such as N-cadherin, snail, and slug, while decreasing the E-cadherin expression, laying the foundation for further research on immunotherapy. Regarding the non-tumor disorders, studies suggested that the upregulated mRNA expression level of ITGB2 in PBMCs (peripheral blood mononuclear cells) did not associate with disease severity of SSc patients, nor did the status in premature infants with NEC [ 36 , 37 ]. Our results highlight the potential ability of ITGB2 to be a regulator of immune infiltration and a marker of the response to immunotherapy for ovarian cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Identifying ITGB2 as a Potential Prognostic Biomarker in Ovarian Cancer

Deng

Cao

et al. 2023

Diagnostics

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Epithelial ovarian cancer is by far the most lethal gynecological malignancy. The exploration of promising immunomarkers to predict prognosis in ovarian cancer patients remains challenging. In our research, we carried out an integrated bioinformatic analysis of genome expressions and their immune characteristics in the ovarian cancer microenvironment with validation in different experiments. We filtrated 332 differentially expressed genes with 10 upregulated hub genes from the Gene Expression Omnibus database. These genes were closely related to ovarian tumorigenesis. Subsequently, the survival and immune infiltration analysis demonstrated that the upregulation of five candidate genes, ITGB2, VEGFA, CLDN4, OCLN, and SPP1, were correlated with an unfavorable clinical outcome and increased immune cell infiltration in ovarian cancer. Of these genes, ITGB2 tended to be the gene most correlated with various immune cell infiltrations and had a strong correlation with significant M2 macrophages infiltration (r = 0.707, p = 4.71 × 10−39), while it had a moderate correlation with CD4+/CD8+ T cells and B cells. This characteristic explains why the high expression of ITGB2 was accompanied by immune activation but did not reverse carcinogenesis. Additionally, we confirmed that ITGB2 was over-expressed in ovarian cancer tissues and was mainly located in cytoplasm, detected by Western blotting and the immunohistochemical method. In summary, ITGB2 may serve as a prognostic immunomarker for ovarian cancer patients.

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Section: Discussionmentioning

confidence: 99%

Identifying ITGB2 as a Potential Prognostic Biomarker in Ovarian Cancer

Deng

Cao

et al. 2023

Diagnostics

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“…The expression of ITGB2 was upregulated in atheroma plaque compared with intact tissue and involved in the development of carotid atherosclerosis [ 28 ]. Moreover, ITGB2 deficiency causes the hyperresponsiveness of the aberrant Toll-like receptor and leads to necrotizing enterocolitis pathogenesis [ 29 ]. In cancer studies, ITGB2 was found to be significantly elevated in high-malignant gliomas and related to a worse prognosis [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer

Zhou

et al. 2022

JCM

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Integrins are involved in extracellular and intracellular signaling and are often aberrantly expressed in tumors. Integrin beta 2 (ITGB2) has previously been demonstrated to be correlated with the host defense. However, the expression profile and role of ITGB2 in non-small-cell lung cancer (NSCLC) remain unclear. Here, we found that the genetic alterations in ITGB2 was predominated by gene mutation and copy number deletion using cBioPortal analysis, and its expression was downregulated in the NSCLC tissues, as validated by the UALCAN, TCGA, and GEO databases and our tissue samples. Kaplan–Meier (KM) plotter analysis revealed that patients with a lower ITGB2 expression had a shorter overall survival (OS) time (p = 0.01). Moreover, 1089 differentially expressed genes (DEGs) in the NSCLC tissues were screened using the TCGA database. The GO and KEGG enrichment analysis showed that the DEGs were closely associated with immune processes and cell adhesion. The protein–protein interaction (PPI) network revealed that 10 of 15 EMT-related genes among the DEGs might lead to the metastasis of NSCLC. Concomitantly, the expression of ITGB2 was positively correlated with the infiltration of Treg cells and Myeloid-derived suppressor cells (MDSC). Biologically, the ectopic expression of ITGB2 significantly inhibited the proliferation and metastasis of NSCLC cells. Mechanistically, we demonstrated that ITGB2 suppressed the expression of N-cadherin, Vimentin, Slug, Snail, and Twist, while it promoted E-cadherin expression, according to gain-of-function studies. In conclusion, ITGB2 can inhibit the proliferation and migration of NSCLC cells, leading to a poor prognosis, via epithelial–mesenchymal transition (EMT) signaling.

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“…ITGB2 is an inflammatory and immune‐related gene that participates in the inflammatory response and inflammatory tumour transformation during IBD carcinogenesis. 18 , 19 Another study reported that ITGB2 is closely associated with EMT in colorectal cancer (CRC). 20 IBD is closely associated with CRC, and patients with IBD are at higher risk of developing CRC.…”

Section: Introductionmentioning

confidence: 99%

ITGB2 related to immune cell infiltration as a potential therapeutic target of inflammatory bowel disease using bioinformatics and functional research

Xu,

Du,

Yang

et al. 2024

J Cellular Molecular Medi

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Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition regarded as a major risk factor for colitis‐associated cancer. However, the underlying mechanisms of IBD remain unclear. First, five GSE data sets available in GEO were used to perform ‘batch correction’ and Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). Candidate molecules were identified using CytoHubba, and their diagnostic effectiveness was predicted. The CIBERSORT algorithm evaluated the immune cell infiltration in the intestinal epithelial tissues of patients with IBD and controls. Immune cell infiltration in the IBD and control groups was determined using the least absolute shrinkage selection operator algorithm and Cox regression analysis. Finally, a total of 51 DEGs were screened, and nine hub genes were identified using CytoHubba and Cytoscape. GSE87466 and GSE193677 were used as extra data set to validate the expression of the nine hub genes. CD4‐naïve T cells, gamma–delta T cells, M1 macrophages and resting dendritic cells (DCs) are the main immune cell infiltrates in patients with IBD. Signal transducer and activator of transcription 1, CCR5 and integrin subunit beta 2 (ITGB2) were significantly upregulated in the IBD mouse model, and suppression of ITGB2 expression alleviated IBD inflammation in mice. Additionally, the expression of ITGB2 was upregulated in IBD‐associated colorectal cancer (CRC). The silence of ITGB2 suppressed cell proliferation and tumour growth in vitro and in vivo. ITGB2 resting DCs may provide a therapeutic strategy for IBD, and ITGB2 may be a potential diagnostic marker for IBD‐associated CRC.

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ITGB2 (Integrin β2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis

Cited by 7 publications

References 20 publications

Identifying ITGB2 as a Potential Prognostic Biomarker in Ovarian Cancer

Identifying ITGB2 as a Potential Prognostic Biomarker in Ovarian Cancer

The Profile and Clinical Significance of ITGB2 Expression in Non-Small-Cell Lung Cancer

ITGB2 related to immune cell infiltration as a potential therapeutic target of inflammatory bowel disease using bioinformatics and functional research

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