Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Yang, Haoyu; Xu, Zixuan; Peng, Yuqian; Wang, Jiali; Xiang, Yang

doi:10.3390/biom11081197

Cited by 16 publications

(8 citation statements)

References 102 publications

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“…Research on glioblastoma and breast cancer supports the suggested pancancer involvement of integrin α6 in radioresistance [65] , [66] . Concerning integrin β4, a connection to EMT could be observed [67] , which was also identified as a hallmark ontology in our final aaGOI-All/RT set. Likewise, both of these integrins and their heterodimeric α6β4 receptors were found to be intricately involved in cancer stem cell (CSC) properties [46] and their deactivation demonstrated effective perturbation of CSC populations [68] , [69] .…”

Section: Discussionmentioning

confidence: 90%

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Borodins¹,

Broghammer²,

Seifert³

et al. 2023

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 90%

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Borodins¹,

Broghammer²,

Seifert³

et al. 2023

Computational and Structural Biotechnology Journal

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“…There is ample evidence that the most important functional states of cells (stemness, EMT, invasion, migration, proliferation, and tumor angiogenesis) are associated with α6β4 integrin expression ( Romagnoli et al, 2019 ; Bierie et al, 2017 ; Masugi et al, 2015 ; Yang et al, 2021 ; Roussellea & Scoazecb, 2020 ). It is also known that α6β4 expression is associated with a poor prognosis in breast cancer patients ( Lu et al, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

Integrin-associated transcriptional characteristics of circulating tumor cells in breast cancer patients

Grigoryeva,

Tashireva,

Alifanov

et al. 2024

PeerJ

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Background Integrins enable cell communication with the basal membrane and extracellular matrix, activating signaling pathways and facilitating intracellular changes. Integrins in circulating tumor cells (CTCs) play a significant role in apoptosis evasion and anchor-independent survival. However, the link between CTCs expressing different integrin subunits, their transcriptional profile and, therefore, their functional activity with respect to metastatic potential remains unclear. Methods Single-cell RNA sequencing of CD45-negative cell fraction of breast cancer patients was performed. All CTCs were divided into nine groups according to their integrin profile. Results СTCs without the gene expression of integrins or with the expression of non-complementary α and β subunits that cannot form heterodimers prevailed. Only about 15% of CTCs expressed integrin subunits which can form heterodimers. The transcriptional profile of CTCs appeared to be associated with the spectrum of expressed integrins. The lowest potential activity was observed in CTCs without integrin expression, while the highest frequency of expression of tumor progression-related genes, namely genes of stemness, epithelial-mesenchymal transition (EMT), invasion, proinflammatory chemokines and cytokines as well as laminin subunits, were observed in CTCs co-expressing ITGA6 and ITGB4. Validation on the protein level revealed that the median of integrin β4+ CTCs was higher in patients with more aggressive molecular subtypes as well as in metastatic breast cancer patients. One can expect that CTCs with ITGA6 and ITGB4 expression will have pronounced metastatic potencies manifesting in expression of EMT and stemness-related genes, as well as potential ability to produce chemokine/proinflammatory cytokines and laminins.

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“… 24 , 29 ITGB4 is a signaling protein that promotes intracellular signaling and protects the integrity of epithelial cells. 30 Moreover, bioinformatics analysis showed that ITGB4 acts as a pan-cancer oncogene in 33 different types of human tumors. 31 ITGB4 overexpression has been associated with venous invasion and decreased overall survival in patients with NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning

Wang¹,

Sun²,

Zhang³

2023

IJGM

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Background Lung adenocarcinoma (LUAD) is an aggressive cancer that has an extremely poor prognosis. As well as facilitating the detachment of cancer cells from the primary tumor site, anoikis plays an important role in cancer metastasis. Few studies to date, however, have examined the role of anoikis in LUAD, in patient prognosis. Methods A total of 316 anoikis-related genes (ANRGs) integrated from Genecards and Harmonizome portals. LUAD transcriptome data were retrieved from the Genotype-Tissue Expression Project (GEO) and The Cancer Genome Atlas (TCGA). Anoikis-related prognostic genes (ANRGs) were primarily screened by univariate Cox regression. All ANRGs were included in the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model to construct the powerful prognostic signature. This signature was validated and assessed using the Kaplan-Meier method as well as univariate and multivariate Cox regression analyses. Anoikis-related regulators of risk score were identified using a XG-boost machine learning model. The expression of ITGB4 protein was examined in a ZhengZhou University (ZZU) tissue cohort by immunohistochemistry, and the potential mechanisms of action of ITGB4 in LUAD were explored by GO, KEGG, and ingenuity pathway analyses and by GSEA. Results A risk score signature was constructed based on eight ANRGs, with high risk scores found to closely correlate with unfavorable clinical features. ITGB4 expression may be associated with 5-year over survival, with immunohistochemistry showed that the expression of ITGB4 was higher in LUAD than in nontumor tissues. Enrichment analysis suggested that ITGB4 may promote LUAD development by targeting E2F, MYC, and oxidative phosphorylation signaling pathways. Conclusion Our anoikis-related signature from RNA-seq data may be a novel prognostic biomarker in patients with LUAD. It may help physicians develop personalized LUAD treatments in clinical practice. Moreover, ITGB4 may affect the development of LUAD through the oxidative phosphorylation pathway.

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Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Cited by 16 publications

References 102 publications

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Meta-analysis of expression and the targeting of cell adhesion associated genes in nine cancer types – A one research lab re-evaluation

Integrin-associated transcriptional characteristics of circulating tumor cells in breast cancer patients

Identification and Validation of Anoikis-Related Signatures for Predicting Prognosis in Lung Adenocarcinoma with Machine Learning

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