A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial–mesenchymal transition

Wang, Zhe; Fu, Liu; Zhang, Junjie; Ge, Yanli; Guo, Cheng; Wang, Rui; Deng, Min; Wang, Qizhi; Wang, Zhirong

doi:10.1186/s12938-022-00998-5

Cited by 3 publications

(2 citation statements)

References 43 publications

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“…According to a bioinformatics analysis-based study, it was shown that the overexpression of ITGBL1 had an impact on the overall survival. 21 Anoikis resistance exhibits a strong correlation with the processes of metastasis and tumour growth. 22,23 Thus, the identification of crucial regulators responsible for conferring resistance to anoikis, as well as understanding the underlying mechanisms via which their dysregulation occurs, holds significant importance in cancer progression.…”

Section: Discussionmentioning

confidence: 99%

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ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

Shen,

Xia,

Wang

et al. 2024

J Cellular Molecular Medi

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The resistance to anoikis plays a critical role in the metastatic progression of various types of malignancies, including gastric cancer (GC). Nevertheless, the precise mechanism behind anoikis resistance is not fully understood. Here, our primary focus was to examine the function and underlying molecular mechanism of Integrin beta‐like 1 (ITGBL1) in the modulation of anoikis resistance and metastasis in GC. The findings of our investigation have demonstrated that the overexpression of ITGBL1 significantly augmented the resistance of GC cells to anoikis and promoted their metastatic potential, while knockdown of ITGBL1 had a suppressive effect on both cellular processes in vitro and in vivo. Mechanistically, we proved that ITGBL1 has a role in enhancing the resistance of GC cells to anoikis and promoting metastasis through the AKT/Fibulin‐2 (FBLN2) axis. The inhibition of AKT/FBLN2 signalling was able to reverse the impact of ITGBL1 on the resistance of GC cells to anoikis and their metastatic capability. Moreover, the expression levels of ITGBL1 were found to be significantly elevated in the cancerous tissues of patients diagnosed with GC, and there was a strong correlation observed between high expression levels of ITGBL1 and worse prognosis among individuals diagnosed with GC. Significantly, it was revealed that within our cohort of GC patients, individuals exhibiting elevated ITGBL1 expression and diminished FBLN2 expression experienced the worst prognosis. In conclusion, the findings of our study indicate that ITGBL1 may serve as a possible modulator of resistance to anoikis and the metastatic process in GC.

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Section: Discussionmentioning

confidence: 99%

“…Nevertheless, there is a paucity of research examining the functions of ITGBL1 in GC. According to a bioinformatics analysis‐based study, it was shown that the overexpression of ITGBL1 had an impact on the overall survival 21 . A study by Yin et al.…”

Section: Discussionmentioning

confidence: 99%

ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

Shen,

Xia,

Wang

et al. 2024

J Cellular Molecular Medi

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A multi-cancer analysis unveils ITGBL1 as a cancer prognostic molecule and a novel immunotherapy target

Wu,

Liu,

et al. 2024

Oncologie

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Objectives Integrin subunit beta-like 1 (ITGBL1), a member of the epidermal growth factor (EGF)-like protein family, encodes a beta integrin-related protein that is mainly associated with the development of specific tumours and immune-related signalling pathways. This work aimed to explore the possibility that ITGBL1 functions as a novel target gene for immunotherapy and could be a cancer prognostic molecule. Methods The mRNA data for ITGBL1 were obtained from the public databases The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO). Using GEPIA, the differential expression of ITGBL1 in different tumour stages was identified. Cancer prognostic correlations were explored using Kaplan–Meier survival analysis and forest plots. A combination of Gene Set Enrichment Analysis (GSEA), TIMER2.0 and the R package was applied to analyse the ITGBL1-enriched related pathways. The NCI-60 drug database was examined using CellMinerTM. Cytological experiments were conducted to confirm ITGBL1’s impact on cancer cells. Results Our research has shown that ITGBL1 is differentially expressed in 26 cancers, and high ITGBL1 expression predicts a poorer survival prognosis in some specific cancers. Additionally, we found that ITGBL1 is enriched in immune-related pathways, which are closely linked to immunomodulatory molecules, immune-infiltrating cells, and immunomodulatory factors. The results of tumor mutational burden (TMB) and microsatellite instability (MSI) also indicate that the expression of ITGBL1 is beneficial for improving tumor immunotherapy efficacy. Furthermore, a number of antitumor agents associated with ITGBL1 expression have been identified. Finally, knockdown of ITGBL1 restricts the ability of gastric and colorectal cancer cells to proliferate and migrate. Conclusions Our study demonstrates that ITGBL1 can be utilized to accurately prognosticate cancer and has opened up new avenues for the investigation of tumor immune mechanisms and the development of more efficacious immunotherapies.

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The function of guanylate binding protein 3 (GBP3) in human cancers by pan-cancer bioinformatics

Jiang

Jin

Guo-xiu

et al. 2023

MBE

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<abstract> <p>As a guanylate binding protein (GBPs) member, GBP3 is immune-associated and may participate in oncogenesis and cancer therapy. Since little has been reported on GBP3 in this field, we provide pan-cancer bioinformatics to investigate the role of GBP3 in human cancers. The GBP3 expression, related clinical outcomes, immune infiltrates, potential mechanisms and mutations were conducted using tools including TIMER2.0, GEPIA2.0, SRING, DAVID and cBioPortal. Results showed an increased risk of high GBP3 in Brain Lower Grade Glioma (LGG) and Lung Squamous Cell Carcinoma (LUSC) and a decreased risk of GBP3 in Sarcoma (SARC) and Skin Cutaneous Melanoma (SKCM) (p ≤ 0.05). GBP3 was negatively correlated with CAFs in Esophageal Adenocarcinoma (ESCA) and positively correlated with CAFs in LGG, LUSC and TGCG (p ≤ 0.05). In addition, GBP3 was positively correlated with CD8+ T cells in Bladder Urothelial Carcinoma (BLCA), Cervical Squamous Cell Carcinoma (CESC), Kidney Renal Clear Cell Carcinoma (KIRC), SARC, SKCM, SKCM-Metastasis and Uveal Melanoma (UVM) (p ≤ 0.05). Potentially, GBP3 may participate in the homeostasis between immune and adaptive immunity in cancers. Moreover, the most frequent mutation sites of GBP3 in cancers are R151Q/<sup>*</sup> and K380N. This study would provide new insight into cancer prognosis and therapy.</p> </abstract>

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A comprehensive analysis of potential gastric cancer prognostic biomarker ITGBL1 associated with immune infiltration and epithelial–mesenchymal transition

Cited by 3 publications

References 43 publications

ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

ITGBL1 promotes anoikis resistance and metastasis in human gastric cancer via the AKT/FBLN2 axis

A multi-cancer analysis unveils ITGBL1 as a cancer prognostic molecule and a novel immunotherapy target

The function of guanylate binding protein 3 (GBP3) in human cancers by pan-cancer bioinformatics

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