FERMT1 promotes gastric cancer progression by activating the NF-κB pathway and predicts poor prognosis

Fan, Huiying; Zhang, Shengjun; Zhang, Yu; Wu, Liang; Cao, Bo

doi:10.1080/15384047.2020.1792218

Cited by 18 publications

(19 citation statements)

References 41 publications

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“…EPN3 expression is upregulated in wounded epithelial tissues and it can drive breast tumorigenesis by increasing E-cadherin endocytosis, EPN3 is overexpressed in 40% of breast cancers and its overexpression is an independent predictor of distant metastasis ( 13 , 14 ).. Envoplakin (EVPL) is a protein component of desmosomes and the DNA variant in intron of EVPL (rs2071194) has been found associated with papillary and follicular thyroid cancer risk ( 15 ). FERMT1, as an oncogene, promotes the degradation of IκBα, thereby activating NF-κB signaling and promoting gastric cancer ( 16 ). JAG2 is one of Notch ligands, which recently appear to exert various carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

A Four-Gene-Based Prognostic Model Predicts Overall Survival in Patients With Cutaneous Melanoma

Tong

Wang

2021

Front. Oncol.

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BackgroundCutaneous melanoma (CM) is one of the most aggressive cancers with highly metastatic ability. To make things worse, there are limited effective therapies to treat advanced CM. Our study aimed to investigate new biomarkers for CM prognosis and establish a novel risk score system in CM.MethodsGene expression data of CM from Gene Expression Omnibus (GEO) datasets were downloaded and analyzed to identify differentially expressed genes (DEGs). The overlapped DEGs were then verified for prognosis analysis by univariate and multivariate COX regression in The Cancer Genome Atlas (TCGA) datasets. Based on the gene signature of multiple survival associated DEGs, a risk score model was established, and its prognostic and predictive role was estimated through Kaplan-Meier (K-M) analysis and log-rank test. Furthermore, the correlations between prognosis related genes expression and immune infiltrates were analyzed via Tumor Immune Estimation Resource (TIMER) site.ResultsA total of 103 DEGs were obtained based on GEO cohorts, and four genes were verified in TCGA datasets. Subsequently, four genes (ADAMDEC1, GNLY, HSPA13, and TRIM29) model was developed by univariate and multivariate Cox regression analyses. The K-M plots showed that the high-risk group was associated with shortened survival than that in the low-risk group (P < 0.0001). Multivariate analysis suggested that the model was an independent prognostic factor (high-risk vs. low-risk, HR= 2.06, P < 0.001). Meanwhile, the high-risk group was prone to have larger breslow depth (P< 0.001) and ulceration (P< 0.001).ConclusionsThe four-gene risk score model functions well in predicting the prognosis and treatment response in CM and will be useful for guiding therapeutic strategies for CM patients. Additional clinical trials are needed to verify our findings.

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Section: Discussionmentioning

confidence: 99%

A Four-Gene-Based Prognostic Model Predicts Overall Survival in Patients With Cutaneous Melanoma

Tong

Wang

2021

Front. Oncol.

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“…Deleting FERMT3 function leads to leukocyte adhesion deficiency type III disease, characterized by a propensity to bleed and an impaired immune system [ 28 ]. Aberrant expression of kindlins has been investigated in several types of cancer [ 29 ]. As previously mentioned, aberrant FERMT1 expression has been reported in various human cancers.…”

Section: Discussionmentioning

confidence: 99%

FERMT1 contributes to the migration and invasion of nasopharyngeal carcinoma through epithelial–mesenchymal transition and cell cycle arrest

Zhang

Zhou

et al. 2022

Cancer Cell Int

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Background Fermitin family member 1 (FERMT1) is significantly overexpressed in human cancers and associated with poor prognosis, but its contributions to tumorigenesis and nasopharyngeal carcinoma (NPC) progression remain unclear. Methods The public GEO database was examined to investigate the role of FERMT1. Immunohistochemistry (IHC) staining of FERMT1 was performed in NPC tissues to corroborate the results. Western blotting and qRT-PCR were performed to test the expression of related proteins and mRNAs. Cell counting kit-8 assay (CCK8 assay) and colony formation assays were carried out to investigate the association of FERMT1 expression with NPC cell proliferation. The wound healing assay and Transwell assay were used to detect the migration and invasion of NPC cells. Flow cytometric analysis was conducted to detect the cell cycle transition of NPC cells. Co-immunoprecipitation (Co-IP) was employed to identify the correlation of FEMRT1 and Nod-like receptor family protein 3 (NLRP3). Xenograft tumors were generated to investigate the effect of FERMT1 on the growth of NPC cells in vivo. Results Here, we found that FERMT1 was upregulated in NPC tissues and correlated with the clinicopathological characteristics of NPC patients. Moreover, knockdown of FERMT1 significantly decreased cell proliferation, migration and invasion by mediating epithelial–mesenchymal transition (EMT) and cell cycle arrest of NPC cells both in vitro and in vivo. Knockdown FERMT1 inhibited EMT through directly binding to the NLRP3 and inhibited NF-kB signaling pathway. Conclusion These data indicated that FERMT1 could be a good potential therapeutic target for NPC treatment.

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“…Evidence has shown that kindlin-1 facilitates integrin-mediated TGF-β activation ( Rognoni et al, 2014 ). Upregulation of FERMT1 promotes the progression of gastric cancer ( Fan et al, 2020 ). Liu et al found that FERMT1 was overexpressed in colon adenocarcinoma, promoting epithelial-mesenchymal transition and metastasis ( Liu et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma

Xiao

Huang

et al. 2022

Front. Cell Dev. Biol.

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Background: Lung adenocarcinoma (LUAD) accounts for the majority of lung cancers, and the survival of patients with advanced LUAD is poor. The extracellular matrix (ECM) is a fundamental component of the tumor microenvironment (TME) that determines the oncogenesis and antitumor immunity of solid tumors. However, the prognostic value of extracellular matrix-related genes (ERGs) in LUAD remains unexplored. Therefore, this study is aimed to explore the prognostic value of ERGs in LUAD and establish a classification system to predict the survival of patients with LUAD.Methods: LUAD samples from The Cancer Genome Atlas (TCGA) and GSE37745 were used as discovery and validation cohorts, respectively. Prognostic ERGs were identified by univariate Cox analysis and used to construct a prognostic signature by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The extracellular matrix-related score (ECMRS) of each patient was calculated according to the prognostic signature and used to classify patients into high- and low-risk groups. The prognostic performance of the signature was evaluated using Kaplan–Meier curves, Cox regression analyses, and ROC curves. The relationship between ECMRS and tumor immunity was determined using stepwise analyses. A nomogram based on the signature was established for the convenience of use in the clinical practice. The prognostic genes were validated in multiple databases and clinical specimens by qRT-PCR.Results: A prognostic signature based on eight ERGs (FERMT1, CTSV, CPS1, ENTPD2, SERPINB5, ITGA8, ADAMTS8, and LYPD3) was constructed. Patients with higher ECMRS had poorer survival, lower immune scores, and higher tumor purity in both the discovery and validation cohorts. The predictive power of the signature was independent of the clinicopathological parameters, and the nomogram could also predict survival precisely.Conclusions: We constructed an ECM-related gene signature which can be used to predict survival and tumor immunity in patients with LUAD. This signature can serve as a novel prognostic indicator and therapeutic target in LUAD.

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FERMT1 promotes gastric cancer progression by activating the NF-κB pathway and predicts poor prognosis

Abstract: Cao (2020) FERMT1 promotes gastric cancer progression by activating the NF-κB pathway and predicts poor prognosis,

Cited by 18 publications

References 41 publications

A Four-Gene-Based Prognostic Model Predicts Overall Survival in Patients With Cutaneous Melanoma

A Four-Gene-Based Prognostic Model Predicts Overall Survival in Patients With Cutaneous Melanoma

FERMT1 contributes to the migration and invasion of nasopharyngeal carcinoma through epithelial–mesenchymal transition and cell cycle arrest

Integrative Analysis Constructs an Extracellular Matrix-Associated Gene Signature for the Prediction of Survival and Tumor Immunity in Lung Adenocarcinoma

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