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MAGE-A genes as predictors of the outcome of laryngeal squamous cell carcinoma.

ABSTRACT: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors in the head and neck area. Melanoma-associated antigens A (MAGE-A) are strictly tumor-specific and are expressed in several types of tumors. To date, no studies have reported the potential of MAGE-A genes as markers for circulating tumor cells (CTCs) in patients with LSCC. The present study aimed to evaluate the expression and the possible prognostic significance of MAGE-A in the peripheral blood of patients with LSCC. In the present study, the expression of MAGE-A genes was determined by multiplex semi-nested PCR and restriction endonuclease treatment of the peripheral blood of patients with LSCC. The association between MAGE-A gene expression and clinicopathological parameters and prognosis was evaluated. The results demonstrated that the expression of MAGE-A was associated with the predictors that indicate poor prognosis. The expression levels of MAGE-A and each individual MAGE-A gene were also associated with a shorter overall survival time of patients with LSCC. In conclusion, the results of the present study suggested that the expression of MAGE-A genes may be a potential prognostic marker for patients with LSCC.

SUBMITTER: Liu S

PROVIDER: S-EPMC7418503 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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MAGE-A genes as predictors of the outcome of laryngeal squamous cell carcinoma.

Liu Shenghui S Zhao Yan Y Xu Yuru Y Sang Meixiang M Zhao Ruili R Gu Lina L Shan Baoen B

Oncology letters 20200729 4

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors in the head and neck area. Melanoma-associated antigens A (MAGE-A) are strictly tumor-specific and are expressed in several types of tumors. To date, no studies have reported the potential of <i>MAGE-A</i> genes as markers for circulating tumor cells (CTCs) in patients with LSCC. The present study aimed to evaluate the expression and the possible prognostic significance of <i>MAGE-A</i> in the peripheral blood of ...[more]

PMID: 32793312

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Project description:BackgroundLaryngeal squamous cell carcinoma (LSCC) is the prominent cancer in head and neck, which greatly affects life quality of patients. The pathogenesis of LSCC is not clear. Presently, the LSCC treatments include chemotherapy, surgery and radiotherapy; however, these methods have poor efficacy in patients with recurrent and persistent cancer. Therefore, the study identified the hub genes accompanied with LSCC, which may be a potential therapeutic target in the future.MethodsWe extracted whole transcriptome high-throughput sequencing (HTS) LSCC data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and calculate differentially expressed genes (DEGs) between LSCC and normal samples using statistical software RStudio. Through weighted gene co-expression network analysis (WGCNA), enrichment examination of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) functions, and examination of protein-protein interaction (PPI) network, we obtained network hub genes and validated the hub genes prognostic value and expression levels of protein.ResultsThrough analysis of differential gene expression, from the GEO and TCGA databases 2,139 and 2,774 DEGs were obtained, respectively, 13 and 15 modules were screened from TCGA-LSCC and GSE127165 datasets by WGCNA, respectively. The most significant positive and negative correlation modules in the WGCNA and DEG lists were overlapped, and overall 36 co-expressed overlapping genes were retrieved. Through enrichment analysis of GO and KEGG, it was found that the gene functions were highly concentrated in cell junction assembly, basement membrane, extracellular matrix (ECM) structural constituent etc., and the pathways were mainly concentrated in ECM receptor interaction, focal adhesion, small cell lung cancer, and toxoplasmosis. Through analysis of PPI network analysis, 10 network hub genes (SNAI2, ITGA6, LAMB3, LAMC2, CAV1, COL7A1, GJA1, EHF, OAT, and GPT) were obtained. Finally, survival analysis and protein expression validation of these genes confirmed that low OAT expression and high CAV1 expression remarkably influenced the survival of patient's prognosis with LSCC.ConclusionsWe recognized the hub genes and key modules nearly associated to LSCC and these genes were validated by survival analysis and the database of Human Protein Atlas (HPA), which is of high importance for unveiling the pathogenesis of LSCC and probing for new precise biological marker and potential therapeutic targets.

Project description:BackgroundLaryngeal squamous cell carcinoma (LSCC) is the second most aggressive head and neck squamous cell carcinoma. Although much work has been done to optimize its treatment, patients with LSCC still have poor prognosis. Therefore, figuring out differentially expressed genes (DEGs) contained in the progression of LSCC and employing them as potential therapeutic targets or biomarkers for LSCC is extremely meaningful.MethodsOverlapping DEGs were screened from two standalone Gene Expression Omnibus datasets, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed. By applying STRING and Cytoscape, a protein-protein network was built, and module analysis was carried out. The hub genes were selected by maximal clique centrality with the CytoHubba plugin of Cytoscape. UALCAN and GEPIA data were examined to validate the gene expression findings. Moreover, the connection of the hub genes with LSCC patient overall survival was studied employing The Cancer Genome Atlas. Then, western blot, qRT-PCR, CCK-8, wound healing and transwell assays were bring to use for further verify the key genes.ResultsA total of 235 DEGs were recorded, including 83 upregulated and 152 downregulated genes. A total of nine hub genes that displayed a high degree of connectivity were selected. UALCAN and GEPIA databases verified that these genes were highly expressed in LSCC tissues. High expression of the SPP1, SERPINE1 and Matrix metalloproteinases 1 (MMP1) genes was connected to worse prognosis in patients with LSCC, according to the GEPIA online tool. Western blot and qRT-PCR testify SPP1, SERPINE1 and MMP1 were upregulated in LSCC cells. Inhibition of SPP1, SERPINE1 and MMP1 suppressed cell proliferation, invasion and migration.ConclusionThe work here identified effective and reliable diagnostic and prognostic molecular biomarkers by unified bioinformatics analysis and experimental verification, indicating novel and necessary therapeutic targets for LSCC.

Project description:Laryngeal squamous cell carcinoma (LSCC) is the most common malignant tumor in the head and neck, and can seriously affect the daily life of patients. To study the mechanisms of LSCC, the microarray of GSE51958 was analyzed in the present study. GSE51958 was downloaded from Gene Expression Omnibus, and included a collection of LSCC tissue samples and matched adjacent non-cancerous tissue samples from 10 patients. Differentially-expressed genes (DEGs) were identified using limma package. Next, a weighted co-expression network was constructed for the DEGs by WGCNA package in R. Modules of the weighted co-expression network were obtained through constructing a hierarchical clustering tree using the hybrid dynamic shear tree method. Using the clusterProfiler package, the potential functions of DEGs in the modules correlated with LSCC were predicted by pathway enrichment analysis. In total, 959 DEGs were screened from the LSCC samples compared with the adjacent non-cancerous samples, including 553 upregulated and 406 downregulated genes. The appointed black, brown, gray, pink and yellow modules were screened for the DEGs in the weighted co-expression network. For the DEGs in the brown and yellow modules, the enriched pathways were cytokine-cytokine receptor interaction and metabolic pathways, respectively. The DEGs in the pink module were involved in the majority of pathways. With high connectivity degrees in the pink module, TPX2, microtubule-associated (TPX2; degree, 25), minichromosome maintenance complex component 2 (MCM2; degree, 25), ubiquitin-like with PHD and ring finger domains 1 (UHRF1; degree, 22), cyclin-dependent kinase 2 (CDK2; degree, 20) and protein regulator of cytokinesis 1 (PRC1; degree, 20) may be involved in LSCC. Overall, In conclusion, from the integrated bioinformatics analysis of genes that may be associated with LSCC, 959 DEGs were obtained from LSCC samples compared with adjacent non-cancerous samples, and TPX2, MCM2, UHRF1, CDK2 and PRC1 were found to hold a possible association with the disease.

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MAGE-A genes as predictors of the outcome of laryngeal squamous cell carcinoma.

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MAGE-A genes as predictors of the outcome of laryngeal squamous cell carcinoma.

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