Dataset Information

Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis.

ABSTRACT: Regional lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) is a crucial event for its progression, associated with a high rate of mortality. Sialidase, a key enzyme for the regulation of cellular sialic acids through catalyzing the initial step of degradation of glycoproteins and glycolipids, has been implicated in cancer progression. To facilitate the development of novel treatments for HNSCC, we have investigated whether sialidase is involved in the progression of this cancer. We found plasma membrane-associated sialidase (NEU3) to be significantly upregulated in tumor compared to non-tumor tissues; particularly, an increase in its mRNA levels was significantly associated with lymph node metastasis. To understand the mechanisms, we analyzed the NEU3-mediated effects on the malignant phenotype using squamous carcinoma HSC-2 and SAS cells. NEU3 promoted cell motility and invasion, accompanied by the increased expression of MMP-9, whereas NEU3 silencing or the activity-null mutant did not. NEU3 enhanced phosphorylation of epidermal growth factor receptor (EGFR), and an EGFR inhibitor, AG1478, abrogated the NEU3-induced MMP9 augmentation. These findings identify NEU3 as a participant in HNSCC progression through the regulation of EGFR signaling and thus as a potential target for inhibiting EGFR-mediated tumor progression.

SUBMITTER: Shiga K

PROVIDER: S-EPMC4714679 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis.

Shiga Kiyoto K Takahashi Kohta K Sato Ikuro I Kato Kengo K Saijo Shigeru S Moriya Setsuko S Hosono Masahiro M Miyagi Taeko T

Cancer science 20151016 11

Regional lymph node metastasis in head and neck squamous cell carcinoma (HNSCC) is a crucial event for its progression, associated with a high rate of mortality. Sialidase, a key enzyme for the regulation of cellular sialic acids through catalyzing the initial step of degradation of glycoproteins and glycolipids, has been implicated in cancer progression. To facilitate the development of novel treatments for HNSCC, we have investigated whether sialidase is involved in the progression of this can ...[more]

PMID: 26470851

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Project description:BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most serious diseases affecting populations worldwide and lymph node metastasis is a key pathological feature of HNSCC which predicts poor survival. However, the molecular mechanisms associated with the development of lymph node metastasis in HNSCC have not been fully elucidated.MethodsDifferentially expressed genes (DEGs) were identified in two HNSCC datasets (GES6631 and GES58911). Functional annotation analysis was constructed via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Meanwhile, the protein-protein interaction (PPI) network and module analysis using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and Cytoscape were carried out to identify the hub genes. The expression differences, overall survival (OS), and disease-free survival (DFS) of hub genes were analyzed by Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and verified by immunohistochemistry (IHC) from Human Protein Atlas (HPA). Moreover, receiver operating characteristic (ROC) curve analysis was conducted to judge whether those hub genes had good diagnostic and prognostic ability, and the web tool Tumor Immune Estimation Resource (TIMER) was used to analyze the correlation of hub genes' expression and immune infiltration.ResultsIn total, 913 DEGs including 476 upregulated and 437 downregulated genes were identified. The genes Aurora kinase A (AURKA), CyclinB1 (CCNB1), Cyclin-dependent kinase regulatory subunit 1B (CKS1B), Serpin Family H Member 1(SERPINH1), and Transforming growth factor-beta-induced protein (TGFBI) were screened out as hub genes and were associated with lymph node metastasis, showing notably abnormal expression in HNSCC samples, and the high expression of all the hub genes in HNSCC patients was related to worse overall survival.ConclusionsThe genes AURKA, CCNB1, CKS1B, SERPINH1, and TGFBI may be involved in the lymph node metastasis of HNSCC and reveal the potential to serve as molecular biomarkers in the diagnosis of HNSCC. This study may help to elucidate the molecular mechanisms of the development of lymph node metastasis and facilitate the selection of targets for the treatment and diagnosis of HNSCC.

Project description:ImportanceThere is a need to summarize the available evidence and provide quantitative data of the most important prognostic factors for patients with metastatic cutaneous squamous cell carcinoma of the head and neck region with regional lymph node metastasis (McSCCHN).ObjectiveTo undertake a PRISMA-compliant systematic review and meta-analysis of all published studies on the risk factors for overall survival (OS), locoregional control (LRC), locoregional recurrence (LRR), and disease-specific survival (DSS) for patients with McSCCHN.Data sourcesPubMed, CINAHL, and Embase were searched from 1946 to August 2018 for English-language articles.Study selectionInclusion criteria were randomized clinical trials or observational studies reporting on at least 10 patients with McSCCHN; studies analyzing 1 defined risk factor; reporting OS, LRC, LRR, or DSS; and clinical follow-up of 1 year of more. For the final analysis we included risk factors that were analyzed for the same outcome in at least 3 studies. Of the 2923 articles screened, 21 articles met the inclusion criteria.Data extraction and synthesisPRISMA guidelines were used for abstracting the data. Two reviewers independently abstracted the data. Risk of bias was estimated with the Newcastle-Ottawa Scale. Meta-analysis was performed using the random-effects model. All analysis took place between January and October 2018.Main outcomes and measuresThe primary end point was OS. Secondary end points included LRC, LRR, and DSS.ResultsA total of 20 observational studies and 1 randomized clinical trial were identified, representing 3534 patients (some reviewed articles reported no demographic characteristics), and were included in the analysis. Significant risk factors associated with OS were immunosuppression (hazard ratio [HR] of death, 2.66; 95% CI, 2.26-3.13), extracapsular spread (HR, 1.90; 95% CI, 1.12-3.23), adjuvant radiotherapy (HR, 0.45; 95% CI, 0.27-0.78), lymph node ratio (HR, 1.91; 95% CI, 1.09-3.35), and advanced age (HR, 1.03; 95% CI, 1.00-1.07). Immunosuppression (HR, 3.82; 95% CI, 2.47-5.92) and adjuvant radiotherapy (HR, 0.52; 95% CI, 0.33-0.84) were also significant risk factors for DSS.Conclusions and relevanceImmunosuppressed patients and those with extracapsular extension have poor prognosis. Adjuvant radiotherapy is associated with an improvement in OS. These risk factors will assist with better risk stratification and may also help to inform future clinical trials.

Dataset Information

Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis.

Publications

Upregulation of sialidase NEU3 in head and neck squamous cell carcinoma associated with lymph node metastasis.

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