scholarly journals Increased Expression of FN1 in Head and Neck Squamous Cell Carcinoma Predicts Poor Prognosis

2021 ◽  
Author(s):  
Hung-Sheng Shih ◽  
Li-Yu Hung ◽  
Ming-Yu Hsieh
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Kaplan Meier

Abstract Background: A few recent studies have addressed the function of FN1 (Fibronectin 1) in head and neck cancer. The clinical information from 500 HNSCC (Head and neck squamous cell carcinoma) patients with FN1 gene expression data set was published by The Cancer Genome Atlas (TCGA). The correlation between clinicopathologic characteristics and FN1 expression was analyzed by Logistic regression and Wilcoxon signed rank test. Survival function was performed employing Kaplan-Meier estimator, and the relationship between clinicopathological characteristics, prognostic outcome, and FN1 expression were examined by using Cox regression analysis. As Gene set enrichment analysis (GSEA) was performed, we investigated the correlation between FN1 expression and immune cell infiltrates with single-sample gene set enrichment analysis (ssGSEA). Results: Patients with high FN1 expression revealed a significantly decreased overall survival (OS), and disease-specific survival (DSS) than those with low FN1 expression in Kaplan-Meier survival analyses. According to the above results, univariate and multivariate analysis revealed that patients with high FN1 expression had lower OS than those with low FN1 expression.Conclusions: The findings of this research provide insights for FN1 may be potential prognostic biomarkers for diagnosis as well as therapeutic targets in HNSCC patients.

scholarly journals Upregulated Glycolysis Correlates With Clinical and Transcriptomic Significances in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Hideyuki Takahashi ◽  
Reika Kawabata-Iwakawa ◽  
Shota Ida ◽  
Ikko Mito ◽  
Hiroe Tada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Janus Kinase ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Tumor Type ◽  
High Group

Abstract Altered metabolism is an emerging hallmark of cancer. Cancer cells preferentially utilize glycolysis for energy production, termed “aerobic glycolysis.” In this study, we performed a comprehensive analysis of the glycolysis status in the tumor microenvironment (TME) of head and neck squamous cell carcinoma (HNSCC) using data from The Cancer Genome Atlas database. We first divided 520 patients with HNSCC into two groups based on the mRNA expression of 16 glycolysis-related genes. The glycolysis-high signature positively correlated with human papillomavirus-negative tumor type, advanced T factor, and unfavorable prognosis. The gene set enrichment analysis revealed upregulation of several pathways, including interferon-alpha response, myc targets, hypoxia, epithelial-mesenchymal transition, transforming growth factor-β signaling, and interleukin 6-Janus kinase-signal transducer and activator of transcription 3 signaling, in the glycolysis-high group. Immune cell enrichment analysis revealed decreased infiltration of T cells, dendritic cells, and B cells in the glycolysis-high group, suggesting impaired tumor antigen presentation, T cell activation, and antibody production in TME. Moreover, the expression of TGFB1, CD274, and PDCD1LG2, which facilitate immunosuppression in the TME, was upregulated in the glycolysis-high group. Collectively, these findings suggest the potential of glycolysis monitoring as a biomarker for tumor progression and immunosuppression in the TME of HNSCC.

scholarly journals Upregulated glycolysis correlates with tumor progression and immune evasion in head and neck squamous cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideyuki Takahashi ◽  
Reika Kawabata-Iwakawa ◽  
Shota Ida ◽  
Ikko Mito ◽  
Hiroe Tada ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Evasion ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Glycolytic Activity

AbstractAltered metabolism is an emerging hallmark of cancer. Cancer cells preferentially utilize glycolysis for energy production, termed “aerobic glycolysis.” In this study, we performed a comprehensive analysis of the glycolytic activity in head and neck squamous cell carcinoma (HNSCC) using data obtained from The Cancer Genome Atlas database. We first divided 520 patients with HNSCC into four groups based on the mRNA expression of 16 glycolysis-related genes. The upregulated glycolytic activity positively correlated with human papillomavirus-negative tumor type, advanced T factor, and unfavorable prognosis. The gene set enrichment analysis revealed upregulation of several hallmark pathways, including interferon-alpha response, myc targets, unfolded protein response, transforming growth factor-β signaling, cholesterol homeostasis, and interleukin 6-Janus kinase-signal transducer and activator of transcription 3 signaling, in the glycolysis-upregulated groups. Immune cell enrichment analysis revealed decreased infiltration of T cells, dendritic cells, and B cells in the glycolysis-upregulated groups, suggesting impaired tumor antigen presentation, T cell activation, and antibody production in the TME. Moreover, the expression profile of immune-related genes indicated increased immune evasion in the glycolysis-upregulated tumors. Collectively, these findings suggest that transcriptome analysis of glycolytic activity of tumors has the potential as a biomarker for tumor progression and immunological status in patients with HNSCC.

scholarly journals Investigating resistin like beta (RETNLB) as a tumor promoter for oral squamous cell carcinoma

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Hong Jin ◽  
Hui Miao ◽  
Yuan-Wen Nie ◽  
Yang-Yang Lin
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Toll Like Receptor ◽  
Gene Set Enrichment ◽  
Gene Set

Abstract Background Oral cavity cancer ranks the sixth most common malignancy worldwide, of which oral squamous cell carcinoma is the predominant type. This study aimed to investigate the function and the underlying mechanism of resistin like beta (RETNLB) in oral squamous cell carcinoma. Methods The data of oral squamous cell carcinoma samples from The Cancer Genome Atlas database was used to examine RETNLB expression and assess its correlation with the clinical outcomes. Biological functions of RETNLB on the growth, invasion and migration of cells were determined by cell counting kit 8, clonogenic growth, and Transwell assays. Gene set enrichment analysis was utilized to identify the important gene sets associated with RETNLB expression, which was further confirmed by western blot. Results We found that RETNLB was upregulated in oral squamous cell carcinoma tissues and cells. High expression of RETNLB was closely linked to age and pathological tumor, and significantly related to poor survival of oral squamous cell carcinoma patients. Further functional experiments showed that knockdown of RETNLB significantly reduced the viability, mobility and invasiveness of cells. Moreover, gene set enrichment analysis suggested that Toll-like receptor signaling pathway was significantly correlated with high RETNLB expression. Further western blot analysis verified that silencing RETNLB could notably suppress the protein levels of Toll-like receptor 2, Toll-like receptor 4 and phosphor- extracellular signal-regulated kinase. Conclusions These results suggested that downregulation of RETNLB may restrain the progression of oral squamous cell carcinoma by inactivating TLR/2/4/ERK pathway.

scholarly journals YRNAs: New Insights and Potential Novel Approach in Head and Neck Squamous Cell Carcinoma

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1281 ◽  
Author(s):  
Kacper Guglas ◽  
Tomasz Kolenda ◽  
Maciej Stasiak ◽  
Magda Kopczyńska ◽  
Anna Teresiak ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Cell Lines ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
High Expression ◽  
Ribonucleoprotein Particle ◽  
Hnscc Cell

YRNAs are a class of non-coding RNAs that are components of the Ro60 ribonucleoprotein particle and are essential for initiation of DNA replication. Ro60 ribonucleoprotein particle is a target of autoimmune antibodies in patients suffering from systemic lupus erythematosus and Sjögren’s syndrome. Deregulation of YRNAs has been confirmed in many cancer types, but not in head and neck squamous cell carcinoma (HNSCC). The main aim of this study was to determine the biological role of YRNAs in HNSCC, the expression of YRNAs, and their usefulness as potential HNSCC biomarkers. Using quantitative reverse transcriptase (qRT)-PCR, the expression of YRNAs was measured in HNSCC cell lines, 20 matched cancer tissues, and 70 FFPETs (Formaline-Fixed Paraffin-Embedded Tissue) from HNSCC patients. Using TCGA (The Cancer Genome Atlas) data, an analysis of the expression levels of selected genes, and clinical-pathological parameters was performed. The expression of low and high YRNA1 expressed groups were analysed using gene set enrichment analysis (GSEA). YRNA1 and YRNA5 are significantly downregulated in HNSCC cell lines. YRNA1 was found to be significantly downregulated in patients’ tumour sample. YRNAs were significantly upregulated in T4 stage. YRNA1 showed the highest sensitivity, allowing to distinguish healthy from cancer tissue. An analysis of TCGA data revealed that expression of YRNA1 was significantly altered in the human papilloma virus (HPV) infection status. Patients with medium or high expression of YRNA1 showed better survival outcomes. It was noted that genes correlated with YRNA1 were associated with various processes occurring during cancerogenesis. The GSEA analysis showed high expression enrichment in eight vital processes for cancer development. YRNA1 influence patients’ survival and could be used as an HNSCC biomarker. YRNA1 seems to be a good potential biomarker for HNSCC, however, more studies must be performed and these observations should be verified using an in vitro model.

scholarly journals A panel of Transcription factors identified by data mining can predict the prognosis of head and neck squamous cell carcinoma

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Boxin Zhang ◽  
Haihui Wang ◽  
Ziyan Guo ◽  
Xinhai Zhang
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Risk Score ◽  
Squamous Cell ◽  
Gene Set Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Clinicopathological Parameters

Abstract Background Transcription factors (TFs) are responsible for the regulation of various activities related to cancer like cell proliferation, invasion, and migration. It is thought that, the measurement of TFs levels could assist in developing strategies for diagnosis and prognosis of cancer detection. However, due to lack of effective genome-wide tests, this cannot be carried out in clinical settings. Methods A complete assessment of RNA-seq data in samples of a head and neck squamous cell carcinoma (HNSCC) cohort in The Cancer Genome Atlas (TCGA) database was carried out. From the expression data of six TFs, a risk score model was developed and further validated in the GSE41613 and GSE65858 series. Potential functional roles were identified for the six TFs via gene set enrichment analysis. Results Based on our multi-TF signature, patients are stratified into high- and low-risk groups with significant variations in overall survival (OS) (median survival 2.416 vs. 5.934 years, log-rank test P < 0.001). The sensitivity and specificity evaluation of our multi-TF for 3-year OS in TCGA, GSE41613 and GSE65858 was 0.707, 0.679 and 0.605, respectively, demonstrating good reproducibility and robustness for predicting overall survival of HNSCC patients. Through multivariate Cox regression analyses (MCRA) and stratified analyses, we confirmed that the predictive capability of this risk score (RS) was not dependent on any of other factors like clinicopathological parameters. Conclusions With the help of a RS obtained from a panel of TFs expression signatures, effective OS prediction and stratification of HNSCC patients can be carried out.

scholarly journals Single Nucleotide Polymorphisms in Four Genes Associated with Survival Outcome for Patients with Head and Neck Squamous Cell Carcinoma

2020 ◽  
pp. 1-10
Author(s):  
Ren Sheng Wang ◽  
Chang Liu ◽  
Jing Lin Mi ◽  
Meng Xu ◽  
Ren Sheng Wang
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Nucleotide Polymorphisms ◽  
Bioinformatics Pipeline ◽  
Related Data ◽  
Kaplan Meier

Background: This study aimed to use a bioinformatics pipeline to explore the underlying mechanisms and identify genetic mutations that can be utilized to prognosticate individuals with head and neck squamous cell carcinoma (HNSCC). Methods: SNP-related data was accessed using the TCGA database. Mutation and expression analyses were performed between the mutant samples and wild-type samples. Kaplan‐Meier analysis was conducted to select the candidate mutant genes that affect overall survival. Correlation analysis, GSEA analysis and drug sensitivity analysis of the candidate genes were performed. Results: Down-regulation of FAT1, KMT2B, XIRP2 and ZNF347 expression were observed in the tumors with mutations. Kaplan‐Meier analysis indicated that reduced levels of FAT1, XIRP2 was significantly associated with better overall survival, while reduced levels of KMT2B, and ZNF347 were significantly correlated to worse overall survival. Additionally, SNPs of the four genes were found to participate in several pathways associated with HNSCC development. Furthermore, FAT1 mutation was sensitive to several anti-tumor drugs, such as PI-103, Belinostat and Ruxolitinib. Conclusion: SNPs in FAT1, KMT2B, XIRP2 and ZNF347 may be used as prognostic biomarkers in the treatment of HNSCC.

scholarly journals LIM Homeobox Transcription Factors as Novel Prognosis Biomarkers in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Chen Lu ◽  
Cong-cong Duan ◽  
Han Bing
Keyword(s):  
Squamous Cell Carcinoma ◽  
Transcription Factors ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Neck Squamous Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Clinical Variables

Abstract Background: LIM class homeobox (LHX) genes, an important subfamily of the homeobox genes, encode transcription factors that have a fundamental role during embryonic development. However, knowledge regarding the function and mechanism of LHXs in head and neck squamous cell carcinoma (HNSCC) is still lacking. Methods: We conduct a bioinformatic analysis to systematically explore the mRNA expression, clinical correlation, prognostic values, and underlying mechanisms of distinct LHXs in HNSCC. The differentially expressed mRNAs in the LIM homeobox gene family and their correlation with clinical variables were determined and verified with packages in software R. The prognosis values of LHXs expression levels were evaluated by Kaplan-Meier (KM) method and Cox proportional hazard model. Gene set enrichment analysis (GSEA) was conducted to understand the potential biological function of LHXs. The immune cell infiltration patterns were estimated through CIBERSORT and TIMER, and the methylation levels of LHXs in HNSCC were explored in UALCAN and MEXPRESS.Results: We found that among 12 LHXs, 8 genes (ISL1, LHX1-3, 5, 9, LMX1A, and LMX1B) showed altered expression in HNSCC tissues and detected significant correlations between their expression and clinical variables. Survival analysis revealed that LHX1, LHX5, LMX1A, LMX1B can serve as unfavorable prognosis predictors, and ISL1, LHX2, LHX9 can serve as favorable predictors in all HNSCC patients. Gene sets enrichment analysis and immune infiltration analyses showed that the aberrant expression of LHXs was closely related to cancer-associated processes and immune cell infiltration patterns. Finally, we observed hyper-methylation in the promoters of ISL1, LHX2, 5, 9, LMX1A, LMX1B and hypo-methylation in LHX3 promoter, suggesting the regulatory mechanism of LHXs abnormal expression may be related to aberrant DNA methylation. Conclusions: Our study found the oncogenic roles of LHX1,5 and LMX1B and the tumor-suppressor roles of ISL1 and LHX2 in patients with HNSCC, suggesting these LHXs as novel diagnostic and prognostic biomarkers for HNSCC.

scholarly journals A magasabb vérlemezkeszám mint a fej-nyak tumoros betegek túléléssel kapcsolatos esetleges prognosztikai faktora

2021 ◽  
Vol 162 (17) ◽  
pp. 676-682
Author(s):  
Zsuzsanna Szilasi ◽  
Valéria Jósa ◽  
Zsombor Zrubka ◽  
Tünde Mezei ◽  
Keresztély Merkel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Platelet Count ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Neck Squamous Cell Carcinoma ◽  
Anatomical Location ◽  
Kaplan Meier ◽  
The Impact

Összefoglaló. Bevezetés: Régóta ismert, hogy a daganatokhoz társuló emelkedett vérlemezkeszám rosszabb túléléssel társul. Fej-nyak tumoros betegek esetében kevés információ áll rendelkezésünkre ezzel az összefüggéssel kapcsolatban. Célkitűzés: Vizsgálatunk célja a fej-nyak daganatos betegek prognózisa és a thrombocytosis közötti összefüggés tanulmányozása volt. Módszer: Különféle stádiumú és lokalizációjú, 312, fej-nyak tumoros beteg retrospektív adatait elemeztük. A műtét előtti vérlemezkeszámokat vizsgáltuk, a 300 G/l feletti értéket tekintettük emelkedett thrombocytaszámnak. A vérlemezkeszám és a túlélés közötti kapcsolatot Kaplan–Meier-módszerrel és multivariáns Cox-regresszióval elemeztük. Eredmények: Emelkedett thrombocytaszám mellett szignifikánsan rosszabb túlélést észleltünk (5 éves túlélés: p = 0,007, betegségmentes túlélés: p = 0,192). Ez az összefüggés még akkor is fennállt, amikor multivariáns analízissel nemre, korra, stádiumra, differenciáltsági fokra, lokalizációra, valamint fehér- és vörösvérsejtszámra korrigáltuk az elemzést (5 éves túlélés: p = 0,027). A különféle anatómiai lokalizációkban eltérő mértékben észleltünk 300 G/l feletti vérlemezkeszámot (algarat: 43,6%, sub- és supraglottis: 35,8%, szájüreg: 35,7%, hangszalag: 22,5%, szájgarat: 19%, multiplex: 50%), ez azonban nem befolyásolta szignifikánsan a túlélést (p = 0,603). Következtetés: A daganathoz társuló thrombocytosis összefüggésbe hozható a fej-nyak tumoros betegek rosszabb túlélésével. Az egyes lokalizációkban talált különböző vérlemezkeszámok nem befolyásolják eltérő mértékben a túlélést. Orv Hetil. 2021; 162(17): 676–682. Summary. Introduction: The association between cancer-related thrombocytosis and worse survival has been described with a variety of solid neoplasms. However, only limited data are available on the prognostic significance of elevated platelet count in head and neck tumours. Objective: We aimed to investigate the correlation between the survival of patients with head and neck cancer and thrombocytosis. Method: We conducted an analysis of the data from 312 patients with head and neck squamous cell carcinoma of various stages and locations. Preoperative platelet counts were analysed; elevated platelet count was defined as 300 G/l or higher. The influence of platelet count on survival was calculated with the Kaplan–Meier method as well as with multivariate Cox regression. Results: In patients with excessive thrombocytosis, survival was significantly worse (overall survival: p = 0.007, disease-free survival: p = 0.192). This association remained significant even after adjusting the multivariate analysis for age, gender as well as tumour stage, grade, location, red and white blood cell count (overall survival: p = 0.027). The magnitude of thrombocytosis differed among tumours of different anatomical locations (hypopharynx: 43.6%, sub- and supraglottis: 35.8%, oral cavity: 35.7%, vocal cord: 22.5%, oropharynx: 19%, multiple: 50%), but this did not affect survival significantly (p = 0.603). Conclusion: Elevated platelet count may be related to a worse prognosis in head and neck squamous cell carcinoma patients. The impact of thrombocytosis does not vary with the anatomical location of the tumour. Orv Hetil. 2021; 162(17): 676–682.

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