scholarly journals FOXL2 expression might be a novel prognostic biomarker in patients with laryngeal squamous cell carcinoma

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052091925
Author(s):  
Jun Ge ◽  
Li Jiang ◽  
Yuke Tian ◽  
Min Zheng ◽  
Meiling Huang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Dna Amplification ◽  
Progression Free Survival ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Gene Body

Objectives This study aimed to explore the expression profile of the Forkhead box protein L2 gene ( FOXL2) and to determine its prognostic value and associated epigenetic and genetic alterations in patients with laryngeal squamous cell carcinoma (LSCC). Materials and methods Data for a subset of patients with LSCC (N = 116) were extracted from the head and neck squamous cell carcinoma dataset of The Cancer Genome Atlas and analyzed in relation to FOXL2 expression and survival. Results Aberrant FOXL2 expression was an independent prognostic factor for progression-free survival (PFS) (hazard ratio (HR): 2.63, 95% confidence interval (CI): 1.34–5.18) and overall survival (OS) (HR: 2.39, 95%CI: 1.28–4.46). Two gene-body CpG sites (cg10554436 and cg23637494) were moderately and positively correlated with FOXL2 expression. DNA amplification (+2/+1) was common (82/115, 71%) in LSCC, and FOXL2 expression was significantly upregulated in the high-amplification group (+2) compared with copy-neutral (0) cases. Conclusion Aberrant FOXL2 expression may be a novel prognostic biomarker for PFS and OS among patients with LSCC. FOXL2 upregulation may be related to gene-body hypermethylation and DNA amplification.

scholarly journals SHISA3Promoter Methylation Is a Potential Diagnostic and Prognostic Biomarker for Laryngeal Squamous Cell Carcinoma

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhisen Shen ◽  
Chongchang Zhou ◽  
Jinyun Li ◽  
Dong Ye ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Promoter Methylation ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Promoter Hypermethylation ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Qrt Pcr

The purpose of this study was to evaluate the contribution ofSHISA3promoter methylation to laryngeal squamous cell carcinoma (LSCC).SHISA3promoter methylation status and expression were determined using methylation-specific polymerase chain reaction (MSP) and quantitative real-time PCR (qRT-PCR) in 93 paired LSCC and adjacent normal tissues, respectively. Furthermore, the regulatory function of theSHISA3promoter fragment was analyzed using a luciferase reporter assay. The results reveal that there is a significant increase inSHISA3methylation in LSCC tissues compared with corresponding nontumor tissuesP=4.58E-12. The qRT-PCR results show a significant association betweenSHISA3methylation and expression in LSCCP=1.67E-03. In addition, the area under the receiver operating characteristic curve was 0.91. Consequently, a log-rank test and multivariate Cox analysis suggest thatSHISA3promoter hypermethylation is a predictor of poor overall survival for LSCC (log-rankP= 0.024; HR = 2.71; 95% CI = 1.024–7.177;P= 0.047). The results indicate thatSHISA3promoter hypermethylation might increase the risk of LSCC through regulation of gene expression and is a potential diagnostic and prognostic biomarker for LSCC.

scholarly journals Prognostic Analysis of Preoperative Inflammatory Biomarkers in Patients With Laryngeal Squamous Cell Carcinoma

2019 ◽  
Vol 99 (6) ◽  
pp. 371-378 ◽  
Author(s):  
Youfang Xun ◽  
Maohua Wang ◽  
Haiyong Sun ◽  
Shujun Shi ◽  
Bing Guan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Progression Free Survival ◽  
Inflammatory Biomarkers ◽  
Distribution Width ◽  
Free Survival ◽  
Lymphocyte Ratio

Objective: The purpose of this study was to demonstrate the prognostic role of inflammatory biomarkers in patients with laryngeal squamous cell carcinoma. Methods: For this study, we enrolled 151 patients who had undergone surgery for laryngeal squamous cell carcinoma. We assessed the preoperative neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), mean platelet volume, red cell distribution width, and alkaline phosphatase. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards model were conducted on overall survival, progression-free survival, locoregional recurrence-free survival, and distant metastasis-free survival of patients with laryngeal squamous cell carcinoma. Results: Both Kaplan-Meier analysis and univariate analysis showed significant prognostic differences with age, laryngectomy methods, Tumor Node Metastasis (TNM) staging, tumor location, NLR, PLR, MLR, and mean platelet volume. Multivariate analysis indicated that NLR (overall survival: hazard ratio [HR] = 3.02, 95% confidence interval [CI]: 1.28-7.10, P = .011), PLR (overall survival: HR = 0.33, 95% CI: 0.14-0.78, P = .011; progression-free survival: HR = 0.016,95% CI: 0.10-0.79, P = .016), and MLR (overall survival: HR = 0.29, 95% CI: 0.11-0.76, P = .012) were independent prognostic factors for 5-year survival. However, red cell distribution width and alkaline phosphatase had no significant difference in overall survival and progression-free survival. Conclusions: Preoperative high NLR, PLR, and MLR were associated with poor prognosis. They were found to be effective and reliable inflammatory biomarkers for patients with laryngeal squamous cell carcinoma.

scholarly journals Deletion of p53 and Hyper-Activation of PIK3CA in Keratin-15+ Stem Cells Lead to the Development of Spontaneous Squamous Cell Carcinoma

2020 ◽  
Vol 21 (18) ◽  
pp. 6585
Author(s):  
Samantha M. Y. Chen ◽  
Bian Li ◽  
Andrew G. Nicklawsky ◽  
Alexandra L. Krinsky ◽  
Tonya Brunetti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Model ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Loss Of Function

Squamous cell carcinoma (SCC) is the second commonest type of skin cancer, and SCCs make up about 90% of head and neck cancers (HNSCCs). HNSCCs harbor two frequent molecular alterations, namely, gain-of-function alterations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and loss-of-function mutations of tumor protein p53 (TP53). However, it remains poorly understood whether HNSCCs harboring different genetic alterations exhibit differential immune tumor microenvironments (TME). It also remains unknown whether PIK3CA hyperactivation and TP53 deletion can lead to SCC development spontaneously. Here, we analyzed the Cancer Genome Atlas (TCGA) datasets of HNSCCs and found that patients with both PIK3CA and TP53 alterations exhibited worse survival, significantly lower CD8 tumor infiltrating lymphocytes (TILs) and higher M0 macrophages than other controls. To better model human tumorigenesis, we deleted TP53 and constitutively activated PIK3CA in mouse keratin-15-expressing stem cells, which leads to the spontaneous development of multilineage tumors including SCCs, termed Keratin-15-p53-PIK3CA (KPPA) tumors. KPPA tumors were heavily infiltrated with myeloid-derived suppressor cells (MDSCs), with a drastically increased ratio of polymorphonuclear-MDSC (PMN-MDSC) versus monocytic-MDSC (M-MDSC). CD8 TILs expressed more PD-1 and reduced their polyfunctionality. Overall, we established a genetic model to mimic human HNSCC pathogenesis, manifested with an immunosuppressive TME, which may help further elucidate immune evasion mechanisms and develop more effective immunotherapies for HNSCCs.

scholarly journals Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma Are Molecularly Distinct

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 105
Author(s):  
Alana Sorgini ◽  
Hugh Andrew Jinwook Kim ◽  
Peter Y. F. Zeng ◽  
Mushfiq Hassan Shaikh ◽  
Neil Mundi ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Response To Therapy ◽  
The Cancer Genome Atlas ◽  
Glottic Cancer ◽  
Neural Pathways ◽  
Cancer Genome Atlas ◽  
Tcga Dataset

Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.

scholarly journals LncRNA-Associated ceRNA Network Reveals Novel Potential Biomarkers of Laryngeal Squamous Cell Carcinoma

2020 ◽  
Vol 19 ◽  
pp. 153303382098578
Author(s):  
Zhibin Jing ◽  
Sitong Guo ◽  
Peng Zhang ◽  
Zheng Liang
Keyword(s):  
Functional Analysis ◽  
Squamous Cell Carcinoma ◽  
Survival Analysis ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Cerna Network

Objective: This study aims to construct a systematic mRNA-miRNA-lncRNA network to identify novel lncRNAs and miRNAs biomarkers for laryngeal squamous cell carcinoma (LSCC). Methods: The mRNA, miRNA and lncRNA expression profiles of LSCC were obtained from Gene Expression Omnibus (GEO) database. The differentially expressed mRNAs, miRNAs and lncRNAs (DEmRNAs, DEmiRNAs and DElncRNAs) were screened between LSCC tissues and controls. Functional analysis of DEmRNAs, DEmRNAs targeted by DEmiRNAs and DEmRNAs targeted by DElncRNAs were respectively performed. The miRWalk, starbase and DIANA-LncBase were respectively used to predict DEmiRNAs-DEmRNAs, DElncRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. ceRNA network was built by DEmiRNAs-DEmRNAs and DElncRNAs-DEmiRNAs pairs. LncRNA subcellular localization was predicted using lncLocator. Using published The Cancer Genome Atlas (TCGA) and external datasets (GSE127165 and GSE133632), we also validated the expression of key DElncRNAs and DEmiRNAs in ceRNA network. The diagnostic and prognostic value of candidate genes was evaluated by ROC curve analysis and survival analysis, respectively. Results: There were 5 mRNA datasets, 3 miRNA datasets and 2 lncRNA datasets in this study. Totally, 2957 DEmRNAs, 61 DElncRNAs and 23 DEmiRNAs were identified. Functional analysis of DEmRNAs shows that they were significantly enriched in cancer-related pathways, such as DNA replication and extracellular matrix organization. There were 11 DEmiRNAs, 17 DElncRNAs and 967 DEmRNAs in the ceRNA network. Notably, up-regulated lncRNA DGCR5-down-regulated has-miR-338-3p/has-miR-139-5p pairs in this network were experimentally validated. Moreover, down-regulated AL121839.2, down-regulated LINC02147, up-regulated AC079328.2, up-regulated AC004943.2 and up-regulated HMGA2-AS1 were located in the cytoplasm. AL121839.2 and LINC02147 interacted with has-miR-1246. AC004943.2, AC079328.2 and HMGA2-AS1 targeted has-miR-3185, has-miR-3137 and has-miR-582-5p, respectively. Based on the TCGA and external datasets (GSE127165 and GSE133632), DGCR5 and AC004943.2 were significantly up-regulated while AL121839.2 and LINC02147, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p were significantly down-regulated, which were consistent with our integration analysis. DGCR5, AL121839.2, LINC02147, AC004943.2, has-miR-338-3p, has-miR-139-5p and has-miR-582-5p could predict the occurrence of LSCC. Survival analysis suggested that only, AL121839.2 has potential prognostic value for LSCC. Conclusion: This study provided novel insights into the ceRNA network and uncovered novel lncRNAs and miRNAs with diagnostic value in LSCC.

Dickkopf-1 is a novel prognostic biomarker for laryngeal squamous cell carcinoma

2014 ◽  
Vol 134 (7) ◽  
pp. 753-759 ◽  
Author(s):  
Yong Shi ◽  
Hong-Li Gong ◽  
Liang Zhou ◽  
Jie Tian ◽  
Yang Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Laryngeal Squamous Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Dickkopf 1
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