LMX1B mRNA expression and its gene body CpG methylation are valuable prognostic biomarkers for laryngeal squamous cell carcinoma

Abstract Several members of the family of tissue kallikrein and kallikrein-related peptidases have been suggested as promising tumor biomarkers with important prognostic significance. However, only one (KLK11) has already been studied in laryngeal squamous cell carcinoma (LSCC) as a potential biomarker for LSCC diagnosis and/or prognosis. Our study investigated the prognostic value of kallikrein-related peptidase-4 (KLK4) mRNA expression as a molecular tissue biomarker in LSCC. For this purpose, KLK4 mRNA expression analysis was performed in 116 cancerous and 74 paired non-cancerous laryngeal tissue specimens obtained from patients that had undergone surgical treatment for primary LSCC. A remarkable downregulation of KLK4 mRNA expression was discovered in laryngeal tumors, compared to non-cancerous laryngeal tissue specimens. KLK4 mRNA expression was also shown to distinguish LSCC from non-cancerous laryngeal tissues. Furthermore, low KLK4 mRNA expression was shown to predict poor disease-free survival, independently of the histological grade and size of the malignant tumor as well as patient TNM stage. According to Kaplan-Meier survival analysis, low KLK4 mRNA expression predicts short-term relapse even among patients with well-differentiated tumors or those at an early TNM stage. Thus, KLK4 mRNA positivity could be regarded as a novel independent indicator of favorable prognosis for the disease-free survival of LSCC patients.

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Interleukin-4 mRNA Expression in Laryngeal Squamous Cell Carcinoma Patients with or without Lymph Node Involvement

Galen Medical Journal ◽

10.31661/gmj.v3i1.159 ◽

2014 ◽

Vol 3 (1) ◽

pp. 20-23

Author(s):

Esmael Amirazodi ◽

Mahboobeh Razmkhah ◽

Mansoureh Jaberipour ◽

Ahmad Hosseini ◽

Bijan Khademi

Keyword(s):

Squamous Cell Carcinoma ◽

Lymph Node ◽

Cell Carcinoma ◽

Mrna Expression ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Lymph Node Involvement ◽

Interleukin 4 ◽

Node Positive ◽

Lymph Node Positive

Background: Interleukin (IL)-4 is a member of T helper 2 (Th2) axis produced by T-lymphocyte and mast cell. It has been shown that IL-4 expression changes in tumor tissues. The main objective of this study is to investigate the expression of IL-4 mRNA in patients with Laryngeal Squamous Cell Carcinoma (LSCC) with or without lymph node involvement.Materials and Methods: mRNA expression of IL-4 in LSCC tissues were detected by quantative Real-Time PCR (qRT-PCR). Expression of IL-4 gene was compared between lymph node positive and negative patients with Squamous Cell Carcinoma of Larynx.Results: No statistically significant association was found in expression of IL-4 between lymph node positive and negative patients. Conclusion: It seems that IL-4 has no important effect on the involvement of lymph node in LSCC. However, to achieve a definite conclusion more investigations are certainly required.

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

Journal of International Medical Research ◽

10.1177/0300060520919252 ◽

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.

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Integrated Analysis of Long Noncoding RNA and mRNA Expression Profile in Advanced Laryngeal Squamous Cell Carcinoma

PLoS ONE ◽

10.1371/journal.pone.0169232 ◽

2016 ◽

Vol 11 (12) ◽

pp. e0169232 ◽

Cited By ~ 31

Author(s):

Ling Feng ◽

Ru Wang ◽

Meng Lian ◽

Hongzhi Ma ◽

Ning He ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Mrna Expression ◽

Expression Profile ◽

Squamous Cell ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Laryngeal Squamous Cell Carcinoma ◽

Integrated Analysis ◽

Mrna Expression Profile

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Combined detection of serum exosomal miR-21 and HOTAIR as diagnostic and prognostic biomarkers for laryngeal squamous cell carcinoma

Medical Oncology ◽

10.1007/s12032-014-0148-8 ◽

2014 ◽

Vol 31 (9) ◽

Cited By ~ 112

Author(s):

Jingting Wang ◽

Yandong Zhou ◽

Jianguang Lu ◽

Yanan Sun ◽

Hui Xiao ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Prognostic Biomarkers ◽

Combined Detection

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lncRNA TMEM51-AS1 and RUSC1-AS1 function as ceRNAs for induction of laryngeal squamous cell carcinoma and prediction of prognosis

PeerJ ◽

10.7717/peerj.7456 ◽

2019 ◽

Vol 7 ◽

pp. e7456 ◽

Cited By ~ 3

Author(s):

Lian Hui ◽

Jing Wang ◽

Jialiang Zhang ◽

Jin Long

Keyword(s):

Squamous Cell Carcinoma ◽

Regression Analysis ◽

Cell Carcinoma ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Cox Regression ◽

Negative Relationship ◽

Prognostic Biomarkers ◽

Cox Regression Analysis ◽

Cerna Network

Background Long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to interact with miRNAs to regulate target genes and promote cancer initiation and progression. The expression of lncRNAs and miRNAs can be epigenetically regulated. The goal of this study was to construct an lncRNA-miRNA-mRNA ceRNA network in laryngeal squamous cell carcinoma (LSCC) and reveal their methylation patterns, which was not investigated previously. Methods Microarray datasets available from the Gene Expression Omnibus database were used to identify differentially expressed lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between LSCC and controls, which were then overlapped with differentially methylated regions (DMRs). The ceRNA network was established by screening the interaction relationships between miRNAs and lncRNAs/mRNAs by corresponding databases. TCGA database was used to identify prognostic biomarkers. Results Five DELs (downregulated: TMEM51-AS1, SND1-IT1; upregulated: HCP5, RUSC1-AS1, LINC00324) and no DEMs were overlapped with the DMRs, but only a negative relationship occurred in the expression and methylation level of TMEM51-AS1. Five DELs could interact with 11 DEMs to regulate 242 DEGs, which was used to construct the ceRNA network, including TMEM51-AS1-miR-106b-SNX21/ TRAPPC10, LINC00324/RUSC1-AS1-miR-16-SPRY4/MICAL2/ SLC39A14, RUSC1-AS1-miR-10-SCG5 and RUSC1-AS1-miR-7-ZFP1 ceRNAs axes. Univariate Cox regression analysis showed RUSC1-AS1 and SNX21 were associated with overall survival (OS); LINC00324, miR-7 and ZFP1 correlated with recurrence-free survival (RFS); miR-16, miR-10, SCG5, SPRY4, MICAL2 and SLC39A14 were both OS and RFS-related. Furthermore, TRAPPC10 and SLC39A14 were identified as independent OS prognostic factors by multivariate Cox regression analysis. Conclusion DNA methylation-mediated TMEM51-AS1 and non-methylation-mediated RUSC1-AS1 may function as ceRNAs for induction of LSCC. They and their ceRNA axis genes (particularly TMEM51-AS1-miR-106b-TRAPPC10; RUSC1-AS1-miR-16-SLC39A14) may be potentially important prognostic biomarkers for LSCC.

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Integrated miRNA and mRNA expression analysis uncovers drug targets in laryngeal squamous cell carcinoma patients

Oral Oncology ◽

10.1016/j.oraloncology.2019.04.018 ◽

2019 ◽

Vol 93 ◽

pp. 76-84 ◽

Cited By ~ 8

Author(s):

Rainer Marco Lopez Lapa ◽

Mateus Camargo Barros-Filho ◽

Fabio Albuquerque Marchi ◽

Maria Aparecida Custódio Domingues ◽

Genival Barbosa de Carvalho ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Mrna Expression ◽

Expression Analysis ◽

Squamous Cell ◽

Drug Targets ◽

Laryngeal Squamous Cell Carcinoma ◽

Mrna Expression Analysis

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The clinical significance of interleukin 24 and its potential molecular mechanism in laryngeal squamous cell carcinoma

Cancer Biomarkers ◽

10.3233/cbm-201441 ◽

2020 ◽

Vol 29 (1) ◽

pp. 111-124

Author(s):

Xiao-Zhun Tang ◽

Xian-Guo Zhou ◽

Xiao-Guohui Zhang ◽

Guo-Sheng Li ◽

Gang Chen ◽

...

Keyword(s):

Extracellular Matrix ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Mrna Expression ◽

Clinical Significance ◽

Squamous Cell ◽

Laryngeal Squamous Cell Carcinoma ◽

Receptor Interaction ◽

Ppi Networks ◽

Standard Mean Difference

Interleukin 24 (IL24) has been documented to be highly expressed in several cancers, but its role in laryngeal squamous cell carcinoma (LSCC) remains unclarified. In this study, to reveal the function and its clinical significance of IL24 in LSCC, multiple detecting methods were used comprehensively. IL24 protein expression was remarkably higher in LSCC (n= 49) than non-cancerous laryngeal controls (n= 26) as detected by in-house immunohistochemistry. Meanwhile, the IL24 mRNA expression was also evaluated based on high throughput data from Gene Expression Omnibus, The Cancer Genome Atlas, ArrayExpress and Oncomine databases. Consistently with the protein level, IL24 mRNA expression level was also predominantly upregulated in LSCC (n= 172) compared to non-cancerous laryngeal tissues (n= 81) with the standard mean difference (SMD) being 1.25 and the area under the curve (AUC) of the summary receiver operating characteristic (sROC) being 0.89 (95% CI = 0.86–0.92). Furthermore, the related genes of IL24 and the differentially expressed genes (DEGs) of LSCC were intersected and sent for Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and the protein-protein interaction (PPI) analyses. In the GO annotation, the top terms of biological process (BP), cellular component (CC) and molecular function (MF) were extracellular matrix organization, extracellular matrix, cytokine activity, respectively. The top pathway of KEGG was ECM-receptor interaction. The PPI networks indicated the top hub genes of IL24-related genes in LSCC were SERPINE1, TGFB1, MMP1, MMP3, CSF2, and ITGA5. In conclusion, upregulating expression of IL24 may enhance the occurrence of LSCC, which owns prospect diagnostic ability and therapeutic significance in LSCC.

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