Clinical relevance of nine transcriptional molecular markers for the diagnosis of head and neck squamous cell carcinoma in tissue and saliva rinse

Abstract

BackgroundAnalysis of 23 published transcriptome studies allowed us to identify nine genes displaying frequent alterations in HNSCC (FN1, MMP1, PLAU, SPARC, IL1RN, KRT4, KRT13, MAL, and TGM3). We aimed to independently confirm these dysregulations and to identify potential relationships with clinical data for diagnostic, staging and prognostic purposes either at the tissue level or in saliva rinse.MethodsFor a period of two years, we systematically collected tumor tissue, normal matched mucosa and saliva of patients diagnosed with primary untreated HNSCC. Expression levels of the nine genes of interest were measured by RT-qPCR in tumor and healthy matched mucosa from 46 patients. MMP1 expression level was measured by RT-qPCR in the salivary rinse of 51 HNSCC patients and 18 control cases.ResultsDysregulation of the nine genes was confirmed by the Wilcoxon test. IL1RN, MAL and MMP1 were the most efficient diagnostic markers of HNSCC, with ROC AUC > 0.95 and both sensitivity and specificity above 91%. No clinically relevant correlation was found between gene expression level in tumor and T stage, N stage, tumor grade, global survival or disease-free survival. Our preliminary results suggests that with 100% specificity, MMP1 detection in saliva rinse is potentially useful for non invasive diagnosis of HNSCC of the oral cavity or oropharynx, but technical improvement is needed since sensitivity was only 20%.ConclusionIL1RN, MAL and MMP1 are prospective tumor diagnostic markers for HNSCC. MMP1 overexpression is the most promising marker, and its detection could help identify tumor cells in tissue or saliva.

KRT13, FAIM2 and CYP2W1 mRNA Expression in Oral Squamous Cell Carcinoma Patients with Risk Habits

“…In the present study, KRT13 showed significantly down-regulated in OSCC as compared with non-OSCC. This finding was in concordance with a study by Lallemant et al (2009) using qPCR assay which concurred that KRT13 expression was found lower in the head and neck cancer tumour tissues as compared with normal tissues. In the immunohistochemical studies, KRT13 was 100% expressed in normal mucosa, mild and moderate oral epithelial dysplasia.…”

Differential Expression of Cytokeratin 13 in Non-Neoplastic, Dysplastic and Neoplastic Oral Mucosa in a High Risk Pakistani Population

“…In some studies quantitative real-time PCR method was used to demonstrate considerable down-regulation of KRT13 gene in OSCC samples as compared with non-OSCC sample (Lallemant et al, 2009;Hiroko et al, 2012;Firstine et al, 2015).…”

Loss of nuclear expression of Krüppel-like factor 4 is associated with poor prognosis in patients with oral cancer

“…Surgical resection combined with radiotherapy/chemotherapy is currently the primary treatment strategy, but the therapeutic effect remains unsatisfactory, and patients have a poor 5-year survival rate [2]. Some molecular markers of oral cancer have been proposed, but the unequivocal prognostic and/or predictive significance of the markers has not been established [3][4][5][6][7][8]. A prognostic marker that could act as a therapeutic target could potentially be used to develop new and effective treatment strategies for oral cancer.…”