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


METHODS
For 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.


RESULTS
Dysregulation 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%.


CONCLUSIONS
IL1RN, 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.
Lallemant
Benjamin
B
Service d'ORL et Chirurgie Maxillo-faciale, Centre Hospitalier Universitaire de Nîmes, Place du Pr, Robert Debré, 30029 Nîmes Cedex 9, France. benjamin.lallemant@chu-nimes.fr
Evrard
Alexandre
A
Combescure
Christophe
C
Chapuis
Heliette
H
Chambon
Guillaume
G
Raynal
Caroline
C
Reynaud
Christophe
C
Sabra
Omar
O
Joubert
Dominique
D
Hollande
Frédéric
F
Lallemant
Jean-Gabriel
JG
Lumbroso
Serge
S
Brouillet
Jean-Paul
JP
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012463:Saliva / Q000737:chemistry* / Q000378:metabolism; D014158:Transcription, Genetic
D014408:Biomarkers, Tumor