Resistance/response molecular signature for oral tongue squamous cell carcinoma
Publication Type:Journal Article
Source:Disease Markers, Volume 32, Number 1, p.51-64 (2012)
Keywords:ABC transporter G1, adult, apoptosis, ATP-Binding Cassette Transporters, Biological, cancer invasion, cancer patient, Carcinoma, clinical article, Collagen Type V, female, Fibronectins, Follow-Up Studies, Gene expression profiling, Gene Expression Regulation, Genetic Markers, high throughput screening, human, human tissue, Humans, immune response, immunohistochemistry, interleukin 8, Interleukin-8, interstitial collagenase, Local, male, Matrix Metalloproteinase 1, metastasis, middle aged, mouth carcinoma, Mouth Mucosa, Neoplasm Recurrence, Neoplastic, Predictive Value of Tests, priority journal, Prognosis, protein col5a1, protein ctsc, protein Fn1, protein hbb, protein igla, quantitative analysis, real time polymerase chain reaction, recurrent cancer, Reference Values, regulatory mechanism, Reproducibility of Results, review, Saliva, sensitivity and specificity, Squamous Cell, squamous cell carcinoma, tongue carcinoma, Tongue Neoplasms, treatment response, tumor marker, Tumor Markers, unclassified drug, validation study
Worldwide, the incidence of oral tongue cancer is on the rise, adding to the existing burden due to prevailing low survival and high recurrence rates. This study uses high-throughput expression profiling to identify candidate markers of resistance/response in patients with oral tongue cancer. Analysis of primary and post-treatment samples (12 tumor and 8 normal) by the Affymetrix platform (HG U133 plus 2) identified 119 genes as differentially regulated in recurrent tumors. The study groups had distinct profiles, with induction of immune response and apoptotic pathways in the non-recurrent and metastatic/invasiveness pathways in the recurrent group. Validation was carried out in tissues by Quantitative Real-Time PCR (QPCR) (n=30) and immunohistochemistry (IHC) (n=35) and in saliva by QPCR (n=37). The markers, COL5A1, HBB, IGLA and TSC individually and COL5A1 and HBB in combination had the best predictive power for treatment response in the patients. A subset of markers identified (COL5A1, ABCG1, MMP1, IL8, FN1) could be detected in the saliva of patients with oral cancers with their combined sensitivity and specificity being 0.65 and 0.87 respectively. The study thus emphasizes the extreme prognostic value of exploring markers of treatment resistance that are expressed in both tissue and saliva. © 2012-IOS Press and the authors. All rights reserved.
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