Resistance/response molecular signature for oral tongue squamous cell carcinoma.
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.
Head and Neck Oncology Services, Mazumdar Shaw Cancer Centre, Narayana Hrudayalaya Foundations, Bangalore, India.
Amritha
A
Suresh
Muhil
M
Vannan
Dhanya
D
Kumaran
Zeynep H
ZH
Gümüs
Priya
P
Sivadas
Elango Erode
EE
Murugaian
Vikram
V
Kekatpure
Subramanian
S
Iyer
Kumarasamy
K
Thangaraj
Moni Abraham
MA
Kuriakose
D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy*; D024062:Collagen Type V / Q000235:genetics; D005353:Fibronectins / Q000235:genetics; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D008875:Middle Aged; D009061:Mouth Mucosa / Q000502:physiology; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D011237:Predictive Value of Tests; D012016:Reference Values; D015203:Reproducibility of Results; D012463:Saliva / Q000502:physiology; D014062:Tongue Neoplasms / Q000235:genetics* / Q000628:therapy*
C419353:ABCG1 protein, human; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; C530725:COL5A1 protein, human; D024062:Collagen Type V; C067625:FN1 protein, human; D005353:Fibronectins; D005819:Genetic Markers; D016209:Interleukin-8; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1