B148
Genomewide mRNA profiling of familial and non-familial esophageal squamous cell carcinoma for identification of molecular mechanism of esophageal cancer in high-risk area of India
Indranil Chattopadhyay, Avninder Singh, Sujala Kapur, Sunita Saxena
Institute of Pathology, New Delhi, India
Background
Esophageal cancer ranks as the sixth most common cancer among males and ninth most common cancer among females globally. The highest incidence of this cancer in India has been reported from Assam in the North-east region where there is wide spread use of tobacco and betel quid with fermented areca nuts. Further, familial aggregation of esophageal cancer has also been reported from this region of India. However, molecular profiling of esophageal cancer in this region has so far not been investigated.
Method
In the current study, of 317 cases of esophageal cancer reported from 2004 to 2006, 92 (29%) cases were found to have a family history of esophageal and/or other cancers. Genes and molecular functional pathways involved in familial and non-familial esophageal cancer cases were analyzed in esophageal tumour tissue by gene expression profiling using cDNA microarray and were validated by Real-Time PCR and Tissue Microarray.
Results
On the basis of Gene Ontology, MAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity were most significantly up regulated and structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, and acyl group transferase activity were most significantly down regulated in non-familial esophageal squamous cell carcinoma (ESCC) cases.
Genes involved in regulation of actin cytoskeleton (WASL), neuroactive ligand receptor interaction (GRM3), Toll-like receptor (CD14), B-cell receptor (IFITM1) and insulin signaling pathways (FOXO1A) were up- regulated and genes involved in humoral immune response (PF4), extracellular matrix organization (COL4A4), metabolism of xenobiotics (EPHX1), TGF-β signaling (SMAD1) and calcium signaling pathways (VDAC1) were down-regulated in familial ESCC cases.
Conclusion
The use of high throughput genomic technology in clinical specimens from well characterised populations that have familial clustering of cancer may lead to identification of molecular mechanism associated with progression of esophageal cancer.
