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Research Outline     

To explore the molecular biomarkers for prognosis and tumor recurrence of colorectal cancer (CRC), we have evaluated the clinical relevance of loss of heterozygosity (LOH) at different genetic loci in colorectal carcinoma and found that (1) allelic deletion of TP53-Dint marker predicts a worse survival status; (2) LOH at TP53-Penta and DCC loci are the prognostic markers for early recurrence of Dukes’ C patients. Besides, we also detected mitochondrial genomic instability (mtGI) in colorectal carcinomas and found that mtGI occurs with a high frequency in CRC and confers a better prognosis in Dukes’ C patients. On the other hand, to identify the tumor suppressor genes (TSGs) associated with CRC, we used microsatellite markers spanning from chromosome 4pter to 4qter to identify one locus at 4q27 with the highest LOH frequency of 32.9%. By performing the fine deletion mapping, we further determined a commonly deleted region with the estimated genetic length of 1.33 Mb. Importantly, deletion of this region is also correlated to the clinicopathological stage, suggesting that inactivation of a TSG(s) in the region plays a role in progression of CRC. Nowadays, three candidate TSGs are taken as the first priority to study via in vitro cell models, in vivo xenograft tumor model in SCID mice, and genetic mouse models.