Invited Speaker

Leptin Receptor Expression in Middle Eastern Colorectal Cancer and its Potential Clinical Implication.
Khawla S. Al-Kuraya, Prashant Bavi, Shahab Uddin, Nasser Al-Sanea, Alaa Abduljabbar, Luai H. Ashari, Samar Alhomoud, Fouad Al-Dayel
Saudi Arabia

We investigated the role of leptin receptor (Ob-R) and its relationship with PI3K/AKT activation in colorectal carcinomas (CRC) tissues followed by in vitro studies using a panel of CRC cell lines. Obesity serves an important risk factor of several cancers including CRC which ranks as the second most common cancer in Saudi Arabia. High levels of adipokine leptin and its Ob-R are seen in obesity and also in various carcinomas including CRC. We investigated the proliferative and antiapoptotic effect of leptin on human CRC cell lines Caco-2, HT-29 and SW-840 and the role of PI3K/AKT signaling pathway in mediating these actions. Then the expression of Ob-R and its relationship with clinicopathological features was analyzed in 448 CRC, 229 normal colon mucosa and 24 colorectal adenomas using tissue microarray technology. Treatment with leptin resulted in increased proliferation of CRC cell lines and involved activation of PI3K/AKT signaling pathway. Pretreatment with Ob-R siRNA or PI3K inhibitor inhibited these responses. Ob-R was significantly over expressed in primary CRC relative to adenomas and normal colonic mucosa. In primary CRC, Ob-R significantly correlated with leptin expression, early stage and well differentiated tumors. Intriguingly, patient with Ob-R positive tumors showed significantly better overall survival (p=0.0098). Leptin plays a critical role in CRC carcinogenesis through PI3K/AKT pathway via Ob-R. Ob-R is a prognostic marker associated with better survival