Journal Article

Post-Operative Plasma Osteopontin Predicts Distant Metastasis in Human Colorectal Cancer

Poon, Jensen Tung-Chung, Wan, Timothy Ming-Hun, Lam, Colin Siu-Chi, Man, Johnny Hon-Wai, Poon, Ronnie Tung-Ping, Chow, Ariel Ka-Man, Pang, Roberta Wen-Chi, Cheng, Nathan Shiu-Man, Wong, Sunny Kit-Man, Yau, Thomas Chung-Cheung, Cheung, Alvin Ho-Kwan, Law, Wai-Lun, Ng, Lui, Pak, Ryan Chung-Hei, Lo, Oswens Siu-Hung, Foo, Dominic Chi-Chung, Li, Hung-Sing

2015

Overview

The overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients. This randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay. Our findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration. The results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Analysis / Biocompatibility / Biomarkers / Biomarkers, Tumor - blood / Biomedical materials / Breast cancer / Cancer / Cancer metastasis / Care and treatment / Cell Line, Tumor / Cell migration / Chemotherapy / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - blood / Colorectal Neoplasms - complications / Colorectal Neoplasms - pathology / Colorectal Neoplasms - surgery / Correlation / Correlation analysis / Development and progression / E-cadherin / Ectopic expression / Enzyme-Linked Immunosorbent Assay / Genetic aspects / Humans / Liver cancer / Lung cancer / Medical prognosis / Medical research / Medicine / Metastases / Metastasis / Neoplasm Metastasis / Oncology / Osteopontin / Osteopontin - blood / Patient outcomes / Patients / Plasma / Plasma levels / Postoperative Period / Prognosis / Prostate / Proteins / Regulators / Studies / Surgery