TY - JOUR
T1 - Post-operative plasma osteopontin predicts distant metastasis in human colorectal cancer
AU - Ng, Lui
AU - Wan, Timothy Ming Hun
AU - Lam, Colin Siu Chi
AU - Chow, Ariel Ka Man
AU - Wong, Sunny Kit Man
AU - Man, Johnny Hon Wai
AU - Li, Hung Sing
AU - Cheng, Nathan Shiu Man
AU - Pak, Ryan Chung Hei
AU - Cheung, Alvin Ho Kwan
AU - Yau, Thomas Chung Cheung
AU - Lo, Oswens Siu Hung
AU - Foo, Dominic Chi Chung
AU - Poon, Jensen Tung Chung
AU - Poon, Ronnie Tung Ping
AU - Pang, Roberta Wen Chi
AU - Law, Wai Lun
N1 - Publisher Copyright:
© 2015 Ng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2015/5/11
Y1 - 2015/5/11
N2 - Background: 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. Methods: 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. Results: 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, postoperative 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. Conclusions: 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.
AB - Background: 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. Methods: 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. Results: 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, postoperative 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. Conclusions: 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.
UR - http://www.scopus.com/inward/record.url?scp=84930617546&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0126219
DO - 10.1371/journal.pone.0126219
M3 - Article
C2 - 25961724
AN - SCOPUS:84930617546
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e0126219
ER -
