OncoTargets and Therapy (May 2018)
Leucine-rich alpha-2-glycoprotein-1 is up-regulated in colorectal cancer and is a tumor promoter
Abstract
Qian Zhang,1,2 Rui Huang,1,2 Qingchao Tang,1,2 Yang Yu,1,2 Quanlong Huang,1,2 Yinggang Chen,1,2 Guiyu Wang,1,2 Xishan Wang2,3 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; 2Colorectal Cancer Center, Colorectal Cancer Institute of Harbin Medical University, Harbin, China; 3Department of Colorectal Surgery, Cancer Hospital of Chinese Academy of Medical Science, Beijing, China Background: Leucine-rich α-2-glycoprotein-1 (LRG1) is differentially expressed in many kinds of diseases including cancer, however, it has not been thoroughly studied yet. Purpose: The objective of this study was to detect the expression and potential mechanism of LRG1 in colorectal cancer (CRC). In our study, we examined LRG1 levels in CRC tissue and plasma with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The effect of LRG1 on cancer cells was detected with transwell and MTT assays. Results: The average plasma LRG1 level in CRC was significantly higher than in polyp group (P=0.002) and healthy controls (P<0.001). Second, plasma LRG1 was positively associated with CA19-9 (r=0.133, P=0.039) and neutrophil ratio (r=0.403, P<0.001). Third, plasma LRG1 of stage IV patients was dramatically different from that of stage I, stage II or stage III patients (P<0.001). LRG1 mRNA expression levels were about 2-fold higher in CRCs compared to normal tissues (P<0.001). And levels of plasma LRG1 were found to be a risk factor in CRC in univariate survival analysis of colorectal prognosis (P=0.013, hazard ratio [HR]=1.803, 95% CI: 1.521–2.137), and multivariate analysis showed that LRG1 was an independent risk factor (P<0.001, HR=1.492, 95% CI: 1.223–1.820). The patients with higher plasma LRG1 value presented with poorer outcome (P=0.013). Functional experiments showed that LRG1 could promote the invasion and growth ability of cells. LRG1 was increased in plasma and tissue compared with that of controls and LRG1 may predict prognosis of CRC patients and LRG1 maybe a tumor promoter. Conclusion: LRG1 is increased in CRC patients and might serve as a tumor promoter. Keywords: adenomatous polyps, CA19-9 antigen, colorectal neoplasms, leucine-rich alpha-2-glycoprotein, prognosis, tumor promoter
