Leucine-rich alpha-2-glycoprotein-1 is upregulated in sera and tumors of ovarian cancer patients

Abstract

BackgroundNew biomarkers that replace or are used in conjunction with the current ovarian cancer diagnostic antigen, CA125, are needed for detection of ovarian cancer in the presurgical setting, as well as for detection of disease recurrence. We previously demonstrated the upregulation of leucine-rich alpha-2-glycoprotein-1 (LRG1) in the sera of ovarian cancer patients compared to healthy women using quantitative mass spectrometry.MethodsLRG1 was quantified by ELISA in serum from two relatively large cohorts of women with ovarian cancer and benign gynecological disease. The expression of LRG1 in ovarian cancer tissues and cell lines was examined by gene microarray, reverse-transcriptase polymerase chain reaction (RT-PCR), Western blot, immunocytochemistry and mass spectrometry.ResultsMean serum LRG1 was higher in 58 ovarian cancer patients than in 56 healthy women (89.33 ± 77.90 vs. 42.99 ± 9.88 ug/ml; p = 0.0008) and was highest among stage III/IV patients. In a separate set of 193 pre-surgical samples, LRG1 was higher in patients with serous or clear cell ovarian cancer (145.82 ± 65.99 ug/ml) compared to patients with benign gynecological diseases (82.53 ± 76.67 ug/ml, p < 0.0001). CA125 and LRG1 levels were moderately correlated (r = 0.47, p < 0.0001). LRG1 mRNA levels were higher in ovarian cancer tissues and cell lines compared to their normal counterparts when analyzed by gene microarray and RT-PCR. LRG1 protein was detected in ovarian cancer tissue samples and cell lines by immunocytochemistry and Western blotting. Multiple iosforms of LRG1 were observed by Western blot and were shown to represent different glycosylation states by digestion with glycosidase. LRG1 protein was also detected in the conditioned media of ovarian cancer cell culture by ELISA, Western blotting, and mass spectrometry.ConclusionsSerum LRG1 was significantly elevated in women with ovarian cancer compared to healthy women and women with benign gynecological disease, and was only moderately correlated with CA125. Ovarian cancer cells secrete LRG1 and may contribute directly to the elevated levels of LRG1 observed in the serum of ovarian cancer patients. Future studies will determine whether LRG1 may serve as a biomarker for presurgical diagnosis, disease recurrence, and/or as a target for therapy.

LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway

“…Although potential clinicopathologic associations have been demonstrated with LRG1 in multiple tumors, including ovarian (Andersen et al, 2010), lung (Li et al, 2011) and colon cancer (Ladd et al, 2012), little is known about the role of LRG1 in tumor cells and tumor development. In this study, we observed that LRG1 was highly expressed in Grade IV glioma cell lines, but was expressed at a relatively lower level in SHG-44 cells (F) Immunofluorescence staining was performed to observe the distribution of E-cadherin protein in glioma cells.…”

Identification of O-glycosylated Proteins That Are Aberrantly Excreted in the Urine of Patients with Early Stage Ovarian Cancer

“…It is mainly produced by the liver cells in response to cancer, but its synthesis by OCa cells has also been documented [11]. The actual functions of LRG are still unknown, although the glycoprotein has been associated with cell adhesion, granulocytic differentiation, cell migration, cell survival, protein interaction and signal transduction [12]. The O -glycosylated protein was also proposed to be involved in the acute-phase response, since its level was reported to be elevated in patients with microbial infection, as well as those afflicted with several different cancers, including OCa [11].…”

Overexpression of leucine‐rich α2‐glycoprotein‐1 is a prognostic marker and enhances tumor migration in gastric cancer

“…The expression of LRG1 is elevated in the sera of patients with autoimmune diseases such as Crohn's disease, ulcerative colitis, and rheumatoid arthritis, and it is correlated with the disease status . Furthermore, recent studies have reported that LRG1 can be used as a biomarker in several types of cancer such as ovarian, lung, biliary tract, and hepatocellular carcinoma . Serum LRG1 is also detected in patients with malignancies and associated with progression of malignancies .…”