Clinical Significance of G Protein-Coupled Receptor 110 (GPR110) as a Novel Prognostic Biomarker in Osteosarcoma

Abstract

BACKGROUND G protein-coupled receptor 110 (GPR110) belongs to the subfamily of the adhesion G protein-coupled receptors (GPCRs). The potential role of GPR110 has been correlated with cancer cell invasion in some tumors such as glioma. However, its expression and role in human osteosarcoma has not been identified. This study aimed to examine the expression level of GPR110 and determine whether the expression of GPR110 was correlated with aggressive clinicopathological characteristics and prognosis of osteosarcoma. MATERIAL AND METHODS This retrospective study included 94 osteosarcoma patients. Immunohistochemistry staining and quantitative real-time polymerase chain reaction were performed to detect the expression level of GPR110 in osteosarcoma specimens. We then determined the correlation of the GPR110 expression with the clinicopathological characteristics and prognosis by univariate or multivariate analysis. Patient outcomes were evaluated using the Kaplan-Meier log-rank test and prognostic factors were detected by multivariate analysis. The function of GPR110 on cell proliferation, migration, and invasion were examined in this in vitro study. RESULTS Overexpression of GPR110 was correlated with the advanced stage of osteosarcoma. Patients with high expression level of GPR110 had significantly poorer 5-year overall survival; the multivariate analysis found that GPR110 expression level can act as an independent prognosis factor. Knockdown of GPR110 can decrease the proliferation, migration, and invasion capacity of human osteosarcoma cell lines. CONCLUSIONS Our studies suggest a role of GPR110 in tumor progression and as a potential novel prognostic biomarker in osteosarcoma.

Figure 1

Analysis of GPR110 expression in human osteosarcoma. (A, B) Immunohistochemistry staining of GPR110 in human osteosarcoma without or with metastasis. (C) Staining score of the protein expression level of GPR110 in A and B. (D) Relative mRNA level of GPR110 in M0 and M1 tumor of human osteosarcoma. The M1 means the results were derived from tumor tissues with distant metastasis, therefore representing high aggressive tumors. The M0 means the results were from tumor tissues without distant metastasis, therefore representing less aggressive tumors.

Figure 2

The Kaplan-Meier curves of the overall survival of osteosarcoma patients. The overall survival time of osteosarcoma patients was evaluated by Kaplan-Meier and log-rank test, based on entire cohort (A), age (B), gender (C), tumor diameter (D), tumor location (E), tumor grade (F), distant metastasis (G), and GPR110 expression levels (H). * P<0.05 by log-rank test.

Figure 3

GPR110 promotes proliferation, migration, and invasion capacity of osteosarcoma cell lines. (A, B) Western blot results showed transfection efficiency of pcDNA3.1-GPR110 plasmids and GPR110-siRNA in SAOS-2 and K7M2 cells. (C–H) Overexpression of GPR110 enhanced the proliferation, migration, and invasion capacity of SAOS-2 and K7M2 cell lines, whereas knockdown of GPR110 inhibited cell proliferation, migration, and invasion. Student’s t-test was used to compare the differences between tested groups with “Blank” group. * indicates statistical significance (P<0.05) between tested group with “Blank” group.