IgG Fc Binding Protein (FCGBP) is Down-Regulated in Metastatic Lesions and Predicts Survival in Metastatic Colorectal Cancer Patients

Abstract

BackgroundThe liver is the most frequent site for metastatic spread in colorectal cancer (CRC) patients, and these patients have much poorer prognosis than those without metastasis. Previous studies have shown that IgG Fc binding protein (FCGBP) plays important roles in tumorigenesis, progression, and prognosis, but its role in CRC metastasis remains unclear.PurposeIn this study, we are aimed to explore the significance of FCGBP in liver metastatic CRC (LMCRC) patients.MethodsWe analyzed the expression of FCGBP RNA between CRC primary samples and liver metastatic samples in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA). Next, we assessed the expression of FCGBP protein in 135 paired primary CRC (PC) samples and LMCRC samples. Finally, we explored the relationship between the expression features and clinicopathological characteristics.ResultsThe expression data of FCGBP were obtained from the GEO and TCGA databases. FCGBP RNA expression was evaluated between primary lesions (PC) and liver metastatic lesions (LM). FCGBP RNA was down-regulated in PC and LM, and especially lower in LM (p<0.001). Next, the expression of FCGBP protein was evaluated by an immunohistochemistry array in 135 paired primary tumor tissues and metastatic tissues. We found that FCGBP protein was down-regulated in primary lesions and metastatic lesions, especially in metastatic lesions. According to the immunohistochemistry score (SI), each cohort was divided into FCGBP-positive (SI=4–12) and FCGBP-negative (SI=0–3) groups. In both groups, the levels of CEA (PC group, 3.880 vs 77.049, p<0.001; LM group, 3.890 vs 14.239, p=0.008) and CA19-9 (PC group, 8.610 vs 111.700, p<0.001; LM group, 7.660 vs 19.380, p=0.037) were lower than those in the FCGBP-negative group. FCGBP positivity in the LM cohort was an independent risk factor in both overall survival (HR 1.573, 95% Cl [1.017–2.433], p=0.042) and disease-free survival (HR 1.869, 95% Cl [1.256–2.781], p=0.002).ConclusionThis study found a relationship between FCGBP expression and clinical information of LMCRC patients, and found that FCGBP expression decreased with disease development. The expression of FCGBP in liver metastasis is associated with both the overall and progression-free survival. Our results show that FCGBP could be a promising prognostic factor for LMCRC.