Prognostic and immunological roles of Fc fragment of IgG binding protein in colorectal cancer

Abstract

Valuable diagnostic and prognostic biomarkers are urgently needed for colorectal cancer (CRC), which is one of the leading causes of mortality worldwide. Previous studies have reported altered expression of a mucin-like protein Fc fragment of IgG binding protein (FCGBP) in various types of cancer, but its potential diagnostic, prognostic and immunological roles in CRC remain to be determined. Therefore, the aim of current study was to investigate the potential roles of FCGBP in CRC. The present study investigated FCGBP mutations and changes in its expression levels using a combination of microarray and public dataset analyses, as well as immunohistochemistry. The results demonstrated a 10.5% mutation frequency in the FCGBP coding sequence in CRC tissues, and identified decreased FCGBP mRNA or protein expression levels in colorectal adenoma and CRC (compared with those in normal colorectal tissues from healthy control subjects), including pathologically advanced CRC (stage Ⅲ+Ⅳ vs. I+II). Survival analysis using the GEPIA and Kaplan-Meier Plotter databases revealed that low FCGBP expression levels were associated with short overall, disease-free, relapse-free and event-free survival times in patients with CRC. Notably, analysis using the online Tumor IMmune Estimation Resource database revealed a positive correlation between FCGBP expression levels and the extent of infiltrating immune cells, such as B cells and dendritic cells. Consistently, the expression levels of most markers (51/57) for various types of immune cells were significantly correlated with FCGBP expression levels in CRC tissues. These findings suggested that FCGBP may serve as a diagnostic and prognostic biomarker, and that FCGBP may be associated with immune infiltration in CRC.

Role of the mucin-like glycoprotein FCGBP in mucosal immunity and cancer

“…In the other work, FCGBP correlates positively with M2 macrophage polarization and negatively with M1 polarization (67). This suggests that FCGBP is also involved in regulating the infiltration of immune cells in the tumor microenvironment of ovarian cancer, where it may be a valuable marker for prognostic evaluation (67,75). In CRC, FCGBP abundance shows inverse correlation with tumor purity and macrophage expression but coincides with a high number of B cells, suggesting that FCGBP may be involved in humoral immune responses in this cancer (76).…”

“…First, the elevated expression of FCGBP may reflect pathophysiologic changes in Crohn's disease and ulcerative colitis (40), but the mRNA and protein expression of FCGBP are decreased in colorectal adenomas and cancers. Furthermore, cancer progression and the formation of metastatic lesions leads to further significant reduction (75), highlighting the role of FCGBP in oncogenesis and cancer progression. The second one is that the alternative splicing of FCGBP mRNA is detected in lung cancer (44), hepato-cholangiocarcinoma (80), CRC (75,81), and brain arteriovenous malformations (42).…”

FCGBP Is a Prognostic Biomarker and Associated With Immune Infiltration in Glioma

“…Significantly low expression of FCGBP has been observed in intestinal inflammation and tumors, such as ulcerative colitis (24), colorectal adenoma (25), and colorectal cancer (26)(27)(28). In addition, FCGBP is also down-regulated in multiple tumors (12,13,29,30), and this imbalance of expression due to different functions that may be involved in different tumors. Through the TCGA and CGGA databases, we first found that FCGBP was highly expressed in glioma tissues and had a significant positive correlation with the grade of glioma.…”

Definition of an Inflammatory Biomarker Signature in Plasma-Derived Extracellular Vesicles of Glioblastoma Patients

“…Initially reported as an important component of immunological mucosal defences [ 60 ], FCGBP gained more interest recently due to the fact of its variable expression and contradictory roles in different types of malignancies, where it seems to be involved in the immune response associated with cancer development [ 61 , 62 , 63 , 64 ]. Of note, it has been shown to be a metastasis-associated gene in IDH wild-type gliomas [ 65 ] and a tumour antigen in low-grade gliomas [ 61 ].…”