A Candidate Prognostic Biomarker Complement Factor I Promotes Malignant Progression in Glioma.

Xiaomin Cai,Shuang Feng,Wenjin Qiu,Mengshu Qian,Chenghao Peng,Jiale Zhang,Yuhai Wang,Yi Wang

doi:10.3389/fcell.2020.615970

Abstract

Objectives: Glioma is the most common and aggressive type of primary central nervous system (CNS) tumor in adults and is associated with substantial mortality rates. The aim of our study was to evaluate the prognostic significance and function of the complement factor I (CFI) in glioma.Materials and Methods: The expression levels of CFI in glioma tissues and the survival of the CFIhigh and CFIlow patient groups were analyzed using The Cancer Genome Atlas (TCGA) database and Genotype-Tissue Expression (GTEx). The correlation between CFI expression and clinicopathological features of glioma was determined by univariate and multivariate Cox regression analyses in the Chinese Glioma Genome Atlas (CGGA) database. The functional role of CFI in glioma was established through routine in vitro and in vivo assays.Results: CFI is overexpressed in glioma and its high levels correlated with poor outcomes in both TCGA and CGGA datasets. Furthermore, CFI was identified as an independent prognostic factor of glioma in the CGGA database. CFI knockdown in glioma cell lines inhibited growth in vitro and in vivo, whereas its ectopic expression increased glioma cell proliferation, migration, and invasion in vitro. CFI protein levels were also significantly higher in the glioma tissues resected from patients and correlated to worse prognosis.Conclusions: CFI is a potential prognostic biomarker in glioma and drives malignant progression.

Highlights

Gliomas are the most common and aggressive type of primary central nervous system (CNS) tumor in adults (Furnari et al, 2007; Ostrom et al, 2014; Lapointe et al, 2018)
complement factor I (CFI) is overexpressed in glioma and its high levels correlated with poor outcomes in both The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets
We analyzed the CFI expression profile across diverse tumors in TCGA database and found that CFI was significantly overexpressed in COAD, glioblastoma multiform (GBM), low-grade glioma (LGG), READ, STAD, and THCA relative to the corresponding normal samples (Figure 1A)

Summary

Introduction

Gliomas are the most common and aggressive type of primary central nervous system (CNS) tumor in adults (Furnari et al, 2007; Ostrom et al, 2014; Lapointe et al, 2018). Given the molecular heterogeneity of gliomas, it is necessary to identify novel prognostic biomarkers and therapeutic targets (Hoshide and Jandial, 2016; Louis et al, 2016). The complement system plays a crucial role in the immune response against pathogens by augmenting the ability of antibodies and phagocytes to clear microbes and damaged cells (Merle et al, 2015; Afshar-Kharghan, 2017). It consists of plasma proteins, secreted from the liver, as well as cell membranebound proteins that opsonize pathogens and induce a series of inflammatory responses (Kolev et al, 2014; Yu et al, 2014; Morgan et al, 2016). A myriad of soluble membrane-bound inhibitory molecules control the complement cascade and minimize the destructive effects of aberrant complement activation

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