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. 2019 May 3;10:865.
doi: 10.3389/fimmu.2019.00865. eCollection 2019.

Is the Complement Protein C1q a Pro- Or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas

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Free PMC article

Is the Complement Protein C1q a Pro- Or Anti-tumorigenic Factor? Bioinformatics Analysis Involving Human Carcinomas

Alessandro Mangogna et al. Front Immunol. .
Free PMC article

Abstract

C1q is the first subcomponent of the classical pathway of the complement system and belongs to the C1q/Tumor Necrosis Factor superfamily. C1q can perform a diverse range of immune and non-immune functions in a complement-dependent as well as -independent manner. Being a pattern recognition molecule of the innate immunity, C1q can recognize a number of self, non-self and altered-self ligands and bring about effector mechanisms designed to clear pathogens via opsonisation and inflammatory response. C1q is locally synthesized by macrophages and dendritic cells, and thus, can get involved in a range of biological processes, such as angiogenesis and tissue remodeling, immune modulation, and immunologic tolerance. The notion of C1q involvement in the pathogenesis of cancer is still evolving. C1q appears to have a dual role in cancer: tumor promoting as well as tumor-protective, depending on the context of the disease. In the current study, we performed a bioinformatics analysis to investigate whether C1q can serve as a potential prognostic marker for human carcinoma. We used the Oncomine database and the survival analysis platforms Kaplan-Meier plotter. Our results showed that high levels of C1q have a favorable prognostic index in basal-like breast cancer for disease-free survival, and in HER2-positive breast cancer for overall survival, while it showed a pro-tumorigenic role of C1q in lung adenocarcinoma, and in clear cell renal cell carcinoma. This in silico study, if validated via a retrospective study, can be a step forward in establishing C1q as a new tool as a prognostic biomarker for various carcinoma.

Keywords: C1q; classical pathway; complement; microenvironment; prognosis; tumor.

Figures

Graphical Abstract
Graphical Abstract
Summary of the conclusions of the study.
Figure 1
Figure 1
C1QA, C1QB, and C1QC expression in invasive breast carcinoma. Curtis's datasets were used for bioinformatics analysis to explore C1QA and C1QB mRNAs expression in the breast cancer, whereas Perou's datasets was used for bioinformatics analysis to evaluate C1QC mRNA. A higher C1q mRNAs expression was detectable in invasive breast carcinoma compared to normal breast tissue (A). The analysis of the different breast carcinoma histotypes by Finak's dataset revealed how the medullary breast cancer presented the major intensity of C1q mRNA expression (B). According to the data Kaplan-Meir plotter, C1QA, C1QB, and C1QC mRNA expressions was positively linked to a disease-free survival (DFS) rate in patients with basal-like cancers (C) (p<0.05) and to an overall survival (OS) rate with HER-2 positive cancers (Supplementary Table 2). HR, hazard ratio.
Figure 2
Figure 2
Immunohistochemistry analysis for C1q in breast (A), kidney (B) and lung carcinoma (C). Representative microphotographs showing expression of C1q in different carcinoma. The expression of C1q in carcinoma was observed in all tissues with differential distribution in the TME, as described in the result section. DAB (brown) chromogen was used to visualize the binding of anti-human C1q antibodies; scale bars, 50μm.
Figure 3
Figure 3
Pathological significance of C1q expression kidney and in lung cancer. Gumz's dataset have explored C1QA and C1QB mRNA expression in kidney, whereas Higgins' dataset were used for C1QC mRNA expression. A higher C1q expression was detectable in CCRCC cancer than that in normal tissue (A), p < 0.05. According to the data from Kaplan-Meier plotter, C1q mRNA expressions were negatively related to an overall survival rate of the patients with CCRCC (B). HR, hazard ratio. Selamat's dataset have revealed a lower C1QA and C1QC mRNA expression in lung adenocarcinoma that in normal lung tissues (C), whereas Bhattacharjiee's dataset was used for C1QB, but the results were in accordance with Selamat's one. There was a negative association between C1q mRNA expression and a favorable prognosis in patients with lung cancer, for Kaplan-Meir plotter (D). HR, hazard ratio.

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