Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma

Abstract

The tumor microenvironment (TME) has important effects on the tumorigenesis and development of osteosarcoma (OS). However, the dynamic mechanism regulating TME immune and matrix components remains unclear. In this study, we collected quantitative data on the gene expression of 88 OS samples from The Cancer Genome Atlas (TCGA) database and downloaded relevant clinical cases of OS from the TARGET database. The proportions of tumor-infiltrating immune cells (TICs) and the numbers of immune and matrix components were determined by CIBERSORT and ESTIMATE calculation methods. Protein-protein interaction (PPI) network construction and Cox regression analysis were conducted to analyze differentially expressed genes (DEGs). The complement components C1qA, C1qB and C1qC were then determined to be predictive factors through univariate Cox analysis and PPI cross analysis. Further analysis found that the levels of C1qA, C1qB and C1qC expression were positively linked to OS patient survival time and negatively correlated with the clinicopathological feature percent necrosis at definitive surgery. The results of gene set enrichment analysis (GSEA) demonstrated that genes related to immune functions were significantly enriched in the high C1qA, C1qB and C1qC expression groups. Proportion analysis of TICs by CIBERSORT showed that the levels of C1qA, C1qB and C1qC expression were positively related to M1 and M2 macrophages and CD8+ cells and negatively correlated with M0 macrophages. These results further support the influence of the levels of C1qA, C1qB and C1qC expression on the immune activity of the TME. Therefore, C1qA, C1qB and C1qC may be potential indicators of remodeling in the OS TME, which is helpful to predict the prognosis of patients with OS and provide new ideas for immunotherapy for OS.

A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients

“…6, 11, 12 In a previous study, sarcoma was also classified in the group in which stronger expression of the classical and alternative pathway genes was associated with longer survival ( Roumenina et al, 2019 ). In a recent analysis, complement classical pathway genes C1QA, C1QB, C1QC were proved to be protective factors for survival in osteosarcoma ( Chen et al, 2021 ). The results have suggested that while the lectin pathway facilitates progression and immunosuppression of sarcoma ( Magrini et al, 2021 ), the classical pathway might have played more of a tumoricidal role and thus benefits patients’ survival.…”

Identification of hub genes and transcription factors in patients with rheumatoid arthritis complicated with atherosclerosis

“…Cytotoxic T-lymphocyte-associated protein 4 binds to this protein to negatively regulate T-cell activation and diminishes the immune response 49 C1QA complement C1q A chain C1QA encodes C1r and C1s associated proteins to yield the first component of the serum complement system. The deficiency is related to lupus erythematosus and glomerulonephritis 50 ITGB2 integrin subunit beta 2 This gene encodes an integrin beta chain. The encoded protein mainly affects immune response.…”

Identification of Transcriptional Pattern Related to Immune Cell Infiltration With Gene Co-Expression Network in Papillary Thyroid Cancer

“…The abnormal methylation of C1QA is also associated with the progression of thyroid cancer and is a potential biomarker (52). In osteosarcoma, the expression level of C1QA is positively correlated with patient survival time and levels of macrophage and CD8 cell in the tumor immune microenvironment (53). It has been reported that 3 human C1Q genes are closely bundled on chromosome 1 (C1QA-C1QC-C1QB) and their basal and IFNg-stimulated expression, largely restricted to macrophages and dendritic cells (54).…”