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

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...

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Main Authors: Long-hao Chen, Jin-Fu Liu, Yan- Lu, Xin-yu He, Chi- Zhang, Hong-hai Zhou
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.642144/full
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author Long-hao Chen
Jin-Fu Liu
Yan- Lu
Xin-yu He
Chi- Zhang
Hong-hai Zhou
author_facet Long-hao Chen
Jin-Fu Liu
Yan- Lu
Xin-yu He
Chi- Zhang
Hong-hai Zhou
author_sort Long-hao Chen
collection DOAJ
description 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.
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spelling doaj.art-822e06b8780c4af5999d157ce588cd032022-12-21T22:46:25ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.642144642144Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in OsteosarcomaLong-hao Chen0Jin-Fu Liu1Yan- Lu2Xin-yu He3Chi- Zhang4Hong-hai Zhou5Faculty of Orthopedics and Traumatology, Guangxi University of Chinese Medicine, Nanning, ChinaGraduate School, Guangxi University of Chinese Medicine, Nanning, ChinaFaculty of Orthopedics and Traumatology, Guangxi University of Chinese Medicine, Nanning, ChinaFaculty of Orthopedics and Traumatology, Guangxi University of Chinese Medicine, Nanning, ChinaGraduate School, Guangxi University of Chinese Medicine, Nanning, ChinaFaculty of Orthopedics and Traumatology, Guangxi University of Chinese Medicine, Nanning, ChinaThe 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.https://www.frontiersin.org/articles/10.3389/fonc.2021.642144/fullC1q (A/B/C)tumor microenvironmentosteosarcomatumor-infiltrating immune cellsCIBERSORTESTIMATE
spellingShingle Long-hao Chen
Jin-Fu Liu
Yan- Lu
Xin-yu He
Chi- Zhang
Hong-hai Zhou
Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma
Frontiers in Oncology
C1q (A/B/C)
tumor microenvironment
osteosarcoma
tumor-infiltrating immune cells
CIBERSORT
ESTIMATE
title Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma
title_full Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma
title_fullStr Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma
title_full_unstemmed Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma
title_short Complement C1q (C1qA, C1qB, and C1qC) May Be a Potential Prognostic Factor and an Index of Tumor Microenvironment Remodeling in Osteosarcoma
title_sort complement c1q c1qa c1qb and c1qc may be a potential prognostic factor and an index of tumor microenvironment remodeling in osteosarcoma
topic C1q (A/B/C)
tumor microenvironment
osteosarcoma
tumor-infiltrating immune cells
CIBERSORT
ESTIMATE
url https://www.frontiersin.org/articles/10.3389/fonc.2021.642144/full
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