补体在肝细胞癌临床病程中的作用。
The role of complement in the clinical course of hepatocellular carcinoma.
机构信息
Center of Hepatobiliary Pancreatic Disease, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China.
Department of Anesthesiology, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Immun Inflamm Dis. 2022 Mar;10(3):e569. doi: 10.1002/iid3.569. Epub 2021 Nov 23.
BACKGROUND
The complement system, an innate immune system, may either play an antitumor role, or promote tumorigenesis and cancer progression in different kinds of cancer. The function of complement in hepatocellular carcinoma (HCC) is unclear.
METHODS
The gene expressions of the complement system were based on data obtained from TCGA and GEO. We explored gene expressions, mutation, enrichment analysis, clinicopathology, patients' outcome, and immune infiltration via Gepia2, cBioPortal, Metascape, UALCAN, Kaplan-Meier Plotter, and TIMER 2.
RESULTS
Five complement genes, including C1R, C6, C7, CFP, and CFHR3, were not only found to be significantly downregulated in HCC samples compared with normal liver samples, but also found to be significantly associated with overall survival, disease-free survival, and progress-free survival in HCC patients. In addition, lower mRNA expression of C1R, C6, C7, and CFHR3 were found correlated with advanced cancer stages and higher tumor grades in HCC patients. Also, the expression levels of CFP were correlated with many sets of immune markers of tumor immune cells, such as those of CD8+ T cells, CD4+ T cells, B cells, M2 macrophages, neutrophils, DCs, Th1 cells, Th2 cells, and T cell exhaustion in HCC. Based on that, we developed a prognostic model for HCC patients-Riskscore = (-0.0053)*C6+(-0.0498)*C7+(-0.1045)*CFHR3.
CONCLUSION
C1R, C6, C7, CFP, and CFHR3 could be prognostic biomarkers for patients with HCC.
背景
补体系统作为先天免疫系统，在不同类型的癌症中可能发挥抗肿瘤作用，也可能促进肿瘤发生和癌症进展。补体在肝细胞癌（HCC）中的作用尚不清楚。
方法
基于 TCGA 和 GEO 获得的补体系统基因表达数据，我们通过 Gepia2、cBioPortal、Metascape、UALCAN、Kaplan-Meier Plotter 和 TIMER 2 进行基因表达、突变、富集分析、临床病理、患者预后和免疫浸润分析。
结果
五种补体基因（C1R、C6、C7、CFP 和 CFHR3）不仅在 HCC 样本中与正常肝样本相比表达显著下调，而且与 HCC 患者的总生存期、无病生存期和无进展生存期显著相关。此外，C1R、C6、C7 和 CFHR3 的低 mRNA 表达与 HCC 患者的晚期癌症分期和较高的肿瘤分级相关。此外，CFP 的表达水平与肿瘤免疫细胞的许多免疫标志物相关，如 HCC 中的 CD8+T 细胞、CD4+T 细胞、B 细胞、M2 巨噬细胞、中性粒细胞、DC、Th1 细胞、Th2 细胞和 T 细胞衰竭。基于此，我们为 HCC 患者开发了一个预后模型-Riskscore=(-0.0053)*C6+(-0.0498)*C7+(-0.1045)*CFHR3。
结论
C1R、C6、C7、CFP 和 CFHR3 可能是 HCC 患者的预后生物标志物。
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