Prognostic and immune-related value of complement C1Q (C1QA, C1QB, and C1QC) in skin cutaneous melanoma

Abstract

Background: Skin cutaneous melanoma (SKCM) is a common malignancy that is associated with increased morbidity and mortality. Complement C1Q is composed of C1QA, C1QB, and C1QC and is involved in the occurrence and development of many malignant tumours. However, the effect of C1QA, C1QB, and C1QC expression on tumour immunity and prognosis of cutaneous melanoma remains unclear.Methods: First, we analysed C1QA, C1QB, and C1QC expression levels and prognostic values using Gene Expression Profiling Interactive Analysis (GEPIA) and Tumour Immune Estimation Resource (TIMER) analysis, and further validation was performed using RT-qPCR, The Human Protein Atlas, The Cancer Genome Atlas (TCGA) dataset, and Gene Expression Omnibus dataset. We then performed univariate/multivariate Cox proportional hazard model, clinicopathological correlation, and receiver operating characteristic curve analysis using TCGA dataset and established a nomogram model. Differentially expressed genes associated with C1QA, C1QB, and C1QC in SKCM were identified and analysed using LinkedOmics, TIMER, the Search Tool for the Retrieval of Interacting Genes database, and Metascape and Cytoscape software platforms. We used TIMER, GEPIA, and single-sample gene set enrichment analysis (ssGSEA) to analyse the relationship between the three genes and the level of immune cell infiltration, biomarkers, and checkpoint expression in SKCM. Finally, GSEA was utilized to study the functional pathways of C1QA, C1QB, and C1QC enrichment in SKCM.Results: The overexpression of C1QA, C1QB, and C1QC provided significant value in the diagnosis of SKCM and has been associated with better overall survival (OS). Multivariate Cox regression analysis indicated that C1QA, C1QB, and C1QC are independent prognostic biomarkers for patients with SKCM. Immune cell infiltration, biomarkers, and checkpoints were positively correlated with the expression of C1QA, C1QB, and C1QC. Furthermore, the results of functional and pathway enrichment analysis showed that immune-related and apoptotic pathways were significantly enriched in the high-expression group of C1QA, C1QB, and C1QC.Conclusion: We found that C1QA, C1QB, and C1QC can be used as biomarkers for the diagnosis and prognosis of SKCM patients. The upregulated expression levels of these three complement components benefit patients from OS and may increase the effect of immunotherapy. This result may be due to the dual effects of anti-tumour immunity and apoptosis.

Impact of Complement C1qA and Complement C1qB on the Prognosis of Osteosarcoma

“…The over-expression of C1QA and C1QB are protective factors to significantly prolong the survival time and the risk factors<1. In a study about skin cutaneous melanoma, the researcher found that over-expression levels of C1QA, C1QB and C1QC are protective factors which improve survival time at different stages [21] . The results obtained are consistent with our results.…”

Tumor Purity-Related Genes for Predicting the Prognosis and Drug Sensitivity of DLBCL Patients

“…Moreover, C1QB expression shows a positive correlation with predictive biomarkers for immunotherapy, such as PD-L1 expression and CD8+ T cell infiltration[24]. Furthermore, in malignant melanoma, C1QB promotes proliferation, migration and invasion, while inhibiting cell apoptosis[26], and the high-expression group exhibits significant enrichment of genes related to immune and apoptosis[21]. In our study, we found that high expression of C1QB in DLBCL was associated with a worse prognosis and positively correlated with CD8+ T cells infiltration.…”

Identification of the pyroptosis-related gene signature and risk score model for esophageal squamous cell carcinoma

“…HLA class I antigen deletion caused by B2M mutation mostly occurs under the activated PDCD1 (PD-1)-positive T cell infiltration condition [ 26 ]. C1QB is the diagnostic and prognostic biomarker for skin cutaneous melanoma patients [ 27 ], IRF4 could promote melanoma cell growth via upregulating C1QB [ 28 ]. The combination of C2 and additional therapeutic mAbs, such as type II anti-CD20/CD22/CD38 samples, can overcome complement attack resistance in tumor cells [ 29 ].…”