Clinicopathological features and prognostic significance of C5aR in human solid tumors: a Meta-analysis

Abstract

Background C5aR has been extensively studied in recent years as an essential component of the complement system. However, the role of C5aR in tumors has not been sufficiently investigated and summarized. The aim of this meta-analysis was to investigate the prognostic value of C5aR in solid tumors as well as the correlation between C5aR and clinicopathological features. Methods Relevant study collection was performed in PubMed, Embase, Web of Science, BIOSIS Previews, Cochrane Library until July 10, 2021. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were performed to assess the robustness of this study, while publication bias was tested by Begg’s and Egger’s tests. Results A total of 11 studies involving 1577 patients were included in the study. Our results suggest that the high-level C5aR expression in tumor tissue predicted unsatisfactory overall survival (OS) (HR = 1.92, 95% CI:1.47–2.50, P < 0.001) and recurrence-free survival (RFS) (HR = 2.19, 95% CI:1.47–3.27, P < 0.001). Besides, a higher level of C5aR expression was associated with larger tumor size (OR = 1.58, 95% CI: 1.18–2.10, P = 0.002) and the occurrence of metastases in lymph nodes (OR = 1.99, 95% CI: 1.46–2.72, P<0.001), whereas it was independent of tumor stage, vascular invasion and tumor differentiation. Conclusion In conclusion, C5aR may be a potential biomarker for evaluating tumor prognosis and treatment.

Atomic force microscopy applied to interrogate nanoscale cellular chemistry and supramolecular bond dynamics for biomedical applications

“…5 In Dumitru et al (2020), 70 we explored the behaviour of human G protein-coupled C5a Receptor (C5aR), using affinity imaging to detect orientation of the protein in lipid membranes and identifying, for the first time, a cooperative binding mechanism likely tied to its function. Given the receptor's role in chemotaxis, 71 inflammatory responses, 72 cell activation, 73 and links to inflammatory pathologies, 74,75 Alzheimer's disease, 76 and cancers, 77 understanding the molecular binding behaviours and functioning of C5aR is important for the development and application of therapeutics. Using a combination of FD-AFM and molecular simulations, we identified for the first time an allosteric two-step binding process occurring at separate positions within the structure.…”