Abstract
BackgroundC5AR2 (GPR77, C5L2) is the second receptor for C5a that is a potent protein generated by complement activation. C5AR2 can mediate its own signaling events and exert significant immunomodulatory effects through those events. However, research of C5AR2 in cancer is limited, and its function remains unclear in breast cancer.MethodsThe expression of C5AR2 and its correlations with prognosis, immune infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI) in more than thirty types of cancers were described through GTEx, TCGA, PrognoScan, TIMER2.0, CCLE, HPA, and TISIDB database. C5AR2 showed strong relationships to those immune marker sets in breast cancer. Otherwise, CCK8 assay and Transwell assay were conducted to illustrate the role of C5AR2 in migration, invasion, and proliferation of breast cancer cells.ResultsGenerally, C5AR2 expression differed across most cancerous and noncancerous tissues, and high C5AR2 expression significantly related to poor prognosis in BRCA, GBM, KICH, LAML, LGG, LIHC, PAAD, and STAD. Moreover, C5AR2 expression levels were dramatically correlated with recognized immune infiltration, especially the polarization of macrophages in breast cancer. Gene set enrichment analysis confirmed that C5AR2 participates in regulating multiple signaling pathways involved in tumorigenesis as well as tumor immunity. C5AR2 overexpression facilitated the functions such as migration, invasion, and proliferation in breast cancer cells, which is consistent with bioinformatics analysis.ConclusionsC5AR2 is involved in immune infiltration and malignant characteristics of breast cancer, which may be a prospective biomarker for breast cancer.
Highlights
Breast cancer is the most frequently diagnosed cancer in women [1]
Generally, C5AR2 expression differed across most cancerous and noncancerous tissues, and high C5AR2 expression significantly related to poor prognosis in BRCA, GBM, KICH, LAML, LGG, LIHC, PAAD, and STAD
C5AR2 expression levels were dramatically correlated with recognized immune infiltration, especially the polarization of macrophages in breast cancer
Summary
Breast cancer is the most frequently diagnosed cancer in women [1]. The treatment usually includes surgery, radiation therapy, oral or intravenous anticancer drugs, hormone therapy and targeted biological antibodies [2]. In Clinical, it is usually classified into four subtypes: Luminal A, Luminal B, HER-2 overexpression, and triple negative breast cancer based on the expression of ER, PR, and HER-2 [3]. Due to high heterogeneity of breast cancer, to identify other biomarkers may benefit the diagnosis and therapeutics. There are two identified C5a receptors, C5aR1, known as CD88 likewise, and C5aR2, known as GPR77 or C5L2 likewise. The role of C5AR2 in properly controlling C5a is considerable; otherwise, excessive or unresolved C5a production can aggravate a plethora of acute and chronic diseases, such as ischemia-reperfusion injury, rheumatic arthritis, sepsis atherosclerosis, and cancer, even COVID-19 [10,11,12,13]. Research of C5AR2 in cancer is limited, and its function remains unclear in breast cancer
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
