Pathological significance of C3aR signaling in the tumor cells of clear cell renal cell carcinoma: a clinical observation

Abstract

Background Increasing evidences suggest that anaphylotoxin-induced signaling is involved in tumor pathogenesis, but the exact role of C3a/C3aR signaling in clear cell renal cell carcinoma (ccRCC) still remains to be investigated. The aim of the study was to investigate the pathological significance of C3a/C3aR signaling in ccRCC. MethodsThe expression of C3aR and C3 mRNA in the tumor tissues of ccRCC patients were analyzed by using the data from TCGA database. The expression of C3aR and C3c protein in the tumor tissues of another 129 ccRCC patients were examined by immunohistochemistry. ResultsCompared with the normal controls, both C3aR and C3 mRNA increased in the tumor tissues.Patients with higher C3 mRNA had shorter survival time. Immunostaining for C3aR and C3c also increased in the tumor tissues when compared with the adjacent normal renal tissues. Higher level of C3aR in the tumor cells and C3c in the tumor tissues were found to be associated with indices reflecting poor prognosis including higher tumor grade, the presence of necrosis in tumor tissues and shorter survival time. Besides, the level of C3aR in the tumor cells and C3c in the tumor tissues were found to correlate with the level of Vimentin, E-Cadherin and the ratio of Ki-67 positive tumor cells. ConclusionsThese results support the idea that C3aR signaling is over-activated in the tumor cells and may contribute to the progression of ccRCC. Inducing EMT and promoting the proliferation of tumor cells might be among the mechanisms underlying the role of C3aR signaling in ccRCC. BackgroundRenal cell carcinoma (RCC) is one of the most common malignant tumors in the urinary system. It is among the top ten most commonly diagnosed cancers worldwide [1]. Clear cell renal cell carcinoma (ccRCC) is the major histological subtype of RCC, comprising more than 70% of all RCC cases [2]. ccRCC is commonly resistant to conventional chemotherapy and radiotherapy. Early surgical resection is the preferred therapy. However, up to 40% of ccRCC patients with localized disease will eventually suffer a relapse or develop metastatic disease even after nephrectomy [3][4]. In the last two decades, some adjuvant therapies including immunotherapy and target therapy have been introduced to treat patients with metastatic ccRCC. However, these therapies either have limited effect and severe side