Enrichment of C5a-C5aR axis predicts poor postoperative prognosis of patients with clear cell renal cell carcinoma

Oncotarget. 2016 Dec 6;7(49):80925-80934. doi: 10.18632/oncotarget.13108.

Abstract

Anaphylatoxin C5a and its receptor C5aR on cancer cells constitute a vital axis to cancer progression. In this study, we measured C5aR level by immunohistochemistry in the same cohort of our previous C5a research, and C5a-C5aR axis status was determined by synthesizing C5a and C5aR data. C5aR was an adverse independent prognostic factor for ccRCC patients. Kaplan-Meier analyses revealed the unique position of both C5a and C5aR high population in postoperative survival, based on which patients were then shunted into C5a-C5aR enriched and non-enriched groups. Obviously, C5a-C5aR enriched patients significantly had a poorer overall survival (OS) and recurrence free survival (RFS) compared with non-enriched ones, and the independence of C5a-C5aR axis was verified by multivariable analyses (HR 2.118, P = 0.001 for OS, HR 1.715, P = 0.035 for RFS). Established nomograms based on our findings reflected much better predicting accuracy in contrast with most common used TNM and Fuhrman systems. Meanwhile, consistent with HR, C5a-C5aR axis in this study held its advantages over C5a and C5aR for OS prediction by c-index analyses, rather than RFS prediction.

Keywords: C5a-C5aR axis; C5aR; ccRCC; nomogram; prognosis.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery*
  • Chi-Square Distribution
  • Complement C5a / analysis*
  • Decision Support Techniques
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Kidney Neoplasms / chemistry
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Nephrectomy* / adverse effects
  • Nephrectomy* / mortality
  • Nomograms
  • Predictive Value of Tests
  • Proportional Hazards Models
  • ROC Curve
  • Receptor, Anaphylatoxin C5a / analysis*
  • Retrospective Studies
  • Risk Factors
  • Signal Transduction
  • Time Factors
  • Tissue Array Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • C5AR1 protein, human
  • Receptor, Anaphylatoxin C5a
  • Complement C5a