title: Expression of IL-4 and IL-13 predicts recurrence and survival in localized clear-cell renal cell carcinoma.
abstract: Interleukin-4 (IL-4) and IL-13 are anti-inflammatory and immunoregulatory cytokines that can influence cancer-directed immunosurveillance. However, they are not evaluated as biomarkers for ccRCC outcomes. The aim of this study was to investigate the prognostic value of tumor-derived IL-4 and IL-13 in patients with localized ccRCC after surgery. Our study comprised 194 consecutive patients with localized ccRCC undergoing nephrectomy in a single center. Clinical characteristics, recurrence-free survival (RFS) and overall survival (OS) were recorded. We assessed IL-4 and IL-13 expression as continuous variables and dichotomized as low versus high by immunohistochemistry. For associations with RFS and OS, we used the Kaplan-Meier method and Cox regression models. Concordance index was calculated for predictive accuracy. We found that high expression levels of IL-4 and IL-13 were associated with increased recurrence (P < 0.001 and P = 0.006, respectively) and reduced survival (P = 0.001 and P = 0.016, respectively). Furthermore, multivariate analyses confirmed that combination of IL-4 and IL-13 expression (IL-4/IL-13 signature) was an independent prognostic factor for RFS and OS (P = 0.009 and P = 0.016, respectively). When applied to UISS score, IL-4/IL-13 signature improved the predictive accuracy. Notably, this improvement in prediction was mainly observed in patients with low-risk disease. To conclude, IL-4/IL-13 signature is an independent predictor of outcomes in patients with localized ccRCC, and the prognostic value is more prominent among patients with low-risk disease. Evaluation of IL-4 and IL-13 expression provides the opportunity to optimize postsurgical management and develop novel targeted therapies for ccRCC patients.
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: An
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pathology, Children's Hospital, Fudan University Shanghai, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Urology, Zhongshan Hospital, Fudan University Shanghai, China.
authors.forename: Zongming
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University Shanghai, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018793:Interleukin-13 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D059467:Transcriptome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C578095:IL13 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D015847:Interleukin-4
keywords: Renal cell carcinoma; biomarker; interleukin-13; interleukin-4; prognosis