Clinical Significance Of Neutrophil Gelatinase-associated Lipocalin Exoression In Renal Cell Carcinoma

Objective:Neutrophil gelatinase-associated lipocalin(NGAL),also known as lipocalin-2,is a 25-kDa protein now considered the biochemical gold standard for early diagnosis of acute kidney injury.Recently,NGAL was suggested to play an important role in several human neoplasias.We sought to explore the feasibility and clinical significance of detection of urinary and plasmic NGAL in human renal tumors.We also aim to assess NGAL expression in different renal tumor types and analyze its association with clinicopathological parameters and prognosis.Methods:The level of NGAL in urine and plasma samples respectively from healthy control group and patients of renal tumor were determined by ELISA.Its relationship with clinicopathological features of renal tumors was further analyzed.Test the expression of NGAL in 17 renal cell carcinomas and normal kidney tissue by Western Blot.Test the expression of NGAL in 189 renal cell carcinomas by IHC,then the association of NGAL immunoexpression and clinicopathological characteristics was evaluated.Cox proportional hazard regression was performed to estimate the prognostic significance of potential confounders for predicting overall survival(OS)and disease-specific survival(DFS).Results:The value of urinary NGAL protein level in 86 cases of renal tumors was significantly higher than that in the healthy control group(P<0.01).Elevated level of urinary NGAL protein significantly correlated with tumor diameter,TNM stage,metastasis and histotype(p<0.01).NGAL expression in different histotypes of analyzed tumors was highly and significantly associated with papillary RCC(P<0.001).In papillary RCC,high NGAL expression was associated with high Fuhrman grade(P<0.001),tumor size>7 cm(P=0.007),increased tumor-node-metastasis stage(P<0.001)and lymph node metastasis(P=0.009).On univariable and multivariable Cox survival analyses of papillary RCC,after a median follow-up of 49.1 months(range 7 to 136 months),NGAL expression was associated with reduced OS(hazard ratio[HR]4.10,[95%confidence interval(95%CI)1.19-14.14],P=0.026)and DFS(HR 2.56[95%CI:1.01-6.48],P=0.047).Conclusion:Urinary NGAL level of renal tumor patients was significantly higher than that in the healthy control group.NGAL protein could served as the novel malignant biological phenotype marker for human renal cell carcinoma.NGAl highly expresses in papillary RCC and NGAL overexpression may be a prognostic predictor of reduced OS and DFS in papillary RCC.The association of NGAL overexpression and poor prognosis with papillary RCC might have potential diagnostic and therapeutic utility.