Abstract

We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC. A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases. ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration-positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak. The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.

Highlights

  • We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC)

  • These findings suggest that disruption of the von HippelLindau disease (VHL) tumor suppressor/hypoxia-inducible factor (HIF) pathway is likely involved in the up-regulation of ADFP in clear cell RCC [11]

  • We examined a total of 432 primary sporadic clear cell RCCs as well as 49 corresponding normal kidney samples for ADFP expression levels using realtime quantitative PCR

Read more

Summary

Introduction

We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). The clinicopathologic and prognostic data were collected, as well as the von HippelLindau disease (VHL) gene alteration status in selected cases. Conclusions: The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC. It has been shown that HIF-a is the critical target for ubiquitin-dependent proteasome degradation by the VHLElonginBC-Cul2/Rbx ubiquitin ligase complex in clear cell RCC cells [4, 9, 10] These findings suggest that disruption of the VHL tumor suppressor/HIF pathway is likely involved in the up-regulation of ADFP in clear cell RCC [11]. Our preliminary data suggested that patients with tumors that showed a high level of ADFP expression had better survival rates than patients with tumors having a low level of ADFP expression [11]

Methods
Results
Conclusion
Full Text
Published version (Free)

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 call