Abstract
Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions. We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC). We used real-time quantitative PCR to examine the VCAM1 expression levels of a total of 485 sporadic renal tumors, including 429 clear cell, 21 papillary, 17 chromophobe, 11 oncocytomas, and 7 collecting duct carcinomas. We retrospectively examined the relationship of this expression to various clinicopathologic variables and the von Hippel-Lindau alteration status. We evaluated its significance with respect to patient survival rates using the Cox regression model combined with the split-sample method. Compared with normal kidney samples (n = 43), VCAM1 was significantly up-regulated in clear cell RCC and papillary RCC, whereas it was down-regulated in chromophobe RCC and oncocytoma. In clear cell RCC, VCAM1 expression levels were apparently high in patients asymptomatic at presentation and in patients with small tumor size, low-stage, low-grade, microvascular invasion-negative, and von Hippel-Lindau alteration-positive tumors. Univariate analyses showed that VCAM1 high expression is strongly associated with better outcomes in clear cell and papillary RCCs. Further, Cox multivariate analysis models combined with the split-sample method revealed that this association is significant only in cancer-free survival for patients with clear cell RCC after curative surgical resection. VCAM1 expression levels were found to be histologically subtype specific in renal tumors. Determination of the VCAM1 expression level as a biomarker can provide useful prognostic information for patients with clear cell RCC.
Highlights
Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions.We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC)
We initially evaluated the reproducibility of the real-time quantitative PCR (RQ-PCR) assay
When comparing the VCAM1 signal levels detected by the GeneChip and RQ-PCR, we found that the reproducibility between these two procedures was quite high (Spearman rank correlation coefficient, q = 0.895 and 0.877, respectively)
Summary
Vascular cell adhesion molecule 1 (VCAM1) is a cell surface glycoprotein implicated in various pathophysiologic conditions.We measured VCAM1 expression levels in tumor tissues and evaluated its significance and prognostic use in renal cell carcinoma (RCC). With respect to microarray studies for RCC, several groups have reported the identification of sets of genes that are exclusively expressed in renal tumor subtypes or that may predict clinical outcomes based solely on gene expression levels (12 – 17). Among these works, Vasselli et al [13] have recently found that expression levels of vascular cell adhesion molecule 1 (VCAM1) show the highest statistically predictive value for the survival of patients with stage IV metastatic RCC. To further elucidate the significance of VCAM1 as a biomolecular marker for RCC, we measured www.aacrjournals.org
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