BackgroundThe purpose of this study was to validate B7-H3 as a new cancer-specific endothelial marker in clear cell renal cell carcinoma.MethodsB7-H3 expression patterns were compared between cancer and paired adjacent normal renal parenchyma by immunohistochemistry in paraffin-embedded specimens from 200 consecutive patients with clear cell renal cell carcinoma from January to December 2010. Four corpus luteum specimens were used as physiologic angiogenesis controls. B7-H3 messenger (m)RNA levels representing circulating endothelial cells were analyzed in 24 peripheral blood samples using real-time polymerase chain reaction. Collection and processing of tissue and peripheral blood samples was performed in compliance with the Declaration of Helsinki.ResultsCancer cell-specific expression of B7-H3 was detected in 19% of clear cell renal cell carcinoma specimens, and tumor vasculature B7-H3 expression was confirmed in 98% (196) of cases. A diffuse pattern of vascular B7-H3 expression was associated with multiple adverse clinical and pathologic features (P<0.001). B7-H3 expression was not detected in paired adjacent normal renal parenchyma or vessels, or in luteal blood vessels. The B7-H3 mRNA level of circulating endothelial cells in peripheral blood was significantly higher in metastatic clear cell renal cell carcinoma (P<0.001).ConclusionThis pilot study indicates that B7-H3 is a cancer-specific endothelial marker of potential importance for the development of tumor-specific, vascular-targeted therapies, and is a prognostic marker in clear cell renal cell carcinoma.

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Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.