Department of Medicine, Centre for Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
Eur J Clin Invest. 2013 Aug;43(8):801-8. doi: 10.1111/eci.12108. Epub 2013 May 18.
Circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), Willebrand factor (vWf), soluble E-selectin, vascular endothelial growth factor (VEGF) and angiogenin are of interest in cancer vascular biology. However, few studies have looked at more than one in combination. We set out to determine which would be best in predicting the Dukes' and American Joint Committee on Cancer (AJCC) scores in colorectal cancer patients.
We recruited 154 patients with colorectal cancer, 29 healthy controls and 26 patients with benign bowel disease. CD34(+) /CD45(-) /CD146(+) CECs and CD34(+) /CD45(-) /CD309KDR EPCs were measured by flow cytometry, plasma markers by ELISA.
All research indices were raised in colorectal cancer (P < 0·05) compared to control groups. Although CECs (P < 0·05), EPCs (P < 0·01) and angiogenin (P < 0·01) increased stepwise across the four Dukes' stages and four AJCC stages, only angiogenin remained significant in multiple regression analysis (P = 0·003 for Dukes, P = 0·01 for AJCC). Angiogenin levels were higher in Dukes' stages C and D compared to stage A, and AJCC stages 4-6 and 7-10 compared to stage 1 (all P < 0·05). Adding a second research marker to angiogenin did not markedly improve this relationship.
Although we found disturbances in endotheliod cells and plasma markers of the endothelium and growth factors, only angiogenin levels were independently associated with progression of the Dukes' stage and AJCC stage, with the association with Duke's stage being stronger. We suggest that angiogenin is a potential biomarker in risk stratification for colorectal cancer, and may aid clinical decision making.
循环内皮细胞(CEC)、内皮祖细胞(EPC)、血管性血友病因子(vWf)、可溶性 E-选择素、血管内皮生长因子(VEGF)和血管生成素在癌症血管生物学中受到关注。然而,很少有研究同时观察超过一种。我们旨在确定哪些指标最能预测结直肠癌患者的 Dukes 分期和美国癌症联合委员会(AJCC)分期。
我们招募了 154 名结直肠癌患者、29 名健康对照者和 26 名良性肠道疾病患者。通过流式细胞术测量 CD34(+) / CD45(-) / CD146(+) CEC 和 CD34(+) / CD45(-) / CD309KDR EPC,通过 ELISA 测量血浆标志物。
与对照组相比,所有研究指标在结直肠癌患者中均升高(P < 0·05)。虽然 CEC(P < 0·05)、EPC(P < 0·01)和血管生成素(P < 0·01)在 Dukes 分期的四个阶段和 AJCC 分期的四个阶段中呈逐步升高,但只有血管生成素在多元回归分析中仍然显著(P = 0·003 用于 Dukes,P = 0·01 用于 AJCC)。与 Dukes 分期 A 相比,分期 C 和 D 的血管生成素水平更高,与 AJCC 分期 4-6 和 7-10 相比,分期 1 的水平更高(均 P < 0·05)。将第二个研究标志物添加到血管生成素中并没有显著改善这种关系。
尽管我们发现内皮细胞和内皮和生长因子的血浆标志物存在紊乱,但只有血管生成素水平与 Dukes 分期和 AJCC 分期的进展独立相关,与 Dukes 分期的相关性更强。我们认为血管生成素是结直肠癌风险分层的潜在生物标志物,可能有助于临床决策。