基质细胞中血管内皮生长因子 165b 的表达与结直肠癌。
Vascular endothelial growth factor 165b expression in stromal cells and colorectal cancer.
机构信息
The First Department of Surgery, Sapporo Medical University, South 1, West 16, Chuo-ku, Sapporo 060-8543, Japan.
出版信息
World J Gastroenterol. 2011 Nov 28;17(44):4867-74. doi: 10.3748/wjg.v17.i44.4867.
AIM
To characterize the implications of vascular endothelial growth factor (VEGF)-A in stromal cells and colorectal cancer and the expression of VEGF-A splice variants.
METHODS
VEGF-A expression in tumor and stromal cells from 165 consecutive patients with colorectal cancer was examined by immunohistochemistry. The association between VEGF-A expression status and clinicopathological factors was investigated. Twenty fresh-frozen samples were obtained for laser capture microdissection to analyze the splice variants of VEGF-A.
RESULTS
VEGF-A was expressed in 53.9% and 42.4% of tumor and stromal cells, respectively. VEGF-A expression in tumor cells (t-VEGF-A) was associated with advanced clinical stage (stage 0, 1/9; stage 1, 2/16; stage 2, 32/55; stage 3, 38/66; stage 4, 16/19, P < 0.0001). VEGF-A expression in stromal cells (s-VEGF-A) increased in the earlier clinical stage (stage 0, 7/9; stage 1, 6/16; stage 2, 33/55; stage 3, 22/66; stage 4, 5/19; P = 0.004). Multivariate analyses for risk factors of recurrence showed that only s-VEGF-A expression was an independent risk factor for recurrence (relative risk 0.309, 95% confidence interval 0.141-0.676, P = 0.0033). The five-year disease-free survival (DFS) rates of t-VEGF-A-positive and -negative cases were 51.4% and 62.9%, respectively. There was no significant difference in t-VEGF-A expression status. The five-year DFS rates of s-VEGF-A-positive and -negative cases were 73.8% and 39.9%, respectively. s-VEGF-A-positive cases had significantly better survival than s-VEGF-A-negative cases (P = 0.0005). Splice variant analysis revealed that t-VEGF-A was mainly composed of VEGF165 and that s-VEGF-A included both VEGF165 and VEGF165b. In cases with no venous invasion (v0), the level of VEGF165b mRNA was significantly higher (v0 204.5 ± 122.7, v1 32.5 ± 36.7, v2 2.1 ± 1.7, P = 0.03). The microvessel density tended to be lower in cases with higher VEGF165b mRNA levels.
CONCLUSION
s-VEGF-A appears be a good prognostic factor for colorectal cancer and includes VEGF165 and VEGF165b.
目的
描述血管内皮生长因子 A（VEGF-A）在基质细胞和结直肠癌中的意义以及 VEGF-A 剪接变体的表达。
方法
采用免疫组织化学法检测 165 例连续结直肠癌患者肿瘤和基质细胞中的 VEGF-A 表达。研究 VEGF-A 表达状态与临床病理因素之间的关系。对 20 例新鲜冷冻样本进行激光捕获显微切割，以分析 VEGF-A 的剪接变体。
结果
肿瘤细胞（t-VEGF-A）和基质细胞（s-VEGF-A）中分别有 53.9%和 42.4%表达 VEGF-A。t-VEGF-A 的表达与较晚的临床分期（0 期，1/9；1 期，2/16；2 期，32/55；3 期，38/66；4 期，16/19，P<0.0001）相关。s-VEGF-A 的表达在较早的临床分期中增加（0 期，7/9；1 期，6/16；2 期，33/55；3 期，22/66；4 期，5/19；P=0.004）。复发风险因素的多变量分析表明，仅 s-VEGF-A 的表达是复发的独立危险因素（相对风险 0.309，95%置信区间 0.141-0.676，P=0.0033）。t-VEGF-A 阳性和阴性病例的 5 年无病生存率（DFS）分别为 51.4%和 62.9%。t-VEGF-A 表达状态无显著差异。s-VEGF-A 阳性和阴性病例的 5 年 DFS 率分别为 73.8%和 39.9%。s-VEGF-A 阳性病例的生存明显优于 s-VEGF-A 阴性病例（P=0.0005）。剪接变体分析显示，t-VEGF-A 主要由 VEGF165 组成，s-VEGF-A 则包括 VEGF165 和 VEGF165b。在无静脉侵犯（v0）的病例中，VEGF165b mRNA 的水平明显更高（v0 204.5±122.7，v1 32.5±36.7，v2 2.1±1.7，P=0.03）。VEGF165b mRNA 水平较高的病例中微血管密度倾向于较低。
结论
s-VEGF-A 似乎是结直肠癌的一个良好预后因素，包括 VEGF165 和 VEGF165b。
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