Department of Surgery, University Hospital of Ioannina, Stavros Niarchos avenue, Ioannina 45500, Greece.
World J Surg Oncol. 2013 Aug 27;11:213. doi: 10.1186/1477-7819-11-213.
Debate about the potential effects that surgery might have on cancer cells dormancy and angiogenesis prompted us to investigate the impact of breast surgery on circulating angiogenesis modulating gene transcripts and proteins.
Blood samples from 10 female patients diagnosed with breast cancer and 6 with fibroadenoma were collected before surgery and post-operatively on days 3 and 7 (breast cancer patients only). A set of 84 angiogenesis-associated transcripts were assessed using quantitative PCR arrays, and circulating protein levels (vascular endothelial growth factor A (VEGFA), IL8 and fibroblast growth factor 2 (FGF2) were measured using ELISA in the same samples. The results were investigated against clinicopathological data and patient outcome.
Plasma levels of VEGFA and IL8 after surgery were significantly elevated in the breast cancer group compared to the control group (P = 0.038 and P = 0.021, respectively). In the cohort of breast cancer patients, VEGFA increased on day 3 (P = 0.038) and declined on day 7 (P= 0.017), while IL8 did not change on day 3 but showed a significant decline on day 7 (P = 0.02). FGF2 levels did not change significantly over time. Regarding gene transcripts, we detected upregulation of a significant number of angiogenesis-specific genes in patients with breast cancer versus controls: sphingosine kinase 1(SPHK1), epidermal growth factor (EGF), vascular endothelial growth factor C (VEGFC), neuropilin 1 (NRP1), fibroblast growth factor (FGF1), laminin alpha 5 (LAMA5), collagen type IV alpha 3 (COL4A3), IL8, ephrin B2 (EFNB2), ephrin A3 (EFNA3), tyrosine endothelial kinase (TEK), integrin beta 3 (ITGB3), AKT1, thrombospondin 1 (THBS1), chemokine (C-C motif) ligand 11 (CCL11) and TIMP metallopeptidase inhibitor 3 (TIMP3). Surgery induced an altered expression in several keygenes in breast cancer patients. We identified an upregulation of COL4A3 and downregulation of chemokine (C-X-C motif) ligand 9 (CXCL9), EGF, FGF1, Kinase insert domain receptor (KDR), Placental growth factor (PGF), TIMP3 and VEGFC.
Breast cancer patients have a different expression profile of circulating angiogenesis biomarkers compared to patients with fibroadenoma. Moreover, mastectomy promotes a transient increase of VEGFA and a shift in the expression patterns of a broad panel of angiogenesis-related circulating gene transcripts.
关于手术可能对癌细胞休眠和血管生成产生的潜在影响的争论促使我们研究乳房手术对循环血管生成调节基因转录本和蛋白的影响。
收集 10 名女性乳腺癌患者和 6 名纤维腺瘤患者手术前和术后第 3 天和第 7 天（仅乳腺癌患者）的血液样本。使用定量 PCR 阵列评估了一组 84 个与血管生成相关的转录本，并用 ELISA 测量了相同样本中的循环蛋白水平（血管内皮生长因子 A(VEGFA)、白细胞介素 8(IL8)和成纤维细胞生长因子 2(FGF2)。结果针对临床病理数据和患者结局进行了调查。
与对照组相比，乳腺癌组手术后血浆 VEGFA 和 IL8 水平显着升高（P=0.038 和 P=0.021）。在乳腺癌患者队列中，VEGFA 在第 3 天增加（P=0.038），第 7 天下降（P=0.017），而 IL8 在第 3 天没有变化，但第 7 天显着下降（P=0.02）。FGF2 水平随时间无明显变化。关于基因转录本，我们检测到与对照组相比，乳腺癌患者中大量血管生成特异性基因上调：鞘氨醇激酶 1(SPHK1)、表皮生长因子(EGF)、血管内皮生长因子 C(VEGFC)、神经纤毛蛋白 1(NRP1)、成纤维细胞生长因子 1(FGF1)、层粘连蛋白α 5(LAMA5)、IV 型胶原α 3(COL4A3)、白细胞介素 8(IL8)、ephrin B2(EFNB2)、ephrin A3(EFNA3)、酪氨酸内皮激酶(TEK)、整合素β 3(ITGB3)、AKT1、血小板反应蛋白 1(THBS1)、趋化因子(C-C 基序)配体 11(CCL11)和金属蛋白酶组织抑制剂 3(TIMP3)。手术诱导乳腺癌患者中几个关键基因的表达发生改变。我们发现 COL4A3 上调和趋化因子(C-X-C 基序)配体 9(CXCL9)、EGF、FGF1、激酶插入结构域受体(KDR)、胎盘生长因子(PGF)、TIMP3 和 VEGFC 下调。
与纤维腺瘤患者相比，乳腺癌患者循环血管生成生物标志物的表达谱不同。此外，乳房切除术会导致 VEGFA 短暂增加，并导致广泛的与血管生成相关的循环基因转录本表达模式发生变化。
