Twist 调节淋巴管生成并与声门上型癌的淋巴结转移相关。

Twist modulates lymphangiogenesis and correlates with lymph node metastasis in supraglottic carcinoma.

机构信息

Institute of Eye and Ear Nose Throat Branch, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

出版信息

Chin Med J (Engl). 2011 May;124(10):1483-7.

PMID:21740802

Abstract

BACKGROUND

Twist is a highly conserved epithelial-mesenchymal transcription factor that has been reported to be a key factor in tumor malignancy, including lymph node metastasis. It represents the major step of dissemination and serves as a chief prognostic indicator of disease progression. However, the mechanism by which Twist regulates lymph node metastasis remains incompletely understood. Studies on the mechanism of metastasis are thus required for determining appropriate therapeutic strategies.

METHODS

Immunohistochemistry for lymphatic vessel endothelial receptor 1 (LYVE-1), Ki-67, Twist, vascular endothelial growth factor C (VEGF-C), and vascular endothelial growth factor receptor 3 (VEGFR-3) was performed to detect lymphatic vessel density (LVD), cell proliferation levels and the expressions of Twist, VEGF-C, and VEGFR-3 were determined from 66 primary supraglottic carcinoma tissue samples from 36 patients with lymph node metastasis (pathological N+, pN+) and 30 patients without metastasis (pathological N0, pN0). Western blotting analysis of the proteins in pN+ and pN0 primary tumors was used to characterize the expressions of Twist, VEGF-C, and VEGFR-3 further.

RESULTS

The LVD was 22.4 ± 10.3 in pN+ patients and 6.8 ± 4.1 in pN0 ones. For Ki-67, the number of proliferous cells in pN+ patients was greater than that in pN0 ones. Both, however, were associated with their clinical nodal stages. In pN+ patients, Twist, VEGF-C, and VEGFR-3 expressions were 86.11% (31/36), 80.56% (29/36), and 58.33% (21/36), respectively. These values were higher than those found for pN0 patients (i.e., 13/30, 11/30, and 7/30, respectively) (P < 0.05). Among the samples with Twist expression, 88.64% were VEGF-C-positive and 59.09% were VEGFR-3-positive. The pN0 counterparts were 4.55% and 9.09%, respectively (P < 0.05). The expressions of Twist, VEGF-C, and VEGFR-3 in pN+ patients obtained through Western blotting analysis were significantly higher than those in pN0 patients, and the levels of VEGF-C and VEGFR-3 were positively correlated with that of Twist.

CONCLUSIONS

Twist expression correlates with lymph node metastasis. The mechanism involved in such a correlation may be related to lymphangiogenesis.

摘要

背景

Twist 是一种高度保守的上皮-间充质转录因子，已被报道是肿瘤恶性的关键因素，包括淋巴结转移。它代表了播散的主要步骤，并且是疾病进展的主要预后指标。然而，Twist 调节淋巴结转移的机制仍不完全清楚。因此，需要对转移机制进行研究，以确定适当的治疗策略。

方法

对 36 例有淋巴结转移（病理 N+，pN+）和 30 例无转移（病理 N0，pN0）的 36 例原发性声门上型癌组织样本进行淋巴管内皮受体 1（LYVE-1）、Ki-67、Twist、血管内皮生长因子 C（VEGF-C）和血管内皮生长因子受体 3（VEGFR-3）的免疫组化检测，以检测淋巴管密度（LVD），并确定细胞增殖水平以及 Twist、VEGF-C 和 VEGFR-3 的表达水平。Western 印迹分析 pN+和 pN0 原发肿瘤中的蛋白质，进一步分析 Twist、VEGF-C 和 VEGFR-3 的表达。

结果

pN+患者的 LVD 为 22.4±10.3，pN0 患者为 6.8±4.1。Ki-67 增殖细胞数在 pN+患者中大于 pN0 患者。然而，这两者都与他们的临床淋巴结分期有关。在 pN+患者中，Twist、VEGF-C 和 VEGFR-3 的表达分别为 86.11%（31/36）、80.56%（29/36）和 58.33%（21/36），这些值高于 pN0 患者（即 13/30、11/30 和 7/30）（P<0.05）。在有 Twist 表达的样本中，88.64%为 VEGF-C 阳性，59.09%为 VEGFR-3 阳性。pN0 患者的相应比例分别为 4.55%和 9.09%（P<0.05）。通过 Western 印迹分析，pN+患者的 Twist、VEGF-C 和 VEGFR-3 表达明显高于 pN0 患者，且 VEGF-C 和 VEGFR-3 的水平与 Twist 呈正相关。