淋巴管平滑肌瘤病(LAM)是一种罕见的肺部肿瘤,临床上与呼吸困难和呼吸衰竭相关。目前的治疗方式不一定达到令人满意的结果,目前需要新的治疗方法。因此,在这项研究中,我们集中于血管抑制素-1(VASH1)和-2(VASH2);VASH1终止,VASH2促进血管生成.此外,据报道,两种VASH1/2均影响各种人类恶性肿瘤的进展.我们首先进行层次聚类分析,试图根据VASH1/2的免疫反应性和LAM的其他血管生成和预后因素将36例LAM分为三个不同的簇;VEGFR1/2/3,p-mTOR,p-S6,p-4EBP,ERα,PgR,MMP2和MMP9。具有较高血管生成因子的簇具有较高的VASH1/2状态。VASH1与VEGFR2、MMP9、p-mTOR呈显著正相关(p值<0.05),和VASH2与血管生成和预后因素,包括VEGFR1,PgR,MMP9,p-mTOR,p-S6和p-4EBP(p值<0.05)。随后的血管生成基因的PCR阵列表明,高VASH1mRNA与SPHK1和TYPM的状态显著正相关,较低的EGF和EFNB2(p值<0.05),和高VASH2mRNA与MMP2呈阴性(p值<0.05)。VASH1被认为是通过激活血管生成而上调的,而VASH2可以影响LAM的血管生成和进展。
Lymphangioleiomyomatosis (LAM) is a rare pulmonary neoplasm, clinically associated with dyspnea and respiratory failure. Current therapeutic modalities do not necessarily reach satisfactory outcome and novel therapeutic approaches are currently warranted. Therefore, in this study, we focused on vasohibin-1 (VASH1) and -2 (VASH2); VASH1 terminated and VASH2 promoted angiogenesis. In addition, both VASH1/2 were reported to influence the progression of various human malignancies. We first performed hierarchical clustering analysis to attempt to classify 36 LAM cases into three different clusters according to immunoreactivity of VASH1/2 and other angiogenic and prognostic factors of LAM; VEGFR1/2/3, p-mTOR, p-S6, p-4EBP, ERα, PgR, MMP2, and MMP9. The cluster harboring higher angiogenic factors had higher VASH1/2 status. VASH1 was significantly positively correlated with VEGFR2, MMP9, and p-mTOR (p-value <0.05), and VASH2 with both angiogenic and prognostic factors including VEGFR1, PgR, MMP9, p-mTOR, p-S6, and p-4EBP (p-value <0.05). Subsequent PCR array of angiogenic genes demonstrated that high VASH1 mRNA was significantly positively associated with the status of SPHK1 and TYPM, lower EGF and EFNB2 (p-value <0.05), and high VASH2 mRNA negatively with MMP2 (p-value <0.05). VASH1 was considered to be up-regulated by activation of angiogenesis, whereas VASH2 could influence the angiogenesis and progression of LAM.