来自第二军医大学的研究人员在新研究中揭示了一种与肝癌微血管浸润相关的长链非编码RNA，以及其促进血管生成的分子机制，这一RNA或可作为肝癌患者肝切除术后患者无复发的生存率不良的预测因子。相关论文发表在相关论文发表在国际著名肝脏疾病杂志Hepatology上（最新影响因子11.665）上。
第二军医大学的孙树汉（Shuhan Sun）教授和周伟平（Wei-Ping Zhou）是这篇论文的共同通讯作者。前者的主要研究方向为分子遗传学研究，近年来共发表科研论文210余篇（其中SCI收录论文80余篇）。后者科研主攻方向是肝脏肿瘤的临床治疗及术后抗复发治疗研究。
血管生成，即新生血管形成的过程，被认为是肿瘤生长的关键因素，不仅为肿瘤提供营养和氧气，更是肿瘤细胞进入系统循环和转移的通路。早在1971年，Folkman教授就提出肿瘤生长依赖于血管形成的学说，并认为肿瘤的血管发生有可能成为抗肿瘤治疗的靶点。
肝癌是典型的富血管肿瘤。它的发生、发展和转移时时刻刻离不开肿瘤新生血管。人们认为肝癌患者的生存较差很大程度上是由于异常活跃的血管生成所致。然而当前对于肝癌的血管生成机制仍知之甚少。
在这篇文章中，研究人员发现了一种与肝癌微血管浸润相关的长链非编码RNA(lncRNA MVIH)在肝癌中普遍过表达。在215名肝癌患者中，研究人员证实MVIH过表达与频繁的微血管浸润及较高的肿瘤淋巴结转移阶段，以及无复发生存率下降有关。并且，MVIH上调可作为一个独立的风险因子预测无复发生存率不良。
研究人员还在小鼠模型中证实，MVIH可以通过启动血管发生从而促进肿瘤生长以及肝内转移。随后进一步的研究表明MVIH有可能通过抑制磷酸甘油酸激酶1(Phosphoglycerate kinase1，PGK1)促进了肿瘤诱导的血管生成。此外，在65个肝癌样本中，研究人员证实MVIH的表达与PGK1血清水平负相关，与微血管密度正相关。
这些研究结果表明lncRNA MVIH失控可作为肝切除术后肝癌患者无复发生存率不良的一个预测因子，并为对抗异常活跃的血管生成提供了一种新辅助治疗的潜在靶点。(生物谷Bioon.com)
DOI: 10.1002/hep.25895
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Long noncoding RNA associated with microvascular invasion in hepatocellular carcinoma promotes angiogenesis and serves as a predictor for hepatocellular carcinoma patients' poor recurrence-free survival after hepatectomy
Sheng-Xian Yuan1,§, Fu Yang2,§,¶, Yuan Yang1,Qi-Fei Tao1, Jin Zhang1, Gang Huang1, Yun Yang1, Ruo-Yu Wang1, Sen Yang1, Xi-Song Huo2,Ling Zhang2, Fang Wang2, Shu-Han Sun2, Wei-Ping Zhou1,*
Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active angiogenesis. However, the mechanisms underlying angiogenesis in HCC remain to be discovered. In this study, we found that long noncoding RNA associated with microvascular invasion in HCC (lncRNA MVIH) (lncRNA associated with microvascular invasion in HCC) was generally overexpressed in HCC. In a cohort of 215 HCC patients, the overexpression of MVIH was associated with frequent microvascular invasion (P = 0.016) and a higher tumor node metastasis stage (P = 0.009) as well as decreased recurrence-free survival (RFS) (P < 0.001) and overall survival (P = 0.007). Moreover, the up-regulation of MVIH served as an independent risk factor to predict poor RFS. We also found that MVIH could promote tumor growth and intrahepatic metastasis by activating angiogenesis in mouse models. Subsequent investigations indicated that MVIH could activate tumor-inducing angiogenesis by inhibiting the secretion of phosphoglycerate kinase 1 (PGK1). Additionally, in 65 HCC samples, MVIH expression was inversely correlated with the serum level of PGK1 and positively correlated with the microvessel density. Conclusion: Deregulation of lncRNA MVIH is a predictor for poor RFS of HCC patients after hepatectomy and could be utilized as a potential target for new adjuvant therapies against active angiogenesis.
