來自第二軍醫(yī)大學(xué)的研究人員在新研究中揭示了一種與肝癌微血管浸潤相關(guān)的長(zhǎng)鏈非編碼RNA,，以及其促進(jìn)血管生成的分子機(jī)制，這一RNA或可作為肝癌患者肝切除術(shù)后患者無復(fù)發(fā)的生存率不良的預(yù)測(cè)因子,。相關(guān)論文發(fā)表在相關(guān)論文發(fā)表在國際著名肝臟疾病雜志Hepatology上（最新影響因子11.665）上。
第二軍醫(yī)大學(xué)的孫樹漢（Shuhan Sun）教授和周偉平（Wei-Ping Zhou）是這篇論文的共同通訊作者,。前者的主要研究方向?yàn)榉肿舆z傳學(xué)研究,，近年來共發(fā)表科研論文210余篇（其中SCI收錄論文80余篇）。后者科研主攻方向是肝臟腫瘤的臨床治療及術(shù)后抗復(fù)發(fā)治療研究,。
血管生成,，即新生血管形成的過程,，被認(rèn)為是腫瘤生長(zhǎng)的關(guān)鍵因素,，不僅為腫瘤提供營養(yǎng)和氧氣，更是腫瘤細(xì)胞進(jìn)入系統(tǒng)循環(huán)和轉(zhuǎn)移的通路,。早在1971年,，F(xiàn)olkman教授就提出腫瘤生長(zhǎng)依賴于血管形成的學(xué)說，并認(rèn)為腫瘤的血管發(fā)生有可能成為抗腫瘤治療的靶點(diǎn),。
肝癌是典型的富血管腫瘤,。它的發(fā)生,、發(fā)展和轉(zhuǎn)移時(shí)時(shí)刻刻離不開腫瘤新生血管,。人們認(rèn)為肝癌患者的生存較差很大程度上是由于異常活躍的血管生成所致,。然而當(dāng)前對(duì)于肝癌的血管生成機(jī)制仍知之甚少,。
在這篇文章中，研究人員發(fā)現(xiàn)了一種與肝癌微血管浸潤相關(guān)的長(zhǎng)鏈非編碼RNA(lncRNA MVIH)在肝癌中普遍過表達(dá),。在215名肝癌患者中,，研究人員證實(shí)MVIH過表達(dá)與頻繁的微血管浸潤及較高的腫瘤淋巴結(jié)轉(zhuǎn)移階段，以及無復(fù)發(fā)生存率下降有關(guān),。并且,，MVIH上調(diào)可作為一個(gè)獨(dú)立的風(fēng)險(xiǎn)因子預(yù)測(cè)無復(fù)發(fā)生存率不良。
研究人員還在小鼠模型中證實(shí),，MVIH可以通過啟動(dòng)血管發(fā)生從而促進(jìn)腫瘤生長(zhǎng)以及肝內(nèi)轉(zhuǎn)移,。隨后進(jìn)一步的研究表明MVIH有可能通過抑制磷酸甘油酸激酶1(Phosphoglycerate kinase1，PGK1)促進(jìn)了腫瘤誘導(dǎo)的血管生成,。此外,，在65個(gè)肝癌樣本中，研究人員證實(shí)MVIH的表達(dá)與PGK1血清水平負(fù)相關(guān),，與微血管密度正相關(guān),。
這些研究結(jié)果表明lncRNA MVIH失控可作為肝切除術(shù)后肝癌患者無復(fù)發(fā)生存率不良的一個(gè)預(yù)測(cè)因子,，并為對(duì)抗異常活躍的血管生成提供了一種新輔助治療的潛在靶點(diǎn),。(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.
