宫颈小细胞癌(small cell carcinoma of the cervix,SCCC)是一种罕见而独特的妇科高度恶性肿瘤,是最具侵袭力的妇科恶性肿瘤之一。近日,中国中山大学的王辉云等人对SCCC开展了一项有意义的研究。研究发现几种SCCC晚期下调的miRNA与癌细胞转移以及不良预后有关,相关研究发表在3月16日的美国《公共科学图书馆·综合》(PLoS ONE)上。
宫颈小细胞癌(SCCC) 非常罕见,由于需要长期的招募足够数量的病人,关于幸存者预后因素的信息非常缺乏。在很多类型的癌症中,miRNAs已经被用作生物标记,该项研究的目的就是为了确定miRNAs的表达谱是否可以预测SCCC的临床结果。
有44个经历了子宫根除手术的SCCC病人在2000年1月至2009年9月年间接受调查。对这些病人石蜡嵌入福尔马林固定的样品,用All-in-One qPCR Primer Array分析得知,有30种miRNAs与癌症转移有关。与早期 SCCC病人相比,晚期SCCC病人的样品中有七种miRNA都被明显的下调,它们是 has-let-7c、has-miR-10b、has-miR-100、has-miR-125b、has-miR-143、 has-miR-145 和 has-miR-199a-5p。
其中,六种miRNAs(has-let-7c、has-miR-100、has-miR-125b、has-miR-143、has-miR-145 及has-miR-199a-5p)明显与淋巴结转移以及降低SCCC生存有关。Kaplan–Meier生存曲线分析显示,低表达的has-miR-100(P=0.019)及has-miR-125b(P=0.020)的SCCC病人会导致明显的预后不佳。
这项研究证明,SCCC晚期七种下调的miRNA,有种六种miRNA与转移有关,两种与不良预后有关。对这些miRNA的功能性分析可能会增进我们对SCCC的了解。并且,改变特异的miRNA的表达,很可能会调节癌细胞转移路径,也为治疗SCCC提供了一个新的靶点。(生物谷Bioon.com)
doi: 10.1371/journal.pone.0033762
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Downregulation of Six MicroRNAs Is Associated with Advanced Stage, Lymph Node Metastasis and Poor Prognosis in Small Cell Carcinoma of the Cervix
Long Huang, Jia-Xin Lin, Yan-Hong Yu, Mei-Yin Zhang, Hui-Yun Wang, Min Zheng.
Small cell carcinoma of the cervix (SCCC) is very rare, and due to the long time period required to recruit sufficient numbers of patients, there is a paucity of information regarding the prognostic factors associated with survival. MicroRNAs (miRNAs) have been used as cancer-related biomarkers in a variety of tumor types, and the objective of this study was to determine whether microRNA expression profiles can predict clinical outcome in SCCC.Forty-four patients with SCCC who underwent radical hysterectomy between January 2000 and October 2009 were enrolled. Using the GeneCopoeia All-in-One Customized Human qPCR Primer Array, the expression profiles of 30 miRNAs associated with tumor metastasis was obtained from the formalin-fixed paraffin embedded samples of all 44 patients. Seven miRNAs, has-let-7c, has-miR-10b, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were ignificantly down-regulated in advanced stage SCCCpatients (FIGO IB2-IV) compared to early stage SCCC patients (FIGOIB1).Among, downregulation of six miRNAs, has-let-7c, has-miR-100, has-miR-125b, has-miR-143, has-miR-145 and has-miR-199a-5p were significantly associated with lymph node metastasis and reduced survival in SCCC. Kaplan–Meier survival analyses revealed that SCCC patients with low expression of has-miR-100 (P = 0.019) and has-miR-125b (P = 0.020) projected a significant tendency towards poorer prognosis.This study demonstrates that downregulation of 7 miRNA associated with advanced stage, 6 miRNAs with metastasis and 2 with poor prognosis in SCCC. Functional analysis of these miRNAs may enhance our understanding of SCCC, as altered expression of specific miRNAs may regulate the metastatic pathway and provide novel targets for therapy.n.