宮頸小細胞癌(small cell carcinoma of the cervix,,SCCC)是一種罕見而獨特的婦科高度惡性腫瘤,,是最具侵襲力的婦科惡性腫瘤之一。近日,,中國中山大學的王輝云等人對SCCC開展了一項有意義的研究,。研究發(fā)現(xiàn)幾種SCCC晚期下調(diào)的miRNA與癌細胞轉(zhuǎn)移以及不良預(yù)后有關(guān),相關(guān)研究發(fā)表在3月16日的美國《公共科學圖書館·綜合》(PLoS ONE)上,。
宮頸小細胞癌(SCCC) 非常罕見,,由于需要長期的招募足夠數(shù)量的病人,關(guān)于幸存者預(yù)后因素的信息非常缺乏,。在很多類型的癌癥中,,miRNAs已經(jīng)被用作生物標記,該項研究的目的就是為了確定miRNAs的表達譜是否可以預(yù)測SCCC的臨床結(jié)果,。
有44個經(jīng)歷了子宮根除手術(shù)的SCCC病人在2000年1月至2009年9月年間接受調(diào)查,。對這些病人石蠟嵌入福爾馬林固定的樣品,用All-in-One qPCR Primer Array分析得知,,有30種miRNAs與癌癥轉(zhuǎn)移有關(guān),。與早期 SCCC病人相比,晚期SCCC病人的樣品中有七種miRNA都被明顯的下調(diào),,它們是 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,,六種miRNAs(has-let-7c、has-miR-100,、has-miR-125b,、has-miR-143、has-miR-145 及has-miR-199a-5p)明顯與淋巴結(jié)轉(zhuǎn)移以及降低SCCC生存有關(guān),。Kaplan–Meier生存曲線分析顯示,,低表達的has-miR-100(P=0.019)及has-miR-125b(P=0.020)的SCCC病人會導致明顯的預(yù)后不佳。
這項研究證明,,SCCC晚期七種下調(diào)的miRNA,,有種六種miRNA與轉(zhuǎn)移有關(guān),,兩種與不良預(yù)后有關(guān)。對這些miRNA的功能性分析可能會增進我們對SCCC的了解,。并且,,改變特異的miRNA的表達,很可能會調(diào)節(jié)癌細胞轉(zhuǎn)移路徑,,也為治療SCCC提供了一個新的靶點,。(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.