In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA.
In situ measurement of miR-205 in malignant melanoma tissue supports its role as a tumor suppressor microRNA.
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DOI：
10.1038/labinvest.2012.119
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发表时间：
2012-10
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影响因子：
--
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致癌性和肿瘤抑制性miRNA已经成为包括黑色素瘤在内的许多类型癌症中基因表达的关键调节因子。我们利用定量原位杂交（qISH）来评估miRNA（miR-205）在人类肿瘤群体中的肿瘤抑制特性。我们假设减少的miR-205将与更具侵袭性的肿瘤相关。将miR-205 qISH与S100/GP 100的免疫荧光评估复合，使我们能够使用定量免疫荧光的AQUA方法定量评估miR-205表达。使用阻断寡核苷酸和转染的细胞系作为对照，验证了测定的特异性。对由105例原发性黑色素瘤标本组成的耶鲁黑色素瘤发现队列（Yale Melanoma Discovery Cohort）进行了结局评估，并对206例原发性黑色素瘤（Yale Melanoma Validation Cohort）进行了独立验证。黑色素瘤细胞miR-205水平的测量显示低表达患者的黑色素瘤特异性生存期显著缩短。多变量分析显示miR-205水平显著独立于分期、年龄、性别和Breslow深度。通过ISH定量的黑色素瘤细胞miR-205表达水平较低，显示出更差的结果，支持miR-205作为肿瘤抑制因子miRNA的作用。miR 205的原位定量表明miRNAs在未来预后或预测模型中的应用潜力。
Oncogenic and tumor suppressing miRNAs have emerged as key regulators of gene expression in many types of cancer including melanoma. We utilized quantitative in situ hybridization (qISH) to evaluate the tumor suppressing properties of miRNA, miR-205 in a population of human tumors. We hypothesize decreased miR-205 would be associated with more aggressive tumors. Multiplexing miR-205 qISH with immunofluorescent assessment of S100/GP100 allowed us to quantitatively evaluate miR-205 expression using the AQUA method of quantitative immunofluorescence. The specificity of the assay was validated using blocking oligos and transfected cell lines as controls. Outcomes were assessed on the Yale Melanoma Discovery Cohort consisting of 105 primary melanoma specimens and validated on an independent set of 206 primary melanomas (Yale Melanoma Validation Cohort). Measurement of melanoma cell miR-205 levels shows a significantly shorter melanoma specific survival in patients with low expression. Multivariate analysis shows miR-205 levels are significantly independent of stage, age, gender and Breslow depth. Low levels of melanoma cell miR-205 expression as quantified by ISH show worse outcome, supporting the role of miR-205 as a tumor suppressor miRNA. The quantification of miR205 in situ suggests potential for the use of miRNAs in future prognostic or predictive models.
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影响因子：
6.2
作者：
Majid, Shahana;Dar, Altaf A.;Saini, Sharanjot;Yamamura, Soichiro;Hirata, Hiroshi;Tanaka, Yuichiro;Deng, Guoren;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
2.7
作者：
Hanna JA;Wimberly H;Kumar S;Slack F;Agarwal S;Rimm DL
通讯作者：
Rimm DL
DOI：
10.1158/1078-0432.ccr-10-1152
发表时间：
2010-08-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Sempere LF;Preis M;Yezefski T;Ouyang H;Suriawinata AA;Silahtaroglu A;Conejo-Garcia JR;Kauppinen S;Wells W;Korc M
通讯作者：
Korc M
影响因子：
11.2
作者：
Gandellini, Paolo;Folini, Marco;Zaffaroni, Nadia
通讯作者：
Zaffaroni, Nadia
DOI：
10.1016/j.urolonc.2007.01.019
发表时间：
2007-09-01
影响因子：
2.7
作者：
Gottardo, Fedra;Liu, Chang Gong;Baffa, Raffaele
通讯作者：
Baffa, Raffaele