MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32.
MicroRNA paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32.
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DOI：
10.1186/gm406
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发表时间：
2013
期刊：
影响因子：
12.3
通讯作者：
Spentzos D
中科院分区：
文献类型：
--
作者：
Kelly AD;Haibe-Kains B;Janeway KA;Hill KE;Howe E;Goldsmith J;Kurek K;Perez-Atayde AR;Francoeur N;Fan JB;April C;Schneider H;Gebhardt MC;Culhane A;Quackenbush J;Spentzos D
尽管 microRNA (miRNA) 与骨肉瘤生物学和化疗反应有关，但仍然需要 miRNA 预后模型，特别是因为预后与化疗反应不完全相关。福尔马林固定、石蜡包埋的组织是这种恶性肿瘤生物标志物研究的必要资源，但冷冻组织的可用性有限。我们对 65 个骨肉瘤活检样本和 26 个配对的化疗后切除样本进行了 miRNA 和 mRNA 微阵列福尔马林固定、石蜡包埋检测，并使用由另一组独立生成的唯一公开可用的 miRNA 数据集，从外部验证了我们最有力的发现 (n = 29)。我们使用监督主成分分析和逻辑回归来研究生存和化学反应，并使用 miRNA 活性和靶基因集分析来研究 miRNA 调控活性。几种基于 miRNA 的模型（只有 5 个 miRNA）的预后独立于病理评估的化学反应（中位无复发生存期：59 个月与尚未达到；调整后的风险比 = 2.90；P = 0.036）。独立数据集支持复发和生存结果的可重复性。该谱的预后价值独立于已知预后变量的混杂，包括化学反应、肿瘤位置和诊断时的转移。当添加化学反应作为协变量时，模型性能得到改善（中位无复发生存期：59 个月与尚未达到；风险比 = 3.91；P = 0.002）。大多数预后 miRNA 位于 14q32（该位点已与骨肉瘤相关），它们的基因靶点显示出与结果相关的失调模式。我们还确定了预测化学反应的 miRNA 谱（准确度为 75% 至 80%），其与预后谱不重叠。福尔马林固定、石蜡包埋的组织来源的 miRNA 模式是风险分层骨肉瘤管理策略的强大预后工具。 miRNA 和 mRNA 联合分析支持 14q32 位点在骨肉瘤进展和结果中可能发挥的作用。我们的研究为福尔马林固定、石蜡包埋的癌症 miRNA 生物标志物研究创建了一个范例。
Although microRNAs (miRNAs) are implicated in osteosarcoma biology and chemoresponse, miRNA prognostic models are still needed, particularly because prognosis is imperfectly correlated with chemoresponse. Formalin-fixed, paraffin-embedded tissue is a necessary resource for biomarker studies in this malignancy with limited frozen tissue availability. We performed miRNA and mRNA microarray formalin-fixed, paraffin-embedded assays in 65 osteosarcoma biopsy and 26 paired post-chemotherapy resection specimens and used the only publicly available miRNA dataset, generated independently by another group, to externally validate our strongest findings (n = 29). We used supervised principal components analysis and logistic regression for survival and chemoresponse, and miRNA activity and target gene set analysis to study miRNA regulatory activity. Several miRNA-based models with as few as five miRNAs were prognostic independently of pathologically assessed chemoresponse (median recurrence-free survival: 59 months versus not-yet-reached; adjusted hazards ratio = 2.90; P = 0.036). The independent dataset supported the reproducibility of recurrence and survival findings. The prognostic value of the profile was independent of confounding by known prognostic variables, including chemoresponse, tumor location and metastasis at diagnosis. Model performance improved when chemoresponse was added as a covariate (median recurrence-free survival: 59 months versus not-yet-reached; hazard ratio = 3.91; P = 0.002). Most prognostic miRNAs were located at 14q32 - a locus already linked to osteosarcoma - and their gene targets display deregulation patterns associated with outcome. We also identified miRNA profiles predictive of chemoresponse (75% to 80% accuracy), which did not overlap with prognostic profiles. Formalin-fixed, paraffin-embedded tissue-derived miRNA patterns are a powerful prognostic tool for risk-stratified osteosarcoma management strategies. Combined miRNA and mRNA analysis supports a possible role of the 14q32 locus in osteosarcoma progression and outcome. Our study creates a paradigm for formalin-fixed, paraffin-embedded-based miRNA biomarker studies in cancer.
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DOI：
10.1158/1078-0432.ccr-09-1631
发表时间：
2009-11-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Conway C;Mitra A;Jewell R;Randerson-Moor J;Lobo S;Nsengimana J;Edward S;Sanders DS;Cook M;Powell B;Boon A;Elliott F;de Kort F;Knowles MA;Bishop DT;Newton-Bishop J
通讯作者：
Newton-Bishop J
影响因子：
14.9
作者：
Chen, Jing;Lozach, Jean;Wickham, Eliza;Barnes, Garcia Bret;Luo, Shujun;Mikoulitch, Ivan;Zhou, Lixin;Schroth, Gary;Fan, Jian-Bing
通讯作者：
Fan, Jian-Bing
DOI：
10.1016/j.bbrc.2009.07.101
发表时间：
2009-10-09
影响因子：
3.1
作者：
He, Chunlei;Xiong, Jianyi;Wang, Daping
通讯作者：
Wang, Daping
影响因子：
11.2
作者：
Jones KB;Salah Z;Del Mare S;Galasso M;Gaudio E;Nuovo GJ;Lovat F;LeBlanc K;Palatini J;Randall RL;Volinia S;Stein GS;Croce CM;Lian JB;Aqeilan RI
通讯作者：
Aqeilan RI
影响因子：
6.4
作者：
Gougelet, Angelique;Pissaloux, Daniel;Alberti, Laurent
通讯作者：
Alberti, Laurent