Differentiating progressive from nonprogressive T1 bladder cancer by gene expression profiling: applying RNA-sequencing analysis on archived specimens.
Differentiating progressive from nonprogressive T1 bladder cancer by gene expression profiling: applying RNA-sequencing analysis on archived specimens.
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DOI：
10.1016/j.urolonc.2013.06.014
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发表时间：
2014-04
期刊：
影响因子：
--
通讯作者：
Scott McDougal W
中科院分区：
文献类型：
--
作者：
Sharron Lin X;Hu L;Sandy K;Correll M;Quackenbush J;Wu CL;Scott McDougal W
确定移行细胞癌中可以区分高级别T1非进展性（T1 NP）膀胱癌（BCa）与进展为肌层浸润性T2肿瘤的T1进展性（T1 P）肿瘤的基因特征。我们对福尔马林固定和石蜡包埋的BCa标本进行了高通量RNA测序（RNA-Seq），其临床病理特征最能代表疾病的一般临床发展。对于T1 NP组，仅选择长期随访（6-17年）和定期检查（平均4次切除和9次细胞学检查）的患者。对于T1 P组，仅选择在初始T1诊断后至少8个月后进行完全切除的患者，因此消除了诊断不足的可能性。仅包括存在固有肌层且未受累的样本，以进一步确保正确诊断。使用TopHat将RNA-Seq读段映射到人类基因组构建NCBI 36（hgl 8），没有错配。在与转录组比对和表达定量后，使用Limma在T1 NP和T1 P样品之间建立线性统计模型以鉴定差异表达的基因。总的来说，5，561个基因被映射到所有样本中，并用于RNA-Seq分析，以鉴定T1 NP BCa患者和T1 P BCa患者之间显著差异表达的基因特征。基于信号的分层表明基因信号与T1发展为T2肿瘤的时间显著相关，表明分子信号可用作高级别T1 BCa进展速度的独立预测因子。这是第一次证明RNA-Seq可以作为一个强大的工具，使用福尔马林固定和石蜡包埋标本研究BCa。我们确定了一个基因特征，可以区分诊断为高级别T1 BCas的患者，这些患者仍然是非肌肉浸润性肿瘤，而这些患者的癌症进展为肌肉浸润性肿瘤。我们的研究结果将使未来的大规模临床队列研究和基于临床试验的研究成为可能，并有助于开发准确预测T1 BCa进展的预后工具，这可能会极大地影响临床决策过程、治疗方案和患者生存。
To identify gene signatures in transitional cell carcinoma that can differentiate high-grade T1 nonprogressive (T1NP) bladder cancer (BCa) from those T1 progressive (T1P) tumors that progress to muscularis propria–invasive T2 tumors. We performed a high-throughput RNA sequencing (RNA-Seq) on formalin-fixed and paraffin-embedded BCa specimens with clinical pathologic characteristics best representing the general clinical development of the disease. For the T1NP group, only patients with long-term follow-up (6–17 y) and periodic examinations (average of 4 resections and 9 cytology tests) were selected. For the T1P group, only patients in whom a complete resection was performed after a minimum of 8 months after the initial T1 diagnosis were selected, therefore eliminating the possibility of underdiagnosis. Only samples in which muscularis propria was present and uninvolved were included, further assuring a correct diagnosis. The RNA-Seq reads were mapped to the human genome build NCBI 36 (hg18) using TopHat with no mismatch. After alignment to the transcriptome and expression quantification, a linear statistical model was built using Limma between T1NP and T1P samples to identify differentially expressed genes. Overall, 5,561 genes were mapped to all samples and used for RNA-Seq analysis to identify a gene signature that was significantly and differentially expressed between patients with T1NP BCa and patients with T1P BCa. Signature-based stratification indicated the gene signature correlated notably with the time of T1 development to T2 tumor, suggesting that the molecular signature might be used as an independent predictor for the pace of high-grade T1 BCa progression. This is the first demonstration that RNA-Seq can be applied as a powerful tool to study BCa using formalin-fixed and paraffin-embedded specimens. We identified a gene signature that can distinguish patients diagnosed with high-grade T1 BCas that remain as non–muscle invasive tumors from those patients with cancers progressing to muscle-invasive tumors. Our findings will make future large-scale clinical cohort studies and clinical trial–based studies possible and help the development of prognostic tools for accurate prediction of T1 BCa progression that may considerably influence the clinical decision–making process, treatment regimen, and patient survival.
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RNA-Seq 分析生成全面的转录组景观并揭示肝细胞癌中复杂的转录模式。
影响因子：
3.7
作者：
Huang Q;Lin B;Liu H;Ma X;Mo F;Yu W;Li L;Li H;Tian T;Wu D;Shen F;Xing J;Chen ZN
通讯作者：
Chen ZN
影响因子：
46.9
作者：
Trapnell C;Williams BA;Pertea G;Mortazavi A;Kwan G;van Baren MJ;Salzberg SL;Wold BJ;Pachter L
通讯作者：
Pachter L
影响因子：
56.9
作者：
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通讯作者：
Lander, ES
影响因子：
11.5
作者：
Blaveri, E;Brewer, JL;Waldman, FM
通讯作者：
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影响因子：
6.4
作者：
Wiklund, Erik D.;Bramsen, Jesper B.;Clark, Susan J.
通讯作者：
Clark, Susan J.