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基于简约系统发育分析的胰腺导管腺癌样本临床生存及基因表达研究

Study of Clinical Survival and Gene Expression in a Sample of Pancreatic Ductal Adenocarcinoma by Parsimony Phylogenetic Analysis.

作者信息

Nalbantoglu Sinem, Abu-Asab Mones, Tan Ming, Zhang Xuemin, Cai Ling, Amri Hakima

机构信息

1 Department of Biochemistry, Cellular and Molecular Biology, School of Medicine, Georgetown University , Washington, DC.

2 Laboratory of Immunology, Section of Immunopathology, National Eye Institute , Bethesda, Maryland.

出版信息

OMICS. 2016 Jul;20(7):442-7. doi: 10.1089/omi.2016.0059.

DOI:10.1089/omi.2016.0059
PMID:27428255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4968342/
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the rapidly growing forms of pancreatic cancer with a poor prognosis and less than 5% 5-year survival rate. In this study, we characterized the genetic signatures and signaling pathways related to survival from PDAC, using a parsimony phylogenetic algorithm. We applied the parsimony phylogenetic algorithm to analyze the publicly available whole-genome in silico array analysis of a gene expression data set in 25 early-stage human PDAC specimens. We explain here that the parsimony phylogenetics is an evolutionary analytical method that offers important promise to uncover clonal (driver) and nonclonal (passenger) aberrations in complex diseases. In our analysis, parsimony and statistical analyses did not identify significant correlations between survival times and gene expression values. Thus, the survival rankings did not appear to be significantly different between patients for any specific gene (p > 0.05). Also, we did not find correlation between gene expression data and tumor stage in the present data set. While the present analysis was unable to identify in this relatively small sample of patients a molecular signature associated with pancreatic cancer prognosis, we suggest that future research and analyses with the parsimony phylogenetic algorithm in larger patient samples are worthwhile, given the devastating nature of pancreatic cancer and its early diagnosis, and the need for novel data analytic approaches. The future research practices might want to place greater emphasis on phylogenetics as one of the analytical paradigms, as our findings presented here are on the cusp of this shift, especially in the current era of Big Data and innovation policies advocating for greater data sharing and reanalysis.

摘要

胰腺导管腺癌(PDAC)是胰腺癌中增长迅速的一种形式,预后较差,5年生存率低于5%。在本研究中,我们使用简约系统发育算法,对与PDAC生存相关的基因特征和信号通路进行了表征。我们应用简约系统发育算法,对25例早期人类PDAC标本的基因表达数据集进行公开可用的全基因组计算机阵列分析。我们在此解释,简约系统发育学是一种进化分析方法,有望揭示复杂疾病中的克隆(驱动)和非克隆(乘客)畸变。在我们的分析中,简约分析和统计分析未发现生存时间与基因表达值之间存在显著相关性。因此,对于任何特定基因,患者之间的生存排名似乎没有显著差异(p>0.05)。此外,在本数据集中,我们未发现基因表达数据与肿瘤分期之间存在相关性。虽然目前的分析未能在这个相对较小的患者样本中识别出与胰腺癌预后相关的分子特征,但考虑到胰腺癌的毁灭性本质及其早期诊断,以及对新型数据分析方法的需求,我们建议未来在更大的患者样本中使用简约系统发育算法进行研究和分析是值得的。未来的研究实践可能希望更加强调系统发育学作为分析范式之一,因为我们在此呈现的研究结果正处于这一转变的前沿,尤其是在当前倡导更大数据共享和重新分析的大数据和创新政策时代。

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本文引用的文献

1
Functional annotation of rare gene aberration drivers of pancreatic cancer.胰腺癌罕见基因畸变驱动因素的功能注释
Nat Commun. 2016 Jan 25;7:10500. doi: 10.1038/ncomms10500.
2
Computational Tools for Parsimony Phylogenetic Analysis of Omics Data.用于组学数据简约系统发育分析的计算工具
OMICS. 2015 Aug;19(8):471-7. doi: 10.1089/omi.2015.0018. Epub 2015 Jun 3.
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A multi-gene signature predicts outcome in patients with pancreatic ductal adenocarcinoma.多基因标志物可预测胰腺导管腺癌患者的预后。
Genome Med. 2014 Dec 3;6(12):105. doi: 10.1186/s13073-014-0105-3. eCollection 2014.
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PLoS One. 2014 Sep 2;9(9):e105631. doi: 10.1371/journal.pone.0105631. eCollection 2014.
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Downstream of mutant KRAS, the transcription regulator YAP is essential for neoplastic progression to pancreatic ductal adenocarcinoma.突变型 KRAS 下游的转录调节因子 YAP 对于胰腺导管腺癌的肿瘤进展是必需的。
Sci Signal. 2014 May 6;7(324):ra42. doi: 10.1126/scisignal.2005049.
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Upregulated SMAD3 promotes epithelial-mesenchymal transition and predicts poor prognosis in pancreatic ductal adenocarcinoma.SMAD3 的上调促进了胰腺导管腺癌的上皮-间充质转化,并预示着不良的预后。
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Pathway-gene identification for pancreatic cancer survival via doubly regularized Cox regression.通过双重正则化Cox回归识别胰腺癌生存的通路基因
BMC Syst Biol. 2014;8 Suppl 1(Suppl 1):S3. doi: 10.1186/1752-0509-8-S1-S3. Epub 2014 Jan 24.
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Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.局部进展期胰腺癌:术前治疗时间延长与淋巴结阴性和总生存的关系。
JAMA Surg. 2014 Feb;149(2):145-53. doi: 10.1001/jamasurg.2013.2690.
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Understanding pancreatic cancer genomes.了解胰腺癌基因组。
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Identifying early events of gene expression in breast cancer with systems biology phylogenetics.利用系统生物学系统发育学识别乳腺癌基因表达的早期事件。
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