Pancreatic cancer survival analysis defines a signature that predicts outcome.
Pancreatic cancer survival analysis defines a signature that predicts outcome.
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DOI：
10.1371/journal.pone.0201751
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Tozeren A
中科院分区：
文献类型：
--
作者：
Raman P;Maddipati R;Lim KH;Tozeren A
胰腺导管腺癌（PDAC）是美国癌症死亡的第三大原因。尽管进行了多项大规模基因测序研究，但确定患者生存的预测因素仍然具有挑战性。我们在多个平台上对大规模基因表达数据集进行了全面评估和综合分析，以发现胰腺癌患者生存的预后基因特征。将来自癌症基因组图谱的PDAC RNA测序数据分层为存活+（>2年存活）和存活-（<1年存活）群组（n = 47）。比较存活组和来自基因表达综合数据库的正常胰腺组织表达数据之间的RNA表达谱，产生初始PDAC特异性预后差异表达基因列表。然后使用基于迭代采样的算法，在来自ICGC数据库的澳大利亚胰腺癌数据集（n = 103）上训练候选预后基因列表，以导出预测患者存活的基因签名。在2个独立的患者队列中并针对现有的PDAC亚型分类验证了基因签名。我们确定了707个候选预后基因在肿瘤和正常组织中表现出差异表达。这些基因的相当大一部分也被发现在存活组之间差异甲基化。从候选基因列表中，鉴定了5个基因标签（ADM、ASPM、DCBLD 2、E2 F7和KRT 6A）。我们的签名证明了在两个不同的患者队列中预测患者生存的显著能力，并且独立于AJCC TNM分期。与现有的PDAC生存特征相比，我们的基因特征的交叉验证报告了更好的ROC AUC（≥ 0.8）。此外，通过对患者肿瘤组织的免疫组织化学分析和PDAC中现有基因表达亚型数据验证我们的签名，证明了与血管浸润和侵袭性鳞状肿瘤亚型的存在相关。在患者活检中评估这些基因有助于进一步为胰腺癌的风险分层和治疗决策提供信息。
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the US. Despite multiple large-scale genetic sequencing studies, identification of predictors of patient survival remains challenging. We performed a comprehensive assessment and integrative analysis of large-scale gene expression datasets, across multiple platforms, to enable discovery of a prognostic gene signature for patient survival in pancreatic cancer. PDAC RNA-Sequencing data from The Cancer Genome Atlas was stratified into Survival+ (>2-year survival) and Survival–(<1-year survival) cohorts (n = 47). Comparisons of RNA expression profiles between survival groups and normal pancreatic tissue expression data from the Gene Expression Omnibus generated an initial PDAC specific prognostic differential expression gene list. The candidate prognostic gene list was then trained on the Australian pancreatic cancer dataset from the ICGC database (n = 103), using iterative sampling based algorithms, to derive a gene signature predictive of patient survival. The gene signature was validated in 2 independent patient cohorts and against existing PDAC subtype classifications. We identified 707 candidate prognostic genes exhibiting differential expression in tumor versus normal tissue. A substantial fraction of these genes was also found to be differentially methylated between survival groups. From the candidate gene list, a 5-gene signature (ADM, ASPM, DCBLD2, E2F7, and KRT6A) was identified. Our signature demonstrated significant power to predict patient survival in two distinct patient cohorts and was independent of AJCC TNM staging. Cross-validation of our gene signature reported a better ROC AUC (≥ 0.8) when compared to existing PDAC survival signatures. Furthermore, validation of our signature through immunohistochemical analysis of patient tumor tissue and existing gene expression subtyping data in PDAC, demonstrated a correlation to the presence of vascular invasion and the aggressive squamous tumor subtype. Assessment of these genes in patient biopsies could help further inform risk-stratification and treatment decisions in pancreatic cancer.
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美国癌症联合委员会多机构验证研究（第 8 版）胰腺癌患者 T 和 N 分期的变化。
影响因子：
9
作者：
Allen PJ;Kuk D;Castillo CF;Basturk O;Wolfgang CL;Cameron JL;Lillemoe KD;Ferrone CR;Morales-Oyarvide V;He J;Weiss MJ;Hruban RH;Gönen M;Klimstra DS;Mino-Kenudson M
通讯作者：
Mino-Kenudson M
影响因子：
29.4
作者：
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通讯作者：
Chari ST
影响因子：
6.4
作者：
Keleg, Shereen;Kayed, Hany;Kleeff, Joerg
通讯作者：
Kleeff, Joerg
影响因子：
5.8
作者：
Bikeye SN;Colin C;Marie Y;Vampouille R;Ravassard P;Rousseau A;Boisselier B;Idbaih A;Calvo CF;Leuraud P;Lassalle M;El Hallani S;Delattre JY;Sanson M
通讯作者：
Sanson M
DOI：
10.1158/1078-0432.ccr-14-2022
发表时间：
2015-04-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Javeed N;Sagar G;Dutta SK;Smyrk TC;Lau JS;Bhattacharya S;Truty M;Petersen GM;Kaufman RJ;Chari ST;Mukhopadhyay D
通讯作者：
Mukhopadhyay D