Genetic landscape of prognostic value in pancreatic ductal adenocarcinoma microenvironment
Genetic landscape of prognostic value in pancreatic ductal adenocarcinoma microenvironment
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DOI：
10.21037/atm.2019.10.91
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发表时间：
2019-11-01
影响因子：
--
通讯作者：
Wu, Wenchuan
中科院分区：
文献类型：
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作者：
Pu, Ning;Chen, Qiangda;Wu, Wenchuan
背景：胰腺导管腺癌（PDAC）的预后仍然很差，被广泛认为是一种复杂的遗传性疾病。PDAC的突变景观可以直接反映癌症免疫原性，并决定免疫细胞浸润的程度和表型。相反，微环境也可能影响癌细胞的基因表达，这与临床预后有关。因此，它是至关重要的，以确定基因组改变PDAC微环境及其对临床预后的影响。方法：基因表达谱，突变数据和临床信息的179例胰腺癌患者的初步病理诊断范围从2001年至2013年检索癌症基因组图谱（TCGA）数据库。结果：PDAC亚型的平均免疫评分和间质评分均显著高于其他亚型，PDAC亚型的平均免疫评分和间质评分均显著高于其他亚型。KRAS突变病例的免疫评分（P=0.001）和基质评分（P=0.007）显着降低，与TP 53突变病例的免疫评分较低（P=0.030）一致。SMAD 4和CDKN 2A基因突变的差异无统计学意义。在OS/RFS队列中，高基质评分组的CD 8 + T细胞、B细胞、巨噬细胞、中性粒细胞和DC浸润水平均高于低基质评分组（均P
Background: The prognosis of pancreatic ductal adenocarcinoma (PDAC) remains dismally poor and is widely considered as an intricate genetic disorder. The mutational landscape of PDAC may directly reflect cancer immunogenicity and dictate the extent and phenotype of immune cell infiltration. In adverse, the microenvironment may also effect the gene expression of cancer cells, which is associated with clinical prognosis. Thus, it is crucial to identify genomic alterations in PDAC microenvironment and its impacts on clinical prognosis.Methods: The gene expression profiles, mutation data and clinical information of 179 pancreatic cancer patients with an initial pathologic diagnosis ranging from 2001 to 2013 were retrieved from The Cancer Genome Atlas (TCGA) database. The MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm for calculating immune scores and stromal scores and Tumor IMmune Estimation Resource (TIMER) resource for cell infiltrations were applied in this study.Results: The average immune score or stromal score of PDAC subtype was significantly higher than that of other specific subtypes. KRAS mutant cases had significantly lower immune scores (P=0.001) and stromal scores (P=0.007), in concert with lower immune scores in TP53 mutant cases (P=0.030). However, no significant difference was found in SMAD4 and CDKN2A mutations. In the cohort OS/RFS, the infiltration levels of CD8+ T cells, B cells, Macrophages, Neutrophils and DCs in high stromal score group were higher than those in the low score group (all P