The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis.
The Impact of Immune Microenvironment on the Prognosis of Pancreatic Ductal Adenocarcinoma Based on Multi-Omics Analysis.
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DOI：
10.3389/fimmu.2021.769047
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发表时间：
2021
影响因子：
7.3
通讯作者：
Ma J
中科院分区：
文献类型：
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作者：
Yang B;Zhou M;Wu Y;Ma Y;Tan Q;Yuan W;Ma J
胰腺导管腺癌（PDAC）是一种恶性肿瘤，其特点是进展快、转移早、复发率高、对常规治疗反应有限。 PDAC的5年生存率极低（<8%），缺乏有效的预后评估指标。在本研究中，我们使用xCell分析肿瘤中的浸润免疫细胞，通过单变量和多变量Cox分析筛选出两种与预后相关的免疫细胞CD4+TN和共同淋巴祖细胞（CLP），用于构建Cox模型并计算出风险评分。结果发现，构建的模型可以大大提高预后评估的敏感性，风险评分越高，预后越差。此外，风险评分还可以识别预后不良和免疫治疗敏感性较差的分子亚型。通过对癌症基因组图谱（TCGA）PDAC数据集的转录组和全外显子组测序分析，发现CCL19的拷贝数缺失和低表达可能是影响风险评分的关键因素。最后，上述发现的验证不仅在基因表达综合 (GEO) 数据集中得到了证实，而且也在我们的 PDAC 患者样本 Peking2020 队列中得到了证实。
Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor characterized by rapid progression, early metastasis, high recurrence, and limited responsiveness to conventional therapies. The 5-year survival rate of PDAC is extremely low (<8%), which lacks effective prognostic evaluation indicators. In this study, we used xCell to analyze infiltrating immune cells in a tumor and through the univariate and multivariate Cox analyses screened out two prognosis-related immune cells, CD4+TN and common lymphoid progenitor (CLP), which were used to construct a Cox model and figure out the risk-score. It was found that the constructed model could greatly improve the sensitivity of prognostic evaluation, that the higher the risk-score, the worse the prognosis. In addition, the risk-score could also identify molecular subtypes with poor prognosis and immunotherapy sensitivity. Through transcriptome and whole-exome sequencing analysis of PDAC dataset from The Cancer Genome Atlas (TCGA), it was found that copy number deletion and low expression of CCL19 might be crucial factors to affect the risk-score. Lastly, validation of the above findings was confirmed not only in Gene Expression Omnibus (GEO) datasets but also in our PDAC patient samples, Peking2020 cohort.