通过单细胞和大量 RNA 测序数据,确定了胰腺导管腺癌的关键预后信号通路。

IF 3.8 2区 生物学 Q2 GENETICS & HEREDITY
Human Genetics Pub Date : 2024-10-01 Epub Date: 2024-03-25 DOI:10.1007/s00439-024-02663-4
Wenwen Wang, Guo Chen, Wenli Zhang, Xihua Zhang, Manli Huang, Chen Li, Ling Wang, Zifan Lu, Jielai Xia
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引用次数: 0

摘要

胰腺导管腺癌(PDAC)是一种预后差、死亡率高的恶性肿瘤。尽管大量研究利用传统的RNA测序(RNA-Seq)数据探索了其潜在的预后标志物,但并未取得良好的预测效果。为了探索导致预后差异的可能预后信号通路,我们分别从一个scRNA-seq队列和四个GEO队列中发现了差异表达基因。然后,Cox 和 Lasso 回归分析表明,12 个基因是 PDAC 的独立预后因素。AUC和校准曲线分析表明,预后模型具有良好的区分度和校准性。与低风险组相比,高风险组的基因突变比例高于低风险组。免疫浸润分析显示,两组患者的巨噬细胞和单核细胞存在差异。与预后相关的基因主要分布在成纤维细胞、巨噬细胞和 2 型导管中。细胞通讯分析结果显示,癌相关成纤维细胞(CAF)与2型导管细胞之间存在强烈的通讯,胶原形成是主要的相互作用途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The crucial prognostic signaling pathways of pancreatic ductal adenocarcinoma were identified by single-cell and bulk RNA sequencing data.

The crucial prognostic signaling pathways of pancreatic ductal adenocarcinoma were identified by single-cell and bulk RNA sequencing data.

Pancreatic ductal adenocarcinoma (PDAC) is a malignant tumor with poor prognosis and high mortality. Although a large number of studies have explored its potential prognostic markers using traditional RNA sequencing (RNA-Seq) data, they have not achieved good prediction effect. In order to explore the possible prognostic signaling pathways leading to the difference in prognosis, we identified differentially expressed genes from one scRNA-seq cohort and four GEO cohorts, respectively. Then Cox and Lasso regression analysis showed that 12 genes were independent prognostic factors for PDAC. AUC and calibration curve analysis showed that the prognostic model had good discrimination and calibration. Compared with the low-risk group, the high-risk group had a higher proportion of gene mutations than the low-risk group. Immune infiltration analysis revealed differences in macrophages and monocytes between the two groups. Prognosis related genes were mainly distributed in fibroblasts, macrophages and type 2 ducts. The results of cell communication analysis showed that there was a strong communication between cancer-associated fibroblasts (CAF) and type 2 ductal cells, and collagen formation was the main interaction pathway.

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来源期刊
Human Genetics
Human Genetics 生物-遗传学
CiteScore
10.80
自引率
3.80%
发文量
94
审稿时长
1 months
期刊介绍: Human Genetics is a monthly journal publishing original and timely articles on all aspects of human genetics. The Journal particularly welcomes articles in the areas of Behavioral genetics, Bioinformatics, Cancer genetics and genomics, Cytogenetics, Developmental genetics, Disease association studies, Dysmorphology, ELSI (ethical, legal and social issues), Evolutionary genetics, Gene expression, Gene structure and organization, Genetics of complex diseases and epistatic interactions, Genetic epidemiology, Genome biology, Genome structure and organization, Genotype-phenotype relationships, Human Genomics, Immunogenetics and genomics, Linkage analysis and genetic mapping, Methods in Statistical Genetics, Molecular diagnostics, Mutation detection and analysis, Neurogenetics, Physical mapping and Population Genetics. Articles reporting animal models relevant to human biology or disease are also welcome. Preference will be given to those articles which address clinically relevant questions or which provide new insights into human biology. Unless reporting entirely novel and unusual aspects of a topic, clinical case reports, cytogenetic case reports, papers on descriptive population genetics, articles dealing with the frequency of polymorphisms or additional mutations within genes in which numerous lesions have already been described, and papers that report meta-analyses of previously published datasets will normally not be accepted. The Journal typically will not consider for publication manuscripts that report merely the isolation, map position, structure, and tissue expression profile of a gene of unknown function unless the gene is of particular interest or is a candidate gene involved in a human trait or disorder.
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