Department of Biomedical Sciences, School of Health Sciences, University of Zambia, Lusaka, Zambia.
Department of Pathology and Microbiology, School of Medicine, University of Zambia, Lusaka, Zambia.
PLoS One. 2021 Sep 10;16(9):e0257084. doi: 10.1371/journal.pone.0257084. eCollection 2021.
Pancreatic cancer remains a significant public health problem with an ever-rising incidence of disease. Cancers of the pancreas are characterised by various molecular aberrations, including changes in the proteomics and genomics landscape of the tumour cells. Therefore, there is a need to identify the proteomic landscape of pancreatic cancer and the specific genomic and molecular alterations associated with disease subtypes. Here, we carry out an integrative bioinformatics analysis of The Cancer Genome Atlas dataset, including proteomics and whole-exome sequencing data collected from pancreatic cancer patients. We apply unsupervised clustering on the proteomics dataset to reveal the two distinct subtypes of pancreatic cancer. Using functional and pathway analysis based on the proteomics data, we demonstrate the different molecular processes and signalling aberrations of the pancreatic cancer subtypes. In addition, we explore the clinical characteristics of these subtypes to show differences in disease outcome. Using datasets of mutations and copy number alterations, we show that various signalling pathways previously associated with pancreatic cancer are altered among both subtypes of pancreatic tumours, including the Wnt pathway, Notch pathway and PI3K-mTOR pathways. Altogether, we reveal the proteogenomic landscape of pancreatic cancer subtypes and the altered molecular processes that can be leveraged to devise more effective treatments.
胰腺癌仍然是一个严重的公共卫生问题，其发病率不断上升。胰腺肿瘤的特征是各种分子异常，包括肿瘤细胞的蛋白质组学和基因组学景观的改变。因此，有必要确定胰腺癌的蛋白质组学景观以及与疾病亚型相关的特定基因组和分子改变。在这里，我们对包括来自胰腺癌患者的蛋白质组学和全外显子测序数据在内的癌症基因组图谱数据集进行综合生物信息学分析。我们对蛋白质组学数据集进行无监督聚类，以揭示两种不同的胰腺癌亚型。使用基于蛋白质组学数据的功能和途径分析，我们证明了胰腺癌亚型的不同分子过程和信号异常。此外，我们还探讨了这些亚型的临床特征，以显示疾病结果的差异。使用突变和拷贝数改变数据集，我们表明先前与胰腺癌相关的各种信号通路在两种胰腺癌亚型中均发生改变，包括 Wnt 通路、Notch 通路和 PI3K-mTOR 通路。总之，我们揭示了胰腺癌亚型的蛋白质基因组景观以及可以利用的改变分子过程，以设计更有效的治疗方法。
