Functional Proteomic Profiling Analysis in Four Major Types of Gastrointestinal Cancers

Abstract

Gastrointestinal (GI) cancer accounts for one in four cancer cases and one in three cancer-related deaths globally. A deeper understanding of cancer development mechanisms can be applied to cancer medicine. Comprehensive sequencing applications have revealed the genomic landscapes of the common types of human cancer, and proteomics technology has identified protein targets and signalling pathways related to cancer growth and progression. This study aimed to explore the functional proteomic profiles of four major types of GI tract cancer based on The Cancer Proteome Atlas (TCPA). We provided an overview of functional proteomic heterogeneity by performing several approaches, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), t-stochastic neighbour embedding (t-SNE) analysis, and hierarchical clustering analysis in oesophageal carcinoma (ESCA), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ) tumours, to gain a system-wide understanding of the four types of GI cancer. The feature selection approach, mutual information feature selection (MIFS) method, was conducted to screen candidate protein signature subsets to better distinguish different cancer types. The potential clinical implications of candidate proteins in terms of tumour progression and prognosis were also evaluated based on TCPA and The Cancer Genome Atlas (TCGA) databases. The results suggested that functional proteomic profiling can identify different patterns among the four types of GI cancers and provide candidate proteins for clinical diagnosis and prognosis evaluation. We also highlighted the application of feature selection approaches in high-dimensional biological data analysis. Overall, this study could improve the understanding of the complexity of cancer phenotypes and genotypes and thus be applied to cancer medicine.