Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

• Main Authors: Justyna Gil, Paweł Karpiński, Maria M. Sąsiadek
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: International Journal of Molecular Sciences
• Subjects: autophagy; gene expression; colorectal cancer
• Online Access: https://www.mdpi.com/1422-0067/21/19/7101

The role of autophagy in colorectal cancer (CRC) pathogenesis appears to be crucial. Autophagy acts both as a tumor suppressor, by removing redundant cellular material, and a tumor-promoting factor, by providing access to components necessary for growth, metabolism, and proliferation. To date, little is known about the expression of genes that play a basal role in the autophagy in CRC. In this study, we aimed to compare the expression levels of 46 genes involved in the autophagy pathway between tumor-adjacent and tumor tissue, employing large RNA sequencing (RNA-seq) and microarray datasets. Additionally, we verified our results using data on 38 CRC cell lines. Gene set enrichment analysis revealed a significant deregulation of autophagy-related gene sets in CRC. The unsupervised clustering of tumors using the mRNA levels of autophagy-related genes revealed the existence of two major clusters: microsatellite instability (MSI)-enriched and -depleted. In cluster 1 (MSI-depleted), <i>ATG9B</i> and <i>LAMP1</i> genes were the most prominently expressed, whereas cluster 2 (MSI-enriched) was characterized by <i>DRAM1</i> upregulation. CRC cell lines were also clustered according to MSI-enriched/-depleted subgroups. The moderate deregulation of autophagy-related genes in cancer tissue, as compared to adjacent tissue, suggests a prominent field cancerization or early disruption of autophagy. Genes differentiating these clusters are promising candidates for CRC targeting therapy worthy of further investigation.