Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

Abstract

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), ATG9B and LAMP1 genes were the most prominently expressed, whereas cluster 2 (MSI-enriched) was characterized by DRAM1 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.

Fusobacterium nucleatum and its metabolite hydrogen sulfide alter gut microbiota composition and autophagy process and promote colorectal cancer progression

“…Deficiency of ATG7 in tumor cells but not in normal cells led to p53-mediated cell cycle arrest, suggesting a pro-oncogenic role for this gene ( 50 ). In CRC tumors with high microsatellite instability, DRAM1 shows high expression ( 51 ) and it plays a positive regulatory role in the autophagy process ( 52 ). In addition, DRAM1 expression decreased in human colon cancer cells treated with anti-PD-1 nivolumab, suggesting that DRAM1 is a pro-cancer-associated autophagy gene ( 53 ), which is consistent with the results of this study.…”

Moxidectin induces lethal autophagy arrest via CFTR

“…In recent years, considerable attention has been paid to the role of autophagy in cancer therapy, which can improve anticancer therapy and play an integral role in tumor maintenance [19,20] . In most cases, the treatment of cancer by autophagy is accompanied with an increased autophagic ux.…”

Construction and Validation of an Autophagy-Related Prognostic Model for Osteosarcoma Patients

“…222 ARGs were curated based on previous studies [29][30][31]. Univariate cox regression analysis was conducted to extract potential prognostic ARGs with a cutoff of P < 0.05 using the "survival" R package.…”