Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

Area of Science:

• Oncology
• Molecular Biology
• Cellular Biology

Background:

• Autophagy plays a dual role in colorectal cancer (CRC) pathogenesis, acting as both a tumor suppressor and promoter.
• The expression patterns of basal autophagy genes in CRC remain largely unexplored.

Purpose of the Study:

• To compare the expression levels of 46 autophagy-related genes in tumor-adjacent versus tumor tissues in CRC.
• To investigate the correlation between autophagy gene expression and microsatellite instability (MSI) status in CRC.
• To identify potential therapeutic targets within the autophagy pathway for CRC treatment.

Main Methods:

• Utilized large-scale RNA sequencing (RNA-seq) and microarray datasets to analyze gene expression.
• Performed gene set enrichment analysis to identify deregulated autophagy pathways.
• Employed unsupervised clustering to group CRC tumors and cell lines based on autophagy gene expression and MSI status.

Main Results:

• Significant deregulation of autophagy-related gene sets was observed in CRC.
• Two distinct tumor clusters emerged based on autophagy gene expression: MSI-depleted (enriched for ATG9B and LAMP1) and MSI-enriched (upregulated DRAM1).
• CRC cell lines also segregated into MSI-enriched and -depleted subgroups based on autophagy gene expression.

Conclusions:

• The findings suggest a field cancerization effect or early disruption of autophagy in CRC.
• Specific autophagy genes, such as ATG9B, LAMP1, and DRAM1, are differentially expressed and associated with MSI status in CRC.
• These identified genes represent promising candidates for targeted CRC therapies warranting further investigation.