Identification and Characterization of the Copy Number Dosage-Sensitive Genes in Colorectal Cancer

Abstract

Dosage effect is one of the common mechanisms of somatic copy number alteration in the development of colorectal cancer, yet the roles of dosage-sensitive genes (DSGs) in colorectal cancer (CRC) remain to be characterized more deeply. In this study, we developed a five-step pipeline to identify DSGs and analyzed their characterization in CRC. Results showed that our pipeline performed better than existing methods, and the result was significantly overlapped between solid tumor and cell line. We also found that the top five DSGs (PSMF1, RAF1, PTPRA, MKRN2, and ELP3) were associated with the progression of CRC. By analyzing the characterization, DSGs were enriched in driver genes and they drove sub-pathways of CRC. In addition, immune-related DSGs are associated with CRC progression. Our results also showed that the CRC samples affected by high microsatellites have fewer DSGs, but a higher overlap with DSGs in microsatellite low instability and microsatellite stable samples. In addition, we applied DSGs to identify potential drug targets, with the results showing that 22 amplified DSGs were more sensitive to four drugs. In conclusion, DSGs play an important role in CRC, and our pipeline is effective to identify them.

Keywords

• colorectal cancer
• copy number
• dosage sensitive
• driver gene
• drug target
• cancer immunity