AI Article Synopsis
- Despite the presence of KRAS mutations in colorectal cancer (CRC) patients, no effective treatments specifically targeting these mutations have been developed yet.
- The study analyzed gene expression differences between CRC patients with wild-type KRAS and those with mutations in codon 12, identifying at least 11 candidate molecules with significant expression changes.
- Three particular genes (BMP4, PHLDA1, and GJB5) showed increased expression in cell lines with KRAS G12 mutations, suggesting potential pathways for developing new treatments for KRAS-driven CRC.
Article Abstract
Despite the frequent detection of KRAS driver mutations in patients with colorectal cancer (CRC), no effective treatments that target mutant KRAS proteins have been introduced into clinical practice. In this study, we identified potential effector molecules, based on differences in gene expression between CRC patients carrying wild-type KRAS (n = 390) and those carrying KRAS mutations in codon 12 (n = 240). CRC patients with wild-type KRAS harboring mutations in HRAS, NRAS, PIK3CA, PIK3CD, PIK3CG, RALGDS, BRAF, or ARAF were excluded from the analysis. At least 11 promising candidate molecules showed greater than two-fold change between the KRAS G12 mutant and wild-type and had a Benjamini-Hochberg-adjusted P value of less than 1E-08, evidence of significantly differential expression between these two groups. Among these 11 genes examined in cell lines transfected with KRAS G12 mutants, BMP4, PHLDA1, and GJB5 showed significantly higher expression level in KRAS G12A, G12D, and G12V transfected cells than in the wild-type transfected cells. We expect that this study will lead to the development of novel treatments that target signaling molecules functioning with KRAS G12-driven CRC.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342352 | PMC |
| http://dx.doi.org/10.1007/s11010-021-04172-8 | DOI Listing |
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