Associations between colorectal cancer (CRC) survival and mutations in
mediator of MAPK/ERK (RAS-BRAF-MEK-ERK) and PIK3CA/AKT signaling
pathways have been reported. The objective of this study was to evaluate
the influence of mutations in the EGFR pathway (KRAS, NRAS, BRAF and
PIK3CA) on overall survival in CRC. We conducted a retrospective
observational cohort study comprising 194 paraffin tumor samples from
patients diagnosed with colorectal cancer were analyzed for KRAS codons
12, 13 and 61, NRAS codons 12, 13 and 61, BRAF and PIK3CA exons 9 and 20
gene mutations. Multivariate analysis confirmed that patients with ECOG
of 0 presented lower risk of death (HR = 0.17, CI95%, 0.10 -0.31, p =
1656.10-9) compared to a higher ECOG (Table 4). The only independent
genetic association was between PIK3CA20 mutation (H1047Y; rs121913281)
and higher risk of death (HR = 8.93, CI95%, 1.20-66.57, p = 0.03268).
No association was found between the rest of the mutations analyzed and
overall survival. To explore the effect of mutations in patients with
different degrees of ECOG, a stratified analysis was performed.
Multivariate analysis in patients with ECOG 0 group confirmed the
association between mutations of PIK3CA and an increased risk of death:
E545K (HR = 5.49, CI95%, 1.28-23.51, p = 0.021720) and H1047Y (HR =
53.49; %, 4.63-617.40, p = 0.001429). In conclusion, our results show
PIK3CA gene mutations may predict the overall survival of CRC patients,
positioning PIK3CA as a potential biomarker for survival in CRC.