Published online Aug 28, 2023. doi: 10.3748/wjg.v29.i32.4883
Peer-review started: May 20, 2023
First decision: June 22, 2023
Revised: July 6, 2023
Accepted: July 31, 2023
Article in press: July 31, 2023
Published online: August 28, 2023
Processing time: 96 Days and 15.3 Hours
Abnormal activation of Kirsten rat sarcoma viral oncogene homolog (KRAS), a well-known oncogene, triggers uncontrolled tumor cell proliferation. Approximately 40% of colorectal cancer (CRC) are linked to KRAS mutations. CRC -related point mutations in KRAS occur at different codon locations. KRAS codon 12 or 13 mutations are detected in a majority of CRC patients, whereas mutations in codon 61 or 146 have been reported only in a minority.
KRAS mutations are associated with poor CRC prognosis, especially KRAS codon 12 mutation, which is associated with metastasis and poorer survival. However, the clinicopathological characteristics and prognosis of KRAS codon 13 mutation in CRC remain controversial.
This study aimed to evaluate the clinicopathological characteristics and prognostic value of codon-specific KRAS mutations, especially in codon 13.
This retrospective, single-center, observational cohort study included patients who underwent surgery for stage I-III CRC. The relationships between clinicopathological characteristics and individual codon-specific KRAS mutations were analyzed. By using the Cox proportional hazards regression model, survival analysis were performed to identify codon-specific KRAS mutations as recurrence-related factors.
Both KARS codons 12 and 13 mutations showed a tendency to be associated with clinical characteristics, but only codon 12 was associated with pathological features. KRAS codon 13 mutation showed no associations, whereas codon 12 was associated with a lower 5-year recurrence-free survival rate. In multivariable analysis, only codon 12 (HR: 1.399; 95% confidence interval: 1.034-1.894; P = 0.030) among KRAS mutations was an independent risk factor for recurrence. This may influence many oncologists to consult with patients on their prognosis after surgery.
KRAS codon 12 mutation was significantly associated with pathological features closely related to cancer recurrence and had a poor prognostic impact in patients with microsatellite stable tumors, or those located in the colon but not in the rectum. On the other hand, KRAS codon 13 mutation is irrelevant to pathological features and recurrence, which consider less likely to serve as a prognostic factor for CRC.
Focusing on the biological effects of codon-specific KRAS mutations, KRAS codon 13 mutation is less pathogenic and recurrent, Based on a large-scale cohort of patients with stage I-III CRC. This study’s results may influence not only the prognosis but also the management of CRC patients individually. Therefore, the therapeutic usage and needs of codon-specific KRAS mutation in CRC should be considered in future studies.