KRAS Mutations in Colorectal Cancer: Relationship With Clinicopathological Characteristics and Impact on Clinical Outcomes in Saudi Arabia

Abstract

Background Few studies have addressed the prevalence and prognostic impacts of KRAS mutations in Saudi patients with colorectal cancer (CRC). The present study aimed to address the prevalence of KRAS mutations and evaluate their impact on clinical outcomes (if any) among Saudi patients. Methods This retrospective cohort study was conducted at King Saud University Medical Centre (KSUMC), Saudi Arabia. All medical records of biopsy-proven CRC patients between 2015 and 2021 were reviewed. Statistical analysis was carried out to address the associations between KRAS mutations and the clinicopathological patients’ variables and survival. Results KRAS mutations were found in 97/194 (50%) CRC patients. In comparison to wild type KRAS tumors, KRAS- mutated ones had shown a trend toward right-sided tumors (30% and 4.3% vs 16% and 1.1%, p-value = 0.032, respectively) and peritoneal metastases (34% vs 19%, p-value = 0.014). Older age at diagnosis, gender, tumor grade, microsatellite instability (MSI), tumor stage (T), and the presence of distant metastasis were independent prognostic factors for poor overall survival (OS). There was no significant association between KRAS mutations and the hazard of mortality (HR: 0.653, 95% CI 0.873-1.134, p = 0.131). For progression-free survival (PFS), older age at presentation, MSI, tumor nodal stage (N), the presence of liver and lung metastasis, and recurrence were poor prognostic factors for PFS. There was no significant relation between KRAS mutations and PFS (HR ratio: 0.756, 95% CI 0.229-2.497, p = 0.646). Conclusions The prevalence of KRAS mutations in CRC patients was similar to that observed in previous studies of Saudi patients. KRAS mutations showed a trend toward right-sided tumors and peritoneal metastases. Survival was significantly related to different clinicopathologic variables of the study cohort but was not affected by the KRAS mutational status.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…The frequency of KRAS mutations (exon 2 and exon 3) in our cohort reached 61.88%. This was much higher than what was reported in the Asia-Pacific (37-52%) and Western populations (32-49%) [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Nevertheless, our data is in line with a previous study in Indonesia, showing that KRAS mutation was found in 71.8% of serrated adenocarcinoma (SA), which is intriguingly higher than the generally reported incidence of 40% [39][40][41].…”

“…Consequently, our high co-mutation rate in the Indonesian population can shed new light that warrants further investigation. This study and others have shown that KRAS mutation was more frequent in right sided CRC [37,54,55]. The predilection of KRAS mutations for the right side of the colon may be influenced by the fact that the right and left side of the colon have different biology and histopathology in their respective embryological origins [37,56,57].…”

“…This study and others have shown that KRAS mutation was more frequent in right sided CRC [37, 54, 55]. The predilection of KRAS mutations for the right side of the colon may be influenced by the fact that the right and left side of the colon have different biology and histopathology in their respective embryological origins [37, 56, 57]. Right-sided CRC often has flat histopathology and a DNA mismatch repair pathway deficiency [58].…”

Systematic analysis of cancer‐specific synthetic lethal interactions provides insight into personalized anticancer therapy

“…Interestingly, among these genes, the highest number of genetic interactions were found for KRAS (Fig. 3E), which had important roles in the occurrence and development of diverse cancers [37,38]. These findings confirmed a crucial role and great potential application of KRAS in synthetic lethality.…”

Impact of KRAS Mutation on Survival Outcome of Patients With Metastatic Colorectal Cancer in Jordan

“…However, other studies have reported conflicting results with our study and have found no significant difference in survival outcomes between mutant and wild type in mCRC. For example, a study published in 2022 by Alghamdi et al found that KRAS mutational status did not significantly affect OS or progressionfree survival in patients with mCRC [15]. This inconsistency in the literature may be due to differences in study design, patient populations, and treatment regimens.…”