Analysis of Hotspot <i>PIK3CA</i> Mutations (E542K and E545K) in Iranian Colorectal Cancer Patients

Abstract

Background: Colorectal cancer (CRC) is the third most common and the second deadliest cancer, causing about 10% of cancer deaths worldwide. Changes in the PIK3CA gene are important for CRC development and treatment response. Objectives: This study aimed to evaluate mutations in the PIK3CA gene, specifically E542K and E545K, linked to CRC in the Iranian population. Methods: This study analyzed 39 CRC tumor samples from Dr. Ganjavian Hospital and Imam Ali Clinic in Dezful. DNA was extracted using the phenol-chloroform method, followed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and sequencing to identify mutations. Results: Thirty-nine patients were examined in this study, comprising 14 women (35.9%) and 25 men (64.1%). The mean age of the participants was 59.2 years, with a standard deviation of 15.9 years. The findings indicated that 46.1% of the patients presented with tumors exceeding 4.5 cm in size, whereas 53.9% had tumors that were 4.5 cm or smaller. Lymphoid metastasis was observed in 55.81% of all patients, with those having tumors larger than 4.5 cm exhibiting a notably higher incidence of this metastasis. The most frequently encountered tumor grades among the participants were grades 1 and 2. Staging was identified as follows: 18.42% were classified as stage 1, 50% as stage 2, and 31.58% as stage 3. No E542K or E545K mutations were detected in any of the 39 CRC patients (0%). Conclusions: This research suggests no correlation between mutations in the PIK3CA gene and the occurrence of CRC within the studied population, but a significant correlation was observed between tumor size > 4.5 cm and lymphoid metastasis (P < 0.001). These findings underscore the importance of population-specific genetic profiling in CRC, even in the absence of expected mutations.