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Aliyarov Yusif Rauf

National Centre of Oncology, Azerbaijan

Presentation Title:

The role of KRAS and BRAF gene mutations as predictive markers of radioresistance in patients with locally advanced rectal cancer undergoing neoadjuvant radiochemotherapy

Abstract

Aim: This study aimed to investigate the potential role of mutations in the KRAS and BRAF genes as predictive markers of radioresistance in patients with locally advanced rectal cancer undergoing neoadjuvant radiochemotherapy.

Introduction: Rectal cancer is a significant health concern, and neoadjuvant radiochemotherapy has become a standard treatment approach for patients with locally advanced disease. However, the response to this treatment modality varies among individuals. The identification of predictive markers for treatment response is crucial to optimize therapeutic strategies and improve patient outcomes. Mutations in the KRAS and BRAF genes have been implicated in tumor progression and response to therapy in various cancer types. In this study, we aimed to explore the association between KRAS and BRAF mutations and radioresistance in patients with local advanced rectal cancer undergoing neoadjuvant radiochemotherapy.

Material and methods: A total of 65 patients diagnosed with rectal cancer were enrolled in this study, comprising 31 women and 34 men, with a mean age of 54 years. All patients underwent a prolonged course of neoadjuvant radiochemotherapy. The patients were categorized into three groups based on their response to treatment: the first group with a weak response (16 patients, 24.6%), the second group with a moderate response (34 patients, 52.3%), and the third group with a complete clinical response (15 patients, 23.1%). DNA extraction was performed from formalin-fixed, paraffin-embedded tissues using the Qiagen QIAamp DNA FFPE-kit. Mutation analysis was conducted using the KRAS/BRAF Mutation Analysis Kit for real-time PCR (ENDOGEN) and the CFX96 real-time PCR apparatus (BIORAD USA). Statistical analysis was carried out using IBM SPSS Statistica 20 software.

Results: The analysis of KRAS mutations revealed their presence in 17 patients (26.2%). Among the clinical response groups, the distribution of KRAS mutations was as follows: 6 patients (37.5%) in the first group, 8 patients (23.5%) in the second group, and 3 patients (20%) in the third group (p<0.5). BRAF mutations were detected in 9 patients (13.9%), with 7 patients (43.8%) in the first group, no BRAF mutation in the second group, and 2 patients (13.3%) in the third group (p<0.05). Additionally, five patients had double mutations, with 4 patients in the first group and 1 patient in the third group.

Сonclusion: Our study provides valuable insights into the predictive value of KRAS and BRAF gene mutations for the response to neoadjuvant radiochemotherapy in patients with rectal cancer. The presence of KRAS mutations was associated with a weaker treatment response, while BRAF mutations were predominantly detected in patients with a weak response. These findings underscore the importance of considering KRAS and BRAF mutations  when tailoring treatment strategies for patients with rectal cancer undergoing neoadjuvant radiochemotherapy. Key words: rectal cancer, KRAS, BRAF, neoadjuvant radiochemotherapy

Biography

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