Investigating the association of inflammatory markers with clinical outcomes of patients with KRAS and BRAF V600E-mutated colorectal cancer.

Abstract

200 Background: Patients with colorectal cancer (CRC), particularly those with BRAF and KRAS mutations, often present with high inflammatory markers such as elevated WBC and platelet counts. However, it is unknown whether these inflammatory markers are associated with clinical outcomes of patients with KRAS and BRAF V600E-mutated CRC. In this study, we investigated the potential biomarker role of inflammatory markers in these subgroups of CRC. Methods: We evaluated patients with MSS metastatic CRC (mCRC) at our institution, we included 271 patients with KRAS-mutated and 32 with BRAF V600E–mutated mCRC. Demographic and clinical, laboratory, and molecular data were retrieved by electronic medical records review. Cox proportional hazards regression and Kaplan-Meier survival analyses were performed to assess the association of these factors with overall survival (OS), with statistical significance determined by a p-value threshold of <0.05. Results: A total of 271 patients with KRAS-mutated and 32 with BRAF V600E–mutated MSS mCRC were included. Median age at diagnosis was 62 years overall. Females comprised 53% of BRAF and 47% of KRAS patients. White patients accounted for 94% and 84%, respectively. Colon was the primary site in 88% of BRAF vs 72% of KRAS cases. Abnormal WBC was noted in 31% vs 26%, platelets in 22% vs 30%, neutrophils in 31% vs 29%, and lymphocytes in 25% vs 17%. High WBC counts were associated with inferior survival compared with normal or low counts (median OS 21.7 vs 35.4 and 33.9 mo., log-rank p=0.022), and higher mortality on Cox regression (HR 1.61, 95% CI 1.13–2.29, p=0.008), and this remained significant predictor as a continuous variable. High platelet counts were associated with shorter survival compared with normal or low counts (median OS 24.2 vs 33.7 and 57.6 mo., log-rank p=0.053). Cox regression showed borderline association with increased mortality (HR 1.42, 95% CI 1.0-1.97, p=0.051), the association remained significant when modeled as a continuous variable. High neutrophil counts were associated with shorter overall survival in KRAS cohort as well (median OS 22.5 vs 33.6–35.1 mo., p=0.065). Cox regression confirmed increased mortality risk (HR 1.43, 95% CI 1.04–1.97, p=0.028), and the association remained significant when modeled as a continuous variable. Lastly, when modeled continuously, both platelet—lymphocyte ratio and neutrophil-lymphocyte ratio were significantly associated with OS (p<0.001 each, respectively). Contrarily, in the BRAF V600E–mutated cohort, none of the evaluated inflammatory markers demonstrated a significant association with survival. Conclusions: Inflammatory markers were prognostic for survival in patients with KRAS-mutated MSS mCRC but not BRAF V600E. Elevated WBC, platelet, and neutrophil counts, PLR, and NLR predicted worse outcomes in KRAS, supporting their role as biomarkers in this subgroup.