KRAS Gene Mutation Associated with Grade of Tumor Budding and Peripheral Immunoinflammatory Indices in Patients with Colorectal Cancer.

Background: The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC.

Methods: Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed.

Results: 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287-3.016, p=0.002), and high SII level (≥807.81 vs <807.81, OR: 1.915, 95% CI: 1.120-3.272, p=0.018) were independently associated with KRAS mutation.

Conclusion: Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.