Is There Any Correlation Among MKK4 ('Mitogen-activated protein kinase kinase 4') Expression, Clinicopathological Features & KRAS / NRAS mutation in Colorectal Cancer.

Background We aimed to evaluate the correlation between MKK4 expression and clinicopathological features, KRAS/NRAS mutation in colorectal cancer. Methods MKK4 expression was assessed by immunoreactivity score (IRS). Staining intensity(SI) and percentage of positively stained cells (PP) were used for IRS (IRS = SIxPP). Cutoffs were explored with ROC analysis. Patients were grouped as WIR ('weak immunoreactive'; IRS:0-2) and SIR ('strong immunoreactive'; IRS: >3). Results We enrolled 95 patients. 63.2% had metastasis. Median follow-up was 31.4 months. KRAS/NRAS mutation rate was 45.2%. Median values for OS, DFS, and PFS were as 31.6, 17.2, and 10.3 months. WIR group had longer OS (p= 0.03). Recurrence rate was 36.8%. Median DFS was longer for recurrent patients in WIR group (p= 0.055). KRAS or NRAS wild-type patients and those with left-sided tumors in WIR group had longer OS (p= 0.029,p= 0.024,p= 0.03). There was no PFS difference (p: 0.15). In correlation analysis, there was a negative correlation between MKK4 expression and KRAS mutation, NRAS mutation, OS, PFS, DFS (r: -0,06;r: -0,02;r: -0,10;r: -0,06;r: -0,34). Only the correlation for MKK4 expression and DFS was significant (p= 0.04). Conclusion MKK4 expression inversely correlates with survival outcomes. Patients with KRAS/NRAS wild-type, left-sided tumors with WIR had longer OS.