A Cohort study of STMN1 expression in colorectal cancer: Body mass index and prognosis

OBJECTIVES: STMN1 (stathmin or oncoprotein-18) destabilizes microtubules and reorganizes cytoskeleton, and functions in cell cycle progression and cell migration. STMN1 activity is influenced by p53, p27, and the PI3K/AKT pathway. However, its prognostic significance in colon cancer is uncertain.METHODS: Utilizing 546 colorectal cancers (stage I-IV) from two independent prospective cohort studies (the Nurses Health Study and Health Professionals Follow-up Study), STMN1 expression was detected in 297 (54%) tumors by immunohistochemistry. Cox proportional hazard models computed hazard ratios (HRs) of mortality, adjusted for clinical and tumoral features, including microsatellite instability (MSI), CpG island methylation phenotype (CIMP), LINE-1 hypomethylation, KRAS, BRAF, PIK3CA, p53, p21, p27, cyclin D1, Β-catenin, fatty acid synthase, FASN, and COX-2.RESULTS:Five-year colorectal cancer-specific survival was 78% in STMN1-positive patients and 76% in STMN1-negative patients (log-rank P0.30). STMN1-positivity was not significantly associated with cancer-specific survival in univariate analysis with HR of 0.82 (95% confidence interval (CI), 0.59-1.14), which became significant in multivariate analysis (adjusted HR0.60; 95% CI, 0.41-0.87; P0.0078). Notably, the prognostic effect of obesity (body mass index, BMI3≥0 kg/m²) significantly differed by STMN1 (P_interaction 0.005). Obesity was associated with high cancer-specific mortality among STMN1-positive patients (adjusted HR2.36; 95% CI, 1.18-4.69), whereas obesity was not associated with high mortality among STMN1-negative patients (adjusted HR0.51; 95% CI, 0.24-1.07).CONCLUSIONS:STMN1 overexpression in colorectal cancer is independently associated with improved survival. The adverse prognostic effect of obesity was limited to patients with STMN1-positive tumors. Our findings suggest the presence of a tumor (STMN1)-host (BMI) interaction that potentially determines clinical outcome.