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Ogino, S. et al.

Shuji Ogino, Katsuhiko Nosho, Yoshifumi Baba, Shoko Kure, Kaori Shima, Natsumi Irahara, Saori Toyoda, Li Chen, Gregory J. Kirkner, Brian M. Wolpin, Andrew T. Chan, Edward L. Giovannucci, Charles S. Fuchs,

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, beta-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 P=0.30). 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 HR=0.60; 95% CI, 0.41-0.87; P=0.0078). Notably, the prognostic effect of obesity (body mass index, BMI> or =30 kg/m2) significantly differed by STMN1 (P(interaction)=0.005). Obesity was associated with high cancer-specific mortality among STMN1-positive patients (adjusted HR=2.36; 95% CI, 1.18-4.69), whereas obesity was not associated with high mortality among STMN1-negative patients (adjusted HR=0.51; 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.[1]

References

A cohort study of STMN1 expression in colorectal cancer: body mass index and prognosis. Ogino, S., Nosho, K., Baba, Y., Kure, S., Shima, K., Irahara, N., Toyoda, S., Chen, L., Kirkner, G.J., Wolpin, B.M., Chan, A.T., Giovannucci, E.L., Fuchs, C.S. Am. J. Gastroenterol. (2009) [Pubmed]

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