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Am J Gastroenterol. 2009 Aug;104(8):2047-56. doi: 10.1038/ajg.2009.281. Epub 2009 Jun 9.

A cohort study of STMN1 expression in colorectal cancer: body mass index and prognosis.

Author information

  • 1Department of Medical Oncology, Center for Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Brigham and Women's Hospital and Harvard Medical School, 44 Binney St, Room JF-215C, Boston, Massachusetts 02115, USA. shuji_ogino@dfci.harvard.edu

Abstract

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.

PMID:
19513025
[PubMed - indexed for MEDLINE]
PMCID:
PMC2866652
Free PMC Article

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