A cohort study of STMN1 expression in colorectal cancer: body mass index and prognosis.
OBJECTIVE
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.
Ogino
Shuji
S
Department 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
Nosho
Katsuhiko
K
Baba
Yoshifumi
Y
Kure
Shoko
S
Shima
Kaori
K
Irahara
Natsumi
N
Toyoda
Saori
S
Chen
Li
L
Kirkner
Gregory J
GJ
Wolpin
Brian M
BM
Chan
Andrew T
AT
Giovannucci
Edward L
EL
Fuchs
Charles S
CS
D000368:Aged; D015992:Body Mass Index; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D050777:Stathmin / Q000096:biosynthesis*; D015996:Survival Rate
C493995:STMN1 protein, human; D050777:Stathmin