Leptin, the product of the ob gene, is an adipocyte-derived
neurohormone that regulates body fat storage and feeding behavior. Some studies have suggested that
leptin has
growth-factor-like functions in epithelial cells and its abnormal expression may be involved in
cancer development and progression. We investigated
leptin expression in normal and neoplastic colorectal tissues and its association with clinicopathological features and clinical outcome in colorectal
adenocarcinoma patients.
Leptin expression was evaluated on the tissue microarray of 44 normal colon mucosal tissues, 44
adenomatous polyps, and 437 colorectal
adenocarcinomas by immunohistochemistry. Data were analyzed by chi-square test, one-way analysis of variance (ANOVA), Cox regression hazards model, and log-rank test with Kaplan-Meier curves. Frequency of
leptin expression was dramatically increased from normal colonic mucosa (2/44, 4.5%) to
adenomas (13/44, 29.5%) and
adenocarcinomas (321/437, 73.5%) as neoplastic progression. Interestingly,
leptin expression was correlated with favorable
tumor features in depth of invasion (p = 0.033),
lymph node metastasis (p = 0.019), American Joint Committee on
Cancer (AJCC) and Dukes' stage (p = 0.021 and p = 0.005, respectively), differentiation (p = 0.010), and lymphatic invasion (p = 0.003). In univariate survival analysis, patients with
leptin-positive
adenocarcinoma revealed better overall and disease-free survivals (p = 0.032 and p = 0.004, respectively, log-rank test). In multivariate survival analysis with Cox proportional hazards model,
leptin expression was an independent prognostic marker of disease-free survival (p = 0.009). We conclude that
leptin was gradually expressed during the normal-
adenoma-
adenocarcinoma sequence, suggesting an association in colorectal
carcinogenesis. In addition, high
leptin expression was an
indicator of favorable
tumor features and better survival of
colorectal cancer patients.