c-peptide and Esophageal-Neoplasms

Insulin-resistance and hyperinsulinemia could have a role in the growing incidence of esophageal adenocarcinoma (EAC) and its pre-cancerous lesion Barrett's Esophagus (BE). HER2 activation has also a pivotal role in EAC carcinogenesis but no data correlate these two phenomena in this disease context.. To investigate the role of hyperinsulinemia in BE-dysplasia-adenocarcinoma sequence and the possible relationship between insulin-mediated and HER2 signaling in EAC development.. Serum insulin, C-peptide, IGF1, glucagon, IL-6, TNF-alpha, leptin, adiponectin and Insulin-Resistance-index were analyzed in 19 patients with gastro-esophageal reflux disease, 51 with BE, 24 with dysplastic-BE and 14 with EAC. Insulin/IGF1/HER2 pathways were analyzed in esophageal biopsies using Luminex. Insulin-Resistance-index, insulin and C-peptide levels increased along with disease progression (p=0.019, p=0.002, p<0.0001, respectively) and correlated with HER2 expression and with downstream mediators phospho-Akt and phospho-mTOR in esophageal tissue. In vitro, insulin was also able to induce cell proliferation through HER2 activation.. Our data pinpoint a possible role of hyperinsulinemia in the Barrett's Esophagus metaplasia-dysplasia-adenocarcinoma sequence through HER2 activation in esophageal epithelial cells.

Topics: Adenocarcinoma; Adult; Aged; Barrett Esophagus; C-Peptide; Disease Progression; Esophageal Neoplasms; Esophagus; Female; Gastroesophageal Reflux; Humans; Immunohistochemistry; Insulin; Insulin Resistance; Interleukin-6; Italy; Male; Middle Aged; Receptor, ErbB-2; Signal Transduction; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

Adipocytokines are adipocyte-secreted hormones associated with some malignancies. It has been reported that the impaired response of adipocytokines to body weight loss may play a role in the pathogenesis of cancer-induced cachexia. We investigated the association between adipocytokines with squamous cell carcinoma of the esophagus (SCCE).. The levels of body mass index (BMI) and adiponectin, leptin, resistin, visfatin and C-peptide in the blood at diagnosis were measured in 117 SCCE patients and 117 age- and sex-matched controls. Logistic regression models were employed to estimate odds ratio. One-way analysis was performed to examine the prevalence of variables between two or more groups. A non-parametric Spearman correlation test was conducted to examine the associations between BMI and other variables.. Adiponectin and BMI levels were significantly lower, and resistin level was significantly higher in the patients on multivariate analysis (P = 0.01, <0.01 and <0.01 respectively). BMI gradually decreased with stage progression, and resistin level gradually increased with stage progression (P < 0.01 for both). The inverse correlation between BMI and adiponectin was comparatively strong in the controls, but was weak in the patients. Leptin showed comparatively strong correlation with BMI in the controls, but was weakly correlated in the patients. The correlation between BMI and resistin or C-peptide was demonstrated weakly only in the controls, and visfatin did not correlate with BMI.. Resistin may be a biomarker for the progression of SCCE. In addition, the impaired responses to body weight loss of adiponectin and leptin in the patients with SCCE were suggested.

Topics: Adipokines; Adiponectin; Aged; Analysis of Variance; Biomarkers, Tumor; Body Mass Index; C-Peptide; Cachexia; Carcinoma, Squamous Cell; Case-Control Studies; Disease Progression; Esophageal Neoplasms; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Neoplasm Staging; Nicotinamide Phosphoribosyltransferase; Odds Ratio; Resistin