The Expression Of Leptin, Ghrelin And Their Receptors In Colorectal Cancer And Their Prognostic Values

ObjectiveColorectal cancer (CRC) is the third common type of malignant tumors In China, which is also the5th leading cause of cancer-related mortality. Obesity, which is becoming a social problem, is known as a risk factor of CRC.Resently a research found that obesity is an independent prognositic factor for CRC. As Ghrelin and Leptin are obesity-related hormones, this experiment aims to illustrate the relationship between these hormones and the characteristic of CRC patients and determine whether can be used as prognostic markers.Methods1. The postoperative tumor tissue samples, paratumor tissue samples and their preoperative serum specimens from240patients with sporadic CRC in our hospital were collected from July2003to May2010, all the tumor tissues are conformed as malignant and stage Ⅱ and Ⅲ of TNM staging system, the median time of follow-up is48months and all the living patients have been followed up more than2years till now.2. Expression of Leptin, Leptin receptor and Ghrelin receptor in tumor tissues are detected by immunohistochemical staining; Serum specimens are detected by ELISA.3. The clinical-pathological characteristics and follow-up information were analyzed with statistic analysis to identify the prognostic values of Ghrelin、 leptin and their receptor in CRC.Results1.56.2%CRC patients showed positive expression of GHSR in tumor tissues, and61.5%in paratumoural tissues, the expression had no significant difference between these two groups (p=0.392).35.6%CRC patients showed positive expression of Leptin in tumor tissues, and4.3%in paratumoural tissues. The expression had significant difference between these two groups (P=5.26×10-7).2.5%CRC patients showed positive expression of OBR in tumor tissues.2. Expression of GHSR correlated well with differentiation of tumor (P=0.036); the expression of GHSR is an independent prognostic factor in CRC tumor, the disease-free survival (DFS) is significantly longer in GHSR positive patients than negative patients(median time is55.4months vs35.9months, P=0.007); The leptin expression correlates negatively well with DFS, but after multivariate Cox regression analysis this correlation disappear. Detection of GHSR and downregulation/negative expression of Leptin in CRC is also an independent favorable prognostic factor(P=0.05), its specificity for good outcome is higher than only the GHSR detection(76.1%vs71%), but there is no statistical significance and after combination the sensitivity is much lower(P=0.004).The serum Leptin level correlates well with both overall survival (OS) and DFS, but no statistical significance. Serum Ghrelin level has no relationship with prognosis.Conclusion1. The expression of GHSR is an independent prognostic factor that affects the DFS of CRC patients;2. Detection of upregulation of GHSR combining with downregulation of leptin is also an independent prognostic factor of CRC patients, but it is no better than the single detection of GHSR expression;3. High level of serum Leptin level is a good factor for CRC prognosis, which might be used as a excellent prognostic factor.