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Title:
Ghrelin level in plasma of healhy group and in patients with colorectal cancer
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postprandial ; colorectal cancer ; ghrelin
Abstract:
Colorectal cancer (CRC) is one of the most common tumors in human population. Several risk factors such as epidemiological, intestinal and diet have been identified. Researchers still look for factors that would be able to join these elements in a logical way. One of such integrating factors could be 28-amino acid hormone, discovered in 1999, named “ghrelin”. At present, function of ghrelin is a subject of intensive research. Its wide distribution in the human body indicate a wide spectrum of application. Published results show a possible direct or indirect role of ghrelin in the carcinogenesis of the colorectal and other cancers. However, ghrelin level and/or changes in ghrelin level in CRC patients have not been studied in detail until now. Research hypothesis: Based on published results it is possible that ghrelin could be primary or secondary risk factor of developing colorectal cancer and its level and/or changes in level in blood differ between healthy individuals and patients with colorectal cancer. Aim: The aim of this research was to determine usefulness of ghrelin measure in blood plasma in patients with colorectal cancer through comparison of ghrelin level in male and female group: in fasting state in patients with CRC and healthy group, after ingestion of long chain triglycerides and before and after operation. Plasma ghrelin level was also comp ; ared between subgroups divided in respect of location of CRC, its staging, grading presence or absence of mucinous adenocarcinoma cells. Furthermore, correlation between plasma ghrelin level and selected parameters of nutritional status, carcinoembryonic antigen (CEA) and plasma leptin level were examined in group of patients with colorectal cancer. Material and Methods: 47 patients with CRC (23 male and 22 female; ranging in age from 36 to 85 years with a mean of 68.1 years) treated in the Department of General Surgery and 37 healthy individuals (16 male and 21 female; ranging in age from 22 to 67 years with a mean age of 40.4 years) were included in the study. From patients fulfilling the inclusion and exclusion criteria, the full protocol was carried out in 31 patients. In 16 patients ghrelin level was measured before and on the 7. postoperative day due to technical and methodological problems. The full protocol of the study consisted of preoperative collection of ghrelin fasting blood sample, ingestion of 100 ml long chain triglycerides and blood sampling performed every 60min for 2 housers postprandialy. Additionally, a fasting blood sample was collected on the 7. day postoperatively. Selected parameters, including body mass index, nutritional status, location of tumor, grading, staging, preoperative CEA and leptin level were analyzed in this study. T ; otal ghrelin and leptin level in plasma were analyzed using commercially available RIA. Forty percent, 23%, 17%, 10%, 8% and 2% of the subjects were affected, respectively, by carcinomas of the rectum, sigmoideum, caecum, colon descendens, colon ascendens and transversum. All the patients were operated on. Three (6.4%), 12 (25.5%), 6 (12.8%), 8 (17%) and 13 (27.6%) of the subjects had, respectively, local excision using TEM (Transanal Endoscopic Microsurgery), right hemicolectomy, left hemicolectomy, sigmoidectomy, low anterior and intersphincteric rectum resection. All these patients had a macro- and microscopic radical operation. Colorectal adenocarcinoma was confirmed in all cases in postoperative histopathological examination. Ten percent of the adenocarcinomas were at stage pT1 according to TNM staging system, 17% at stage pT2 , 10% at stage pT3 and 61% at stage pT4. In 26 patients (55,3%) there was no regional lymph nodes invasion detected (pN0). In 10 subjects (21,3%) there was between 1 and 3 positive lymph nodes (pN1) and in 11 (23,4%) over 3 positive lymph nodes (pN2) were detected. Sixty-three percent, 21% and 14% of the subjects were affected, respectively, by middle differentiation grade (G2), high differentiation grade (G1) and low differentiation grade (G3) carcinomas. In 40,4% of cases mucinous adenocarcinoma cells were identified. Results: ; Similar to other published papers in medical literature, mean plasma ghrelin concentration decreased statistically significantly after 60 and 120 minute in the postprandial period both in male and female control group (respectively p=0.001 and p=0.01; p<0.001 and p<0.001). It proves the proper selection of the control group and correctness of the study protocol. In contrast to the control and male CRC group there was no statistically significant decrease in ghrelin concentration among female patients (p=0.08). Furthermore, there was a statistically significant increase in postoperative fasting ghrelin concentration among female patients (p=0.01), what was not observed in CRC male group (p=0.2). Mean fasting plasma ghrelin concentration in healthy female control group was statistically significantly increased in comparison to CRC female group (p=0.048). Mean fasting plasma ghrelin concentration in healthy male control group was lower in comparison to CRC male group, but the difference was not statistically significant. As expected, comparison of patients based on gender and body mass index (BMI), according to WHO calculation, showed lower mean fasting and postprandial plasma ghrelin concentration among overweight and obese patients (BMI >25 kg/m2), but the differences were not statistically significant. Mean plasma ghrelin concentration fell statistically ; significantly after 120 minutes postprandialy in CRC male group with normal weight (BMI 18.5-24.9 kg/m2) (p=0.04). Due to small number of subjects in CRC overweight/obese male group no statistically significant decrease of postprandial mean plasma ghrelin concentration was noticed (p=0.27). Among CRC female group with normal weight and overweight/obese group there was no statistically significantly decrease in postprandial mean plasma ghrelin concentration (p=0.85). There were no differences in mean fasting plasma ghrelin concentration between subgroups divided based on location of CRC. Making comparison in terms of gender, statistically significantly lower level of plasma ghrelin among CRC female group than in male CRC group in colon was observed. Furthermore, there was no statistically significantly difference in mean fasting plasma ghrelin concentration in subgroups divided in respect of invasion grade pT (p=0.53), presence of lymph nodes metastasis pN (p=0.95), differentiation grade (p=0.36), Dukes, Astler-Coller staging (p=0.96), presence of mucinous adenocarcinoma cells (p=0.6) and type of performed operation (p=0.33). Age, weight (in contrast to the healthy control group), height, total lymphocyte count, plasma albumin and protein concentration and preoperative CEA level was found to be not correlated with the fasting ghrelin concentrations. ROC cur ; ve analysis showed that fasting plasma ghrelin concentration can be useful in risk assessment of colorectal cancer disease with cut-off point ≤18.43 pg/ml (sensitivity 37.5%, specificity 95.2%; likelihood ratio 7.87) in female group. ROC curve analysis showed that changes in postprandial plasma ghrelin concentration can be useful in risk assessment of colorectal cancer disease with cut-off point ≤ 1.68 pg/ml (sensitivity 86.7%, specificity 85.7%; likelihood ratio 6.1) in female group. Conclusion: Ghrelin could be one of the primary risk factors of developing colorectal cancer in female because of the confirmation statistically significant difference in fasting and postprandial plasma ghrelin level between healthy control and CRC female group. The lack of difference in plasma ghrelin concentration between various stages and cell differentiation grade of CRC suggests that ghrelin exerts its activity in the early period of CRC carcinogenesis. Furthermore, the progression of the disease disturbs the correlation between BMI and plasma ghrelin level, which was observed in healthy control group. Radical resection of the CRC has no influence on plasma ghrelin level what, in turn, negates influence of the tumor alone on observed changes. However, identified changes in plasma ghrelin concentration among female with CRC may be used to assess risk of developing CRC in ; this group of patients.
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choroby układu trawiennego ; onkologia