Studys On Diagnosis Of Colorectal Cancer With Fecal Calprotectin

[Background and Purpose]Colorectal cancer ( CRC), the second most common cancer in westen countries, remains the second cause of over all malignant mortality in the United States. With the improvement of economy and living in china, the incidence of CRC rises rapidly. It takes about ten years that colonic epithelial cells becomed to carcinoma from the adenomatous dysplasia neoplasia, and it costs about five years from the identifiable adenoma to invasive carcinoma. Thus there were sufficient time to screen early CRC, even to prevent and treat. CRC could be most effectively treated at an early stage, but the early stage of CRC is mostly symptomless as well as delitescence nature. Approximately 40% patients of CRC were diagnosed at asymptomatic period, and 70%~90% of them survived for five years after surgery. However, with the poor prognosis of advanced CRC, the five-year survival rate of patients with distant metastasis is only 5%.With detecting and removing lesions that may potentially develop into cancer, we can reduce the incidence of colorectal cancer and improve primary prevention and survival rate. Therefore, the early detection for high-risk groups is the key, and an effective screening test would have substantial clinical benefits. It is difficult to reduce CRC incidence rate by changing people's lifestyle. However, CRC screening will appropriately decline mortality, which may decrease the incidence of CRC through detection and removal of colorectal adenoma (early less invasive surgical treatment or endoscopic resection). Now that most of early diagnostic techniques such as fecal occult blood test, barium enema and electronic colonoscopy were low accuracy, high cost, invasiveness, low patient compliance, even serious complications such as intestinal bleeding and perforation and so on. So these methods are not suitable for screening. Therefore, exploring a safe, reliable, specific, effective early CRC screening method is the urgent medical problem to be solved.Specific tumor markers of colorectal cancer in faeces come from the shedding of tumor cells, and the sustainable release of these markers can be detected. The protein markers in faeces can be divided into two categories, one category is from non-colonic epithelial cells, such as calprotectin, etc, and the other protein markers for colorectal epithelial are cell's own proteins, such as carcinoembryonic antigen (CEA). Now China is formulating colorectal cancer screening of the general populations, the guidelines to monitor high-risk groups. Many experts and scholars are exploring to plan CRC screening programs which is suitable to our country's national conditions, such as sequential fecal occult blood test in the North has achieved some success. In this study, we assayed fecal calprotectin and carcinoembryonic antigen levels by ELISA to determine their diagnostic cut-off value of colorectal cancer, then selected several serum tumor markers of colorectal cancer and combined a rational group which was verified by a set of consecutive cases with double blind, in order to explore and establish a non-invasive colorectal cancer screening program.[Methods]These studys are divided into three parts.Part 1. Study on the fecal calprotectin and carcinoembryonic antigen as a potential biomarker for colorectal cancer1. Object According to the diagnosis of colonoscopy or surgical pathology,206 Patients were divided into 4 groups: the control group(73 cases), colorectal polyps group(61 cases) , IBD group (29) and colorectal cancer (48 cases).2. Methods About 10～20g stools had been collected before colonoscopy. These stools were stored at 2-8℃within 6 days, and extraction were cryopreserved at -20℃place. ELISA was used to measure the concentrations of the calprotectin and carcinoembryonic antigen..Part 2. Study on feasibility Analysis to diagnose colorectal cancer with serum tumor markers1. Object Serum tumor markers (CEA, CA72-4, CA199, AFP, TSGF) were detected in210 patients addmiting in the Department of Gastroenterology, Beijing Army General Hospital from Nov.2006 to Apr.2008. According to the diagnosis of colonoscopy or surgical pathology,Patients were divided into 3 groups: colorectal cancer (43 cases, including 25 cases of colon cancer, 15 cases of rectal cancer, 3 cases of lymphoma), colorectal polyps (66 cases, including 29 cases of inflammatory polyps, 29 cases of colorectal tubular adenomas, eight cases of tubular villous adenoma) and control (69 cases, physical examination were normal and no heart, liver, kidney, lungs and other vital organs diseases, colonoscopy no abnormal lesions). 2. Methods The area under the ROC curve(AUC)s of CEA, CA199, CA72-4, AFP, TSGF from logistic regression results were contrasted and then a reasonable scheme was obtained .Part 3. Study on efficiency evaluation to diagnose of colorectal cancer with fecal calprotectin and serum tumor markersBased on the principle of double-blind, according to inclusive standards and exclusive criteria, 184 consecutive cases with the symptoms of abdominal discomfort needed colonoscopy detection were included. The FOBT, serum CRP, serum tumor markers, stool calprotectin were detected after admitted. According to the diagnosis of colonoscopy or surgical pathology,the patients were divided into groups at the end of trial. The sensitivity, specificity, Youden's index and ROC curve were calculated by SPSS.[Results]1. The fecal calprotection concentration is the highest among patients of inflammatory bowel diseases, followed by group for colorectal cancer, non-cancerous colon polyps, and normal control group. There were significantly differences between groups (p <0.05);The fecal CEA concentration among patients of colorectal cancer group was significantly higher than that of non-cancerous colon polyp group, inflammatory bowel disease group, normal control group, the level in inflammatory bowel disease group was also higher than that of normal control group (p<0.05).But there was no difference in CEA between non-cancerous polyps group and control group (P>0.05). The fecal calprotectin and the level of CEA did not associate with tumor location (p> 0.05).Cut off value of fecal calprotectin was 113.23μg/g . The predicting sensitivity and specificity of fecal calprotectin were 93.6% and 67.2%. Its area under the ROC curve was 0.827; Cutoff value of fecal carcinoembryonic antigen was 8.245μg/g The predicting sensitivity and specificity was 75% and 49.2%, the area under the ROC curve was 0.652; The both detection of colorectal cancer area under the ROC curve was 0.81, could not improve diagnostic efficiency.2. The mean concentrations and positive rate of CEA, CA72-4, CA199, AFP, TSGF in colorectal cancer and non-cancerous colon polyp group were significantly different(P <0.05); Fitted best curves by gradually logistic regression, the AUC of CEA was highest, followed by CA72-4, CA19-9. The AUC of AFP and TSGF was close to 0.5, the accuracy of differential diagnosis is lower; The useful items were selected after analyzing the data with logistic regression, the AUC of CEA + CA72-4 + TSGF (0.950) were higher than that of themselves in order to distinguish colorectal cancer with non-cancerous colon polyp (P<0.05).3. Their diagnostic value of our study was evaluated by ROC. The value of accuracy and screening of faecal calprotectin was highest. Its sensitivity of diagnosis in colorectal cancer was 93.3%, specificity was 76%. The sensitivity of CEA+CA72-4+TSGF was 62.5%, specificity was 88%. When the non-cancerous colon polyp group was used as the control, the areas of under ROC curve (AUC)of CRP, CEA + CA72-4 + TSGF were 0.734,0.811, 0.792 respectively. There was significantly different between them and 0.5.[Conclusion]1. Faecal calprotectin detcetion is an ideal method in screening for colorectal cancer.2. Tumor markers can improve the clinical accuracy of detection in colorectal cancer, CEA + CA72-4 + TSGF more efficient than a single detection diagnosis, also reduce the unnecessary number of tumor markers and reduced patient financial burden.3. Faecal calprotectin has higher sensitivity, tumor markers CEA + CA72-4 + TSGF portfolio can compensate for its lack of specificity, and the both have a certain degree of accuracy. According to the principle of the first broad-spectrum post-specific, and the first characterization after positioning, we should firstly measure fecal calprotectin, at the same time detect CEA + CA72-4 + TSGF, and then to do endoscopy or imaging examination when we get positive results. This can realize regular tumor screening in high-risk groups for early detection and early treatment, and this approach is easier to be accepted, and has a good compliance. The clinical value of measurement is important.