The Diagnostic Value Of Serum Angiogenin In The Early Detection Of Colorectal Cancer

BackgroundColorectal cancer(CRC)is one of the most common malignant tumors of digestive tract,which is a serious threat to human health.Its incidence and mortality all rank in the forefront of tumor spectrum worldwide.Early diagnosis is the key to improve the cure rate and reduce the mortality of colorectal cancer.Up to now,however,there is no ideal noninvasive method for early diagnosis of colorectal cancer.Angiogenin(ANG)plays dual role in angiogenesis and tumorigenesis.Many studies have found abnormal expression of serum ANG level in colorectal cancer patients,ANG is thus considered to be an ideal target for tumor diagnosis.ObjectiveTo investigate serum levels of ANG in patients with advanced colorectal adenoma and colorectal cancer,and to explore the feasibility of serum ANG serving as a biomarker for early detection of colorectal neoplasia.MethodSerum samples from 781 participants,including 369 colorectal cancer patients,133 advanced colorectal adenoma patients and 279 healthy controls(HCs),and their basic information and clinicopathological data were collected.The serum level of ANG was detected by enzyme-linked immunosorbent assay(ELISA).Receiver operating characteristic curves(ROCs)were plotted to analyze the diagnostic accuracy of ANG,and the diagnostic accuracy of ANG was compared to that of two serum biomarkers:carcinoembryonic antigen(carcinoembryonic antigen,CEA)and carbohydrate antigen(carbohydrate antigen,CA19-9),which have been currently used in clinics.We then analyzed the correlation among them and the feasibility of serum ANG as a biomarker for early detection of colorectal cancer comprehensively.SAS 9.2 and GraphPad Prism 5.01 software were used for statistical analysis.ResultsSerum ANG levels increased significantly in patients with advanced colorectal adenomas and colorectal cancer compared to healthy controls(p<0.01).There was no correlation between the serum level of ANG and CEA,ANG and CA19-9 in colorectal cancer patients(p = 0.5447;p = 0.3745),the serum level of CEA was positively-correlated with CA19-9(r = 0.44,p<0.01).The diagnostic value of serum ANG in the diagnosis of colorectal cancer is close to the serum CEA(AUC = 0.74,AUC = 0.77,p =0.26),and significantly higher than that of serum CA19-9(AUC = 0.636,p<0.01).Combined diagnosis of three serum biomarkers of ANG,CEA and CA19-9 can improve the diagnostic value,and the diagnostic accuracy was significantly higher than that of any single serum marker(AUC = 0.8398,p<0.01).The serum level of ANG was not correlated with different TNM stages of colorectal cancers,however,after surgical resection,serum ANG level was significantly decreased(p<0.01).Serum ANG had a diagnostic value of 0.6896 in advanced colorectal adenoma(AUC-0.6896),and serum CEA and CA19-9 had no diagnostic value for advanced colorectal adenoma.Therefore,we recommend that serum ANG is more suitable to serve as a marker for the detection of colorectal neoplasia.Combined with the risk factor of colorectal cancer,we established a diagnosis model(Logit(P)=-17.8190 + 0.0437Xi + 2.5625X2-2.5124X3-0.3194X4-0.6428X5+ 2.5274X6,Xi = age,X2= InANG,X3= marital status,X4 =education level,X5 = the total annual income of family,X6 = labor intensity).ConclusionsThe aim of this study is to detect serum ANG level in patients with advanced colorectal adenoma,colorectal cancer and healthy controls,and to explore the feasibility of serum ANG for serving as a biomarker for early detection of colorectal cancer.Based on our results,we concluded:1.Serum ANG was highly expressed in patients with advanced colorectal adenoma and colorectal cancer.2.There was no correlation between the level of serum ANG and CEA,ANG and CA19-9 in colorectal cancer patients,and the serum level of CEA was positively related to CA19-9.3.Serum ANG and CEA had better diagnostic ability for colorectal cancer than that of serum CA19-9,and there was no statistical difference between them.Combined diagnosis of serum ANG,CEA and CA19-9 could improve the sensitivity and diagnostic accuracy.4.Serum ANG was not related to different TNM stages of colorectal cancer and could not be used to assess the clinicopathological stages of colorectal cancer.5.The level of serum ANG decreased significantly after resection of colorectal cancer.6.Serum ANG had the potential to serve as a diagnostic biomarker for colorectal adenoma.Serum CEA and CA19-9 have no diagnostic value for colorectal adenoma.7.Combined use of serum ANG and other risk factors for detection of colorectal cancer could improve the diagnostic value effectively.In conclusion,serum ANG is a potential biomarker for early diagnosis of colorectal cancer.It can be used to screen high-risk patients for further colonoscopy,so as to improve the detection rate of colorectal cancer.