The Application, Identification And Screening Of Biomarkers In Colorectal Cancer

Purpose:To assess the influence of existing tumor biomarkers on colorectal patients’ prognosis, to look for new factors to predict prognosis of colorectal cancer, to explore new methods to screen new tumor biomarkers.Methods:Part Ⅰ:Retrospectively collecting573patients who had received radical resection for stage Ⅱ～Ⅱ colorectal cancer in the cancer hospital of Fudan University from2003to2009, univariate and multivariate analysis were used to investigate the relationship between CEA/CA19-9and patients’survivals.Part Ⅱ:Retrospectively collecting77frozen tissues and59parrafin-embedded samples from patients who had received radical resection for stage Ⅱ/Ⅲ colorectal cancer in cancer hospital of Fudan University from2006to2008, real time PCR and immunohistochemistry were used to investigate the relationship between MYH11expression and recurrence or metastasis.Part Ⅲ:Collecting20tumor and paired normal tissue from patients who had received radical resecton for colorectal cancer in cancer hospital of Fudan University in Oct.2012. MALDI-TOF MS was used to screen potential tumor biomarkers.Results:Part Ⅰ:In univariate analysis, differentiation(P<0.001), histological type (P=0.010), number of lymph node metastases(P<0.001), and elevated levels of CEA (P<0.001) and CA19-9(P<0.001) were closely correlated with patients’ survival; patients who had both CEA and CA19-9positive values had the worst prognosis, whereas those who had both CEA and CA19-9negative values had the best prognosis (P<0.001). In multivariate analysis, the number of lymph node metastases(P<0.001), preoperative CA19-9(P=0.007) and CEA(P=0.022) values were independent prognostic factors for survival.Part Ⅱ:The expression of gene MYH11is higher in patients without recurrence/metastasis than patients with recurrence/metastasis in both mRNA level(P=0.009) and protein level(P=0.002). In the study of the relationship between MYH11expression and patients’ clinicopathologic characteristics, the expression of MYH11has no relationship with patients’ clinicopathologic characteristics. In univariate analysis, nerve invasion(P=0.002) and intravascular emboli(P=0.003) and MYH11expression(P=0.004) are related to patients’ disease-free survival, low expression of MYH11is related to short disease-free survival. In multivariate analysis, MYH11gene is considered as independent prognostic predictor of stage Ⅱ/Ⅲ colorectal cancer(P=0.030). Part Ⅲ:Six proteomic features demonstrated highly successful diagnostic performance (m/z):6727(P=0.005),7953(P=0.003),8589(P=0.044),10319(P=0.027),15138(P=0.015),15876(P=0.010).Conclusion:Part Ⅰ:Preoperative CA19-9and CEA have independent prognostic values in stage Ⅱ～Ⅱ colorectal cancer. Elevation of and both CEA and CA19-9values predicted the worst outcome.Part Ⅱ:MYH11is a potential biomarker for prognosis in stage Ⅱ/Ⅲ colorectal cancer and its low expression will indicate recurrence or metastasis.Part Ⅲ:MALDI-TOF MS can be used to analyze the tissue proteomic expression difference of colorectal cancer for early diagnosis and screen new tumor biomarkers.