ABSTRACT
This study was aimed at investigating the potential of cell-free DNA (cfDNA) as a biomarker for colorectal cancer prognosis. Sixty patients with colorectal cancer who had not undergone surgery were enrolled as study group. Their peripheral blood samples were collected, and peripheral blood of 30 healthy volunteers (control) was collected. The cfDNA concentration and integrity were determined using q-PCR so as to ascertain if cfDNA was associated with clinical presentations of the disease. Then, the specificities and sensitivities of cfDNA, CFA and CA199 were determined with ROC curve. The level and integrity of cfDNA in patients with colorectal cancer before surgery were significantly higher than those in patients with colorectal cancer after surgery, and cfDNA concentration of colorectal cancer patients after surgery was also significantly higher than that in healthy control group. However, the integrity was not significantly different from that of control group. There was a significant correlation between cfDNA concentration and TNM stage, differentiation degree and CEA expression, while cfDNA integrity was significantly correlated with TNM stage and degree of differentiation. Moreover, specificity and sensitivity of cfDNA concentration and integrity were higher than those of CEA and CA199. The TNM stage and cfDNA concentration were independent risk factors for progression-free survival (PFS) in colorectal cancer patients. In conclusion, cfDNA concentration and integrity were more sensitive and specific than traditional tumor markers (CA199, CEA). Thus, changes in cfDNA changes can be effectively used to determine the prognosis of postoperative colorectal cancer patients.
Subject(s)
Biomarkers, Tumor/blood , Cell-Free Nucleic Acids/blood , Colorectal Neoplasms/pathology , Adult , Aged , Antigens, Tumor-Associated, Carbohydrate/blood , Area Under Curve , Case-Control Studies , Colorectal Neoplasms/genetics , Colorectal Neoplasms/mortality , Colorectal Neoplasms/surgery , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Prognosis , Progression-Free Survival , Proportional Hazards Models , ROC Curve , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Expressions of Caspase-8 and Caspase-3 have been identified as important markers in many malignant tumors, but their roles in colorectal cancer (CRC) have not been confirmed. The purpose of this study was to investigate the role of Caspase-8 and Caspase-3 in CRC. METHODS: We enrolled 470 CRC patients in this study. Archival paraffin-embedded CRC tissue samples were used to construct tissue microarray (TMA), expressions of Caspase-8 and Caspase-3 that were stained by immunohistochemistry. Prognostic and predictive role of Caspase-8 and Caspase-3 expressions, alone or united, were evaluated by univariate and multivariate analysis respectively. RESULTS: In comparison with adjacent normal tissues, Caspase-8 and Caspase-3 protein levels were upregulated in CRC tissues significantly, furthermore, high expressions of Caspase-8 and Caspase-3 were correlated with decreased overall survival (OS) (p< 0.05), and also with unfavorable clinicopathologic characteristics. Cox regression analysis showed that high Caspase-8 and Caspase-3 expressions were independent negative markers of OS. CONCLUSION: Caspase-8 and Caspase-3 expressions in tumor tissues are novel candidate prognostic markers for CRC patients. It was the first time to be identified that Caspase-8 and Caspase-3 expressions had synergistic role as efficient prognostic indicators for CRC patients.
