| Objective:Colorectal cancer(CRC)is the second most commonly diagnosed cancer in women and third in men.Westernized lifestyle significantly increases the prevalence of obesity and physical inactivity in recent decades and may have contributed to the increase in the incidence of CRC.To date,TNM staging has been the most commonly used prognostic indicator.However,the survival difference exists within the same TNM stage.Host factors such as the systemic inflammation may be responsible for the observed differences in survival.Therefore,the development of simple,non-invasive methods is important for the accurate assessment of patient prognosis.Fibrinogen is a soluble glycoprotein produced by hepatocytes and converted into fibrin by activated thrombin.It plays a major role in blood clotting,cellular and matrix interactions,and wound healing.In addition,fibrinogen may be affected by the presence of inflammation.However,the mechanism involved in the synthesis of activated fibrinogen during inflammation is not fully understood.Studies have shown that higher levels of fibrinogen are correlated with an increased risk of developing CRC.The prognostic role of preoperative fibrinogen in CRC patients remains controversial.Son et al.suggested that elevated fibrinogen levels may serve as a prognostic indicator in patients with nonmetastatic colon cancer.However,Pedrazzani et al.showed that preoperative fibrinogen levels associated with major prognostic factor but did not help predict patient outcome after CRC surgery.The primary objective of this study was to investigate the prognostic prediction value of preoperative fibrinogen level in nonmetastatic CRC.The secondary objective was to construct predictive models and nomograms to predict the survival of nonmetastatic CRC patients.Methods:1.Patient cohort:We retrospectively analyzed a cohort of CRC patients who underwent primary tumor resection at the Department of Surgical Oncology at the First Hospital of China Medical University(CMU-SO).Patients without recorded preoperative fibrinogen levels,those with metastatic disease,and those who received preoperative chemoradiotherapy were excluded.Therefore,1869 patients were included in the study.Follow-up was completed until October 2015.Median follow-up was 46 months(range of 4-136).Clinical data,including age,sex,clinicopathological features,and preoperative laboratory data,were obtained from the medical records of the patients.Blood parameters were measured in early-morning samples collected 1 to 14 days before surgery.The albumin level was obtained using the hepatic function test,and neutrophil,lymphocyte,and platelet counts were collected using a routine blood test.PNI was calculated as 10×albumin level(g/dl)+0.005×total lymphocyte count(per mm~3).The CRC stage was classified according to the eighth edition of the AJCC/UICC TNM classification system.2.Statistical analysis:Categorical variables were presented as absolute values.The association between preoperative fibrinogen levels and clinicopathologic data was evaluated using nonparametric tests and Spearman rank-order correlation.Survival curves were depicted using the Kaplan-Meier method and compared using the log-rank test.Significant prognostic factors for OS and CSS were included in the multivariate Cox regression analysis by using a backward step-wise method.The performance in predicting the outcome was evaluated with the c-index,which is equivalent to the area under the receiver operating characteristic curve.The maximum c-index value(1.0)indicates perfect prediction,whereas 0.5 indicates a random chance of correct prediction.Nomograms were formulated on the basis of the results of the multivariate Cox regression analysis.Calibration was assessed by comparing nomogram-predicted versus observed outcomes.We quantified discrimination and determined the optimal cut-off values for inflammatory biomarkers using the Bayesian information criterion(BIC).A smaller BIC value indicated a better model for predicting the outcome.Restricted cubic spline functions were used to estimate the dose-response association between the continuous variable and the outcome.Results:1.Preoperative fibrinogen levels were significantly correlated with age,tumor differentiation,tumor location,pT category,and TNM stage(P<0.05)but were not significantly associated with sex(P=0.299)and pN category(P=0.359).2.In the multivariate analysis,elevated fibrinogen level was independently correlated with worse OS and CSS(OS:hazard ratio[HR]=0.777,95%confidence interval[95%CI]=0.630–0.958,P=0.018;CSS:HR=0.757,95%CI=0.605–0.947,P=0.015).3.The nomograms could predict outcomes,with a c-index for OS and CSS of 0.79 and 0.81,respectively.The nomograms also had a good calibration.Conclusion:Preoperative fibrinogen level was an independent marker of poor prognosis in patients with nonmetastatic CRC,and there was a threshold level for the use of fibrinogen as a prognostic factor.The developed nomograms can help predict the individual risk of OS and CSS in patients operated for CRC. |
PDF Full Text Request