Prognostic Value Of Serum Uric Acid And Gamma-glutamyltransferase In Patients With Advanced Gastric Cancer

Objective: Several studies demonstrated that a variety of hematological markers are effective prognostic indicators for advanced gastric cancer.Elevation of serum uric acid and gamma-glutamyltransferase is associated with tumorigenesis,development,and mortality.However,the relationship with malignant tumors is not yet fully understood and remains controversial.The aim of this study was to investigate the prognostic value of serum uric acid and ?-glutamyltransferase in patients with advanced gastric cancer.We establish a nomogram for advanced gastric cancer,which could provide individualized predictive models for advanced gastric cancer.Methods: A total of 180 patients who were pathologically diagnosed with advanced gastric cancer were included in this retrospective study.Clinicopathological data were extracted at the time of diagnosis,including age,sex,histopathological records,diagnosis,TNM stage,serum uric acid,?-glutamyltransferase,pathology,blood routine and tumor markers.And treatment protocols,progression-free survival time and overall survival time were obtained during the follow-up period.At the same time,an independent cohort of 60 patients who were pathologically diagnosed with advanced gastric cancer at other medical center was studied,using the same inclusion and exclusion criteria.The receiver operating characteristic(ROC)curve was plotted using SPSS software to determine the optimal cut-off values for serum uric acid(UA)and gamma-glutamyltransferase(GGT).Survival analysis and survival curves were performed using Kaplan-Meier method and log-rank test;and univariate and multivariate Cox regression analyses were applied.A nomogram was formulated by R.In order to verify the discrimination and consistency of the nomogram,internal verification and external verification are performed.The predictive accuracy and discriminative ability of the nomogram were determined by concordance index(C-index)and calibration curve.The results were validated using bootstrap resampling and a separate study on 60 patients collected from 2015 to 2017 using the same criteria in other medical center.Result: We performed ROC curve analysis to determine the optimal cut-off value based on the largest Youden's index.An SUA of 284 ?mol/L calculated by ROC curve showed the best specificity and sensitivity,and the area under the curve(AUC)of SUA was 0.694(95% confidence interval[CI]: 0.616-0.773,p<0.001).The cut-off value of GGT was23.05 U/L,with an AUC of 0.717(95% CI: 0.640–0.793,p<0.001;Figure 1B).Based on the cut-off value,57 patients(31.7%)had an elevated SUA,while 66 patients(36.7%)had an elevated GGT.Both higher serum uric acid(>284?mol/L)and higher gamma-glutamyltransferase(>23.05 U/L)had worse OS and PFS.Univariate analysis revealed that serum uric acid(UA)(p<0.001 and p<0.001)and gamma-glutamyltransferase(GGT)(p<0.001 and p=0.044)were significantly associated with overall survival and progression-free survival,respectively.Multivariate analysis identified serum uric acid(UA)and gamma-glutamyltransferase(GGT)as independent prognostic factors for OS(p=0.012,p=0.001).Based on the results of the multivariate analysis,the nomogram is drawn by R language.The internal verification predicts that the C index of the discrimination is 0.748(95% CI: 0.70-0.79),suggesting that the nomogram has a better discrimination.The calibration curve for the 1-or 2-year survival probability shows the best agreement between the nomogram prediction and the actual survival probability,indicating that the prediction of the nomogram is well consistent.In external verification,the C-index and the calibration curve show that the nomogram has good discrimination and consistency.Conclusion: Our study showed that serum UA and GGT are independent prognostic factors in patients with advanced gastric cancer.And we also established and validated a novel nomogram that can provide individual prediction of OS for patients with advanced gastric cancer.