The Association Between Hyperfibrinogenemia And Clinicopathological Factors, And The Survival Analysis Of Gastric Cancer

Objective: Gastric cancer(GC)is one of the most common malignant tumors in the world, ranked of the fourth in the incidence of global cancer. It is reported that hyperfibrinogenemia and other elevated parameters which reflect systemic inflammation are commonly seen in cancer patients and be useful predictors of poor prognosis in GC. The studies which explore the relationship between the level of fibrinogen as well as other inflammatory markers in plasma and GC are rarely reported in our country. This paper aim to discuss the precise association between such plasma markers and preoperative clinicopathological factors and to evaluate the value as predictors of prognosis.Method: Retrospectively reviewed the medical records and follow-up data of patients with nonmetastatic GC who underwent curative resection from January 2010 to December 2013 at Surgery Department of the Fourth Hospital of Hebei Medical University. Fibrinogen, gastric tumor markers and other inflammatory parameters were measured a week before the surgery by our hospital laboratory who give us the accurate results. Statistical analysis was carried out by SPSS 13.0 so that we can find out the relationship between such inflammatory markers and preoperative clinicopathological factors and evaluate the significance as predictors of prognosis.Consequence:1 A total of 248 cases who underwent curative surgery were enrolled in this study, all of them have complete operative clinical and follow-up data. The means±SD of preoperative plasma fibrinogen level in our study was 3.28±1.06g/L. In the present study, fibrinogen levels were higher in older patients(≥60years),advanced tumor, poorly differentiated tumor, deep invasion, lymph node metastasis, large tumor size and in those with high carcinoembryonic antigen(CEA) and inflammatory parameters such as platelet count, albumin, neutrophil:lymphocyte ratios(NLR) and platelet:lymphocyte ratios(PLR), P<0.05.2 All patients were divided by the TNM staging system into 3 groups and found that the mean values of plasma fibrinogen were significantly high in stage Ⅱ and Ⅲ patients compared with stage Ⅰ and the differences were significant statistically(stage Ⅰ vs. stage Ⅱ : 2.84±0.72g/L vs. 3.36±1.18g/L,P=0.009;stage Ⅰ vs. stage Ⅲ : 2.84±0.72g/L vs. 3.43±1.07g/L,P<0.001), however, there was no difference between stageⅡand Ⅲ patients(P=0.662). When the patients were classified into 4 groups according to the T classification, the plasma fibrinogen levels were not only statistically different among them but also gradually increased with increasing depth of cancer invasion(one way ANOVA;P=0.002). When the patients who have lymph nodes metastasis classified according to the N classification into three sets,note that mean values of plasma fibrinogen level gradually increase in accordance with the elevation of the extent of lymph node metastasis. Yet, the differences among them did not have statistically significance(P=0.333).3 Tumor location, differentiation, pathological type, tumor size, tumor markers—CEA, CA19-9, CA72-4 as well as inflammatory parameters—platelet count, fibrinogen, albumin and PLR showed a positive association with advanced cancer(T>T1, based on pathology) in univariate analysis. Multivariate analysis revealed that high inflammatory parameters levels—fibrinogen(odds ratio,2.686(1.012-7.125);P=0.047),albumin(odds ratio,0.422(0.179-0.999);P=0.050), poorly differentiated as well as large tumor size had an independent association with advanced cancer.4 Univariate analysis showed that lymph node metastasis were significantly associated with many factors such as sex, tumor markers—CEA, CA19-9 and inflammatory parameters—fibrinogen, albumin and NLR. Multivariate analysis explained that inflammatory parameters—fibrinogen(odds ratio,2.012(1.012-3.125);P=0.035),albumin(odds ratio,2.311(1.239-4.309);P=0.008) and NLR(odds ratio,0.293(0.099-0.868);P=0.027) showed an independent association with lymph node metastasis, whereas tumor markers—CEA and CA19-9 were not the independent factors.5 Univariate analysis revealed that sex, tumor location, differentiation, pathological type, tumor markers—CEA,CA19-9,CA72-4 and CA50 as well as inflammatory parameters—platelet count,albumin,fibrinogen,NLR and PLR were correlated with tumor size.Fibrinogen(odds ratio,1.949(1.099-3.454);P=0.022),platelet count(odds ratio,2.194(1.046-4.600);P=0.038), tumor markers—CEA,CA19-9,CA72-4 as well as differentiation showed independent association with tumor size in multivariate analysis.6 Our results suggested that the patients with hyperfibrinogenemia before surgery showed a significantly lower survival rate than the lower one in GC, the difference between them is statistically(Log-Rank test;P<0.001). Hyperfibrinogenemia was the main independent predictor on the overall survival(OS), which could predict worse clinical outcome.Conclusion: As our present study suggested, the plasma level of fibrinogen associated with many clinicopathological factors. As one of inflammatory markers, hyperfibrinogenemia may be considered a useful biomarker to predict advanced tumor, lymph node metastasis and large tumor size and can be a good predictor of worse clinical outcome. Compared with imaging examination, routinely tested plasma fibrinogen level before surgery is simple, economical and practical which is benefit to our clinical work.