Clinicopathological parameters of HCC patients
By comparative analyzing of clinicopathological parameters of MVI group (n = 115) and non-MVI group (n = 115), it was found that the level of GLR in MVI group and non-MVI group was 84.83 ± 61.84 and 38.42 ± 33.52, respectively (p < 0.001). Except for GLR level, MVI group was higher than non-MVI group in tumor size, neutrophil cell count (NEUT), white blood cel (WBC), Globulin, direct bilirubin (DBIL), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and GGT (all p < 0.05), while lymphocyte count (LYMPH) and albumin were lower than those in the non-MVI group (p < 0.05) (Table 1). In addition, we found that there was a positive correlation between GLR level and AST level (r = 0.347, p < 0.001) (Fig. 1B). These results suggest that inflammatory factors, such as NEUT, WBC, Globulin and AST, increase the risk of MVI in patients with HCC, and GLR acts as an inflammatory factor.
Optimal cut-off value of GLR
The ROC curve was drawn and analyzed according to the existence of MVI in patients with HCC, the optimum cut-off value of GLR is 56, the area under the ROC curve (AUC) is 0.781, with the 95% confidence interval (95% CI) is 0.719 - 0.833. The sensitivity and specificity were 63.6% and 81.7% when the cut-off value of GLR was 56 (Fig. 1A). The results suggest that GLR may be a potential predictor for HCC complicated with MVI. In addition, in the following studies, we found that when the cut-off value of GLR was 56,GLR had certain application value in predicting postoperative survival of patients who had HCC and who had HCC combined with MVI subgroup.
Univariate analysis and multivariate cox regression analysis
In Univariate Cox regression analysis, GLR > 56 was found to be a risk factor for postoperative PFS (HR = 2.36, 95% CI, 1.53 ≤ 3.08, p < 0.001) and OS (HR = 2.47, 95% CI, 1.80 ≤ 3.40, p < 0.001). In addition to GLR > 56, the adverse factors of postoperative OS and PFS included multiple tumor nodules, tumor size > 5 cm, MVI and AFP > 20 ng/ml. The statistically significant factors in univariate analysis were further analyzed by Cox proportional risk regression model to perform multivariate analysis. It was found that GLR > 56 was an independent risk factor for postoperative HCC PFS (HR = 1.56, 95 % CI, 1.18 ≤ 2.36, p = 0.017) and OS (HR = 1.63, 95% CI, 1.28 ≤ 2.31, p = 0.006). In addition, tumor size > 5 cm and combined MVI can be used as independent risk factors for poor PFS and OS in HCC patients (Table 2).
The value of MVI and GLR in postoperative survival and prognosis of patients with HCC
Kaplan-Meier analysis showed that the mean PFS and OS of non-MVI group (n = 115) were 51.1 months and 59.3 months, and those of MVI group (n = 115) were 26.9 months and 34.5 months, respectively. PFS of non-MVI group for 1 year, 3 years and 5 years was also significantly higher than those of MVI group (73.6% vs. 59.4%, 58.7% vs. 25.9% and 49.3% vs. 13.1%, respectively, all p < 0.001) (Fig. 2A). Similarly, the OS of the patients in non-MVI group at 1 year, 3 years and 5 years was significantly higher than those of MVI group (88.1% vs. 66.8%, 73.0% vs. 37.1% and 61.4% vs. 17.9%, p < 0.001) (Fig. 2B). In addition, we further discussed the postoperative survival and prognosis of M1 (n = 70) and M2 (n = 45) subgroups in the MVI group. Compared with M2 group patients, M1 group patients had longer PFS (p = 0.019) (Fig. 2C) and OS (p = 0.010) (Fig. 2D).
Of these 230 HCC patients involved in this study, compared with GLR ≤ 56 group (n = 138), GLR > 56 group (n = 92) had shorter mean PFS (46.9 months vs 28.1 months, p < 0.001) and OS (55.8 months vs 33.4 months, p < 0.001) (Fig. 3A, B). More interesting is that in M1 group patients (n = 70), patients with GLR > 56 (n = 38) had shorter mean PFS (36.7 months vs 21.5 months, p = 0.012) and mean OS (43.8 months vs 31.2 months, p = 0.031) (Fig. 3C, D). This indicates that GLR can also play a prognostic role in M1 group of HCC patients.
These results suggest that MVI(MVI subgroup) and GLR level are closely related to postoperative survival and prognosis of patients with HCC after operation.