br Results br The correlations of PLR and serum CA
The correlations of PLR and serum CA19-9 level to clinicopatho-logical variables are shown in Table 1. Patients with larger tumors (≥ 29.4 mm), those with a tumor located in the pancreas head, and those with lymph node metastasis had a significantly higher PLR than patients with smaller tumors (P = 0.002), those with a tumor located in the pancreas body and tail (P = 0.021), and those with-out lymph node metastasis (P = 0.010), respectively. Patients with lymph node metastasis and those with lymphatic vessel invasion had a significantly higher serum CA19-9 level than those without lymph node metastasis (P = 0.003) and those without lymphatic vessel invasion (P = 0.022), respectively.
ROC analysis with respect to the 5-year OS rate indicated that the highest Youden indices (sensitivity + specificity − 1) with
Fig. 1. The correlation between the PLR and serum CA19-9 level. PLR: platelet-to-
Correlations of PLR and serum CA19-9 level to clinicopathological variables in patients with resected pan-
Lymph node metastasis
Lymphatic vessel invasionc
a Data not available for two patients.
b G1, well-differentiated; G2, moderately differentiated; G3, poorly differentiated; G4, undifferentiated. c Grade of lymphatic vessel invasion. d Grade of vessel invasion. e Grade of perineural invasion. PLR: platelet-to-lymphocyte ratio; CA19-9: carbohydrate antigen 19–9.
Univariate analysis indicated that lymph node metastasis, lym-phatic vessel invasion, perineural invasion, and the combination of PLR and serum CA19-9 level were significantly associated with OS (Table 2). We next included covariates with P < 0.1 in uni-variate analysis into the multivariate analysis. Multivariate analy-sis revealed that the combination of the PLR and serum CA19-9
In this study, we first demonstrated that the PLR was closely associated with the prognosis of patients with resectable PC. The PLR consists of the peripheral platelet count and lymphocyte count and is considered to be an inflammatory indicator. A high PLR reflects an increased platelet count. Thrombocytosis is detected in 10% to 57% of patients with malignancy because many types of neoplastic AMG-176 stimulate platelet activation . One of the mechanisms responsible for thrombocytosis might be the secre-tion of factors such as interleukin-6 (IL-6) and vascular endothe-lial growth factor (VEGF) by the cancer cells themselves and the cancer microenvironment. IL-6 has an important role in reactive thrombocytosis based on its cell-proliferative effect because it trig-gers the differentiation of megakaryocytes to platelets in the bone marrow [18,19]. VEGF also stimulates the differentiation of megakaryocytes to platelets . Studies have shown that the serum concentrations of IL-6 and VEGF are significantly higher in patients with PC than in healthy subjects [21,22]. Both IL-6 and VEGF are associated with the prognosis of patients with var-ious types of cancers including PC [23,24]. Therefore, thrombocy-tosis indirectly reflects tumor progression. Furthermore, platelets themselves have a direct effect on cancer progression by inter-acting with malignant cells to promote metastasis . They also enhance the sequestration, adherence, and penetration of malig-nant cells through the endothelium, prevent the immune system
Fig. 2. Overall survival curve (A) and disease-specific survival curve (B) according to the PLR. PLR: platelet-to-lymphocyte ratio.
Fig. 3. Overall survival curve (A) and disease-specific survival curve (B) according to the serum CA19-9 level. CA19-9: carbohydrate antigen 19–9.
Fig. 4. Overall survival curve (A) and disease-specific survival curve (B) according to combination of PLR and serum CA19-9 level. PLR: platelet-to-lymphocyte ratio; CA19-9:
carbohydrate antigen 19–9.
Univariate and multivariate analyses of prognostic factors for overall survival in patients with resected pancreatic cancer.
Summary of published studies that determined prognostic significance of preoperative platelet-to-lymphocyte ratio in patients with pan-creatic cancer.
Studies Year No. of patients Study design Cutoff value Survival outcome Statistical significance
Advanced pancreatic cancer
103 Retrospective 129.1 OS Present
from clearing tumor cells from the circulatory system , and are the source of thymidine phosphorylase/platelet-derived endothe-lial cell growth factor, which has both mitogenic and angiogenic activity . These observations can account for the association of reactive thrombocytosis with survival in patients undergoing surgery for several types of cancer including PC.