Abstract
Objective: To evaluate the importance of preoperative blood platelet to lymphocyte ratio (PLR) in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver surgery and to examine the connection with CD8+ lymph cell infiltration.Methods: Between 2009 and 2014, consecutive HCC patients who received curative liver surgery were included into this retrospective study. Baseline clinicopathological characteristics were analyzed to identify predictors of recurrence-free and overall patient survival rate after liver resection. The samples of all patients were under Tissue Microarray (TMA) construction and immunohistochemical staining for CD8+.The association of the number of CD8+T-cells in the cancer nests and peritumoral stroma with PLR level was analyzed.Results: A total of 1,174 HBV-related HCC patients who received a liver resection without any peri-operative adjuvant therapy were enrolled into this retrospective study. Univariate and Multivariate analysis using Cox regression model showed that PLR was an independent factor affecting recurrence and overall survivals. The optimal cutoff of PLR using the receiver operating characteristic curve was 150. There were 236 patients (20.1%) who had a PLR of 150 or more. The 5-year survival rate after liver resection was 71.8% in patients with a PLR of < 150 and it was 57.2% in those with a PLR of 150 or more (P < 0.001). Both 5-year recurrence-free and overall survival rates in liver cancer stage A patients at Barcelona Clinic with different PLR group were also significantly different (P = 0.007 for recurrence and P = 0.001 for overall survival). Similar results were also observed in stage B patients (P < 0.001 for recurrence and P = 0.033 for overall survival). To determine the association between PLR and the severity of liver inflammation, an immuno-histological examination using CD8+ staining was performed on the liver specimens of 1,174 patients. Compared with low PLR (<150) group, more CD8+T-cells were found in the peritumoral tissue in high PLR (≥ 150) group.Conclusions: PLR played as an independent factor for predicting the survival after hepatectomy for HCC patients. A high PLR was associated with an accumulation of CD8+ T-cells in the peritumoral stroma.
Highlights
Inflammation has been regarded as the seventh symptom of cancer [1]
Thirty seven patients were excluded from this study because of an early metastasis and hepatocellular carcinoma (HCC) recurrence within 1 month of surgery (n = 11), preoperative hepatic arterial chemoembolization (n = 5), death within 30 days of surgery due to liver failure (n = 6), or clinical evidence of infection or other inflammatory conditions before surgery (n = 15)
All patients were positive for hepatitis B surface antigens (HBsAg) and negative for anti-HCV. 281 (23.93%) patients were HBeAg positive, and the remaining 893 (76.07%) patients were negative for HBeAg
Summary
Inflammation has been regarded as the seventh symptom of cancer [1]. Increasing evidence has shown that systemic inflammatory response (SIR) may associate with poor cancerspecific outcomes [2]. The effect of SIR on carcinogenesis has been intensively studied. The presence of SIR can be determined using various markers, including c-reactive protein (CRP), absolute blood neutrophil or lymphocyte count and its ratios such as neutrophil-tolymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), and platelet to lymphocyte ratio (PLR). An elevation in PLR is another marker of inflammation, and has been proven to be relevant to poor clinical outcomes in different kinds of cancer patients, such as colorectal, esophageal and lung [5,6,7]
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