Dataset Information

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

ABSTRACT: Purpose: Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth stimulatory effect on several types of carcinoma and tumor cells. Since a large portion of 5-HT is stored and transported by platelets, the aim of this study was to assess the influence of platelet-sequestered 5-HT on post-resection hepatocellular carcinoma (HCC) recurrence. Methods: This pilot study was conducted in a cohort of forty patients diagnosed with HCC undergoing partial hepatectomy. 5-HT levels in serum, plasma and intra-platelet (IP) were monitored preoperatively and four weeks after liver resection. The patients were followed every three months after the surgery. Results: Follow-up was standardized to a fixed length of time. Fifteen patients (37.5%) developed HCC recurrence during 18 months follow-up. Patients with recurrence had significantly reduced serum and IP 5-HT levels at four weeks of liver resection (P = 0.003 and P = 0.014 respectively). Accordingly, in the Cox regression hazard model, serum and IP 5-HT were able to independently predict the recurrence (hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.75 and hazard ratio = 0.1, 95% confidence interval = 0.01 - 0.89 respectively). The optimal cut-off value of 42.77 ng/ml for serum [area under the curve (AUC): 0.78, P = 0.003] and 0.3117 ng per 106 platelets (AUC: 0.733, P = 0.015), on receiver operating characteristic (ROC) curve corresponded to maximum sensitivity and specificity of prediction. The disease free interval was significantly worse in patients with low serum and IP 5-HT (P = 0.001 and P = 0.029 respectively). Conclusion: IP 5-HT monitored during early follow-up, after liver resection may represent a useful marker of early HCC recurrence.

SUBMITTER: Aryal B

PROVIDER: S-EPMC5706000 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

Aryal Bibek B Shimizu Toshiaki T Kadono Jun J Furoi Akira A Komokata Teruo T Kitazono Iwao I Koriyama Chihaya C Yamakuchi Munekazu M Hashiguchi Teruto T Imoto Yutaka Y

Journal of Cancer 20171023 19

<b>Purpose:</b> Serotonin (5-hydroxytryptamine, 5-HT) is well known for its growth stimulatory effect on several types of carcinoma and tumor cells. Since a large portion of 5-HT is stored and transported by platelets, the aim of this study was to assess the influence of platelet-sequestered 5-HT on post-resection hepatocellular carcinoma (HCC) recurrence. <b>Methods</b>: This pilot study was conducted in a cohort of forty patients diagnosed with HCC undergoing partial hepatectomy. 5-HT levels i ...[more]

PMID: 29187873

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Project description:BackgroundEarly recurrence of hepatocellular carcinoma (HCC) is a major obstacle to improving the prognosis, and no widely accepted adjuvant therapy guideline for patients post-liver resection is available. Currently, all available methods and biomarkers are insufficient to accurately predict post-operation HCC patients' risk of early recurrence and their response to adjuvant therapy.MethodsIn this study, we downloaded four gene expression datasets (GSE14520, GSE54236, GSE87630, and GSE109211) from the Gene Expression Omnibus database and identified 34 common differentially expressed genes associated with HCC dysregulation and response to adjuvant sorafenib. Then, we constructed a novel 11-messenger RNA predictive model by using ROC curves analysis, univariate Cox regression analysis, and LASSO Cox regression analysis. Furthermore, we validated the predictive values of the risk model in GSE14520 and TCGA-LIHC cohorts by using Kaplan-Meier survival analysis, multivariable Cox regression analysis, and decision curve analysis, respectively.ResultsThe risk score model could identify patients with a high risk of HCC recurrence at the early stage and could predict the response of patients to adjuvant sorafenib. Patients with a high risk score had a worse recurrence rate in training cohorts (2-year: p < 0.0001, hazard ratio (HR): 4.658, confidence interval 95% CI [2.895-7.495]; 5-year: p < 0.0001, HR: 3.251, 95% CI [2.155-4.904]) and external validation cohorts (2-year: p < 0.001, HR: 3.65, 95% CI [2.001-6.658]; 5-year: p < 0.001, HR: 3.156, 95% CI [1.78-5.596]). The AUC values of the risk score model for predicting tumor early recurrence were 0.746 and 0.618, and that of the risk score model for predicting the response to adjuvant sorafenib were 0.722 and 0.708 in the different cohort, respectively. Multivariable Cox regression analysis and decision curve analysis also showed that the risk score model was superior to and independent of other clinicopathologic characteristics. Moreover, the risk score model had excellent abilities to predict the overall survival and HCC recurrence of patients with the same tumor stage category.ConclusionsOur risk model is a reliable and superior predictive tool. With this model, we could optimize the risk stratification based on early tumor recurrence and could evaluate the response of patients to adjuvant sorafenib after liver resection.

Dataset Information

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

Publications

Post-Resection Exhaustion of Intra-Platelet Serotonin: Also an Indicator of Early Hepatocellular Carcinoma Recurrence?

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