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Association between platelet count and hepatocellular carcinoma overall survival: a large retrospective cohort study.

ABSTRACT: OBJECTIVES:To explore the non-linear relationship between platelet count (PLT) and hepatocellular carcinoma (HCC) overall survival (OS). SETTING:The study was done in Sun Yat-sen University Cancer Center (SYSUCC) from January 2007 to May 2012, a total of 5005 consecutive participants at SYSUCC were retrospectively reviewed, and 979 patients with Barcelona clinic liver cancer (BCLC) stage B were selected for the final analysis. PARTICIPANTS:A total of 979 newly diagnosed patients with HCC with BCLC stage B were identified for the secondary analysis. Eight cases were excluded for missing data of PLT. MAIN OUTCOME MEASURES:Cox proportional hazard regression models were used to calculate multivariable-adjusted HRs and 95% CIs for HCC. The non-linear relationship was estimated through a restricted cubic spline regression, and a two-piecewise Cox proportional hazards model was further performed to calculate the threshold effect. We used multiple imputation to deal with the missing data. RESULTS:In the multivariate analysis, Log PLT was associated with a 91% risk increase in death (HR 1.91; 1.28 to 2.85) with adjustment for gender, Child-Pugh class, age × diameter of main tumour, both lobe with lesions × number of the intrahepatic lesions, alpha-fetoprotein (<25, ?25) and lactic dehydrogenase (<245, ?245). We also found a U-shape relationship between PLT and HCC OS at the inflexion point of 67.6×109/L. The HR was 0.12 (95% CI 0.03 to 0.52) for Log PLT?10.83?and 3.07 (CI 1.91 to 4.92) for Log PLT>10.83 after adjusting for potential confounders. The core results were consistent with those from the sensitivity analysis. Besides, a significantly higher hazard risk was found in the patients with age <55, both lobes with lesions, tumour diameter >50, haemoglobin ?120?and C reactive protein >10. CONCLUSION:PLT was nonlinearly associated with HCC OS.

SUBMITTER: Lu L

PROVIDER: S-EPMC7651714 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Association between platelet count and hepatocellular carcinoma overall survival: a large retrospective cohort study.

Lu Linbin L Su Zhimin Z Zheng Peichan P Wu Zhixian Z Zhang Yan Y He Huimin H Liu Jingnan J Lin Shan S Chen Xiong X

BMJ open 20201106 11

<h4>Objectives</h4>To explore the non-linear relationship between platelet count (PLT) and hepatocellular carcinoma (HCC) overall survival (OS).<h4>Setting</h4>The study was done in Sun Yat-sen University Cancer Center (SYSUCC) from January 2007 to May 2012, a total of 5005 consecutive participants at SYSUCC were retrospectively reviewed, and 979 patients with Barcelona clinic liver cancer (BCLC) stage B were selected for the final analysis.<h4>Participants</h4>A total of 979 newly diagnosed pat ...[more]

PMID: 33158820

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Project description:BackgroundPlatelets have been reported to influence tumor biology and may promote metastasis. Traditionally, thrombocytopenia, a hallmark of cirrhosis, was associated with hepatocellular carcinoma (HCC) development. However, the impact of platelet count on outcome in patients with established HCC is not well studied.MethodsOutcomes of patients with cirrhosis diagnosed with HCC between 1995 and 2013 (derivation cohort) and 2000-2016 (validation cohort) who were not eligible for surgical treatment and did not receive antiplatelet therapy were retrospectively studied. Thrombocytopenia was defined as platelet count < 150 g/L. High mean platelet volume (MPV) was defined as ≥median value of the respective cohort (derivation cohort: ≥11 fL; validation cohort: ≥10.6 fL).ResultsAmong 626 patients with unresectable HCC, thrombocytopenia was present in 378 (60.4%) and was associated with favorable baseline tumor characteristics: lower diameter of the largest nodule (5.6 ± 3.2 vs. 7.6 ± 4.2 cm), less extrahepatic spread (9.5 vs. 20.2%, both p < 0.001), less macrovascular invasion (21.2 vs. 31.0%, p = 0.005), and lower BCLC stages (63.0 vs. 73.4% BCLC C/D; p = 0.007) as compared to patients with normal platelet count. On univariate analysis, thrombocytopenia and larger MPV were associated with longer overall survival (OS) (thrombocytopenia: median OS [95% CI], 11.5 [9.3-13.8] vs. 5.5 [3.8-7.1] months; p = 0.001; MPV ≥11 fL: 11.7 [9.1-14.2] vs. 6.0 [4.4-7.6] months; p < 0.001). In multivariate analysis, the combined variable of thrombocytopenia and larger MPV was independently associated with longer OS (HR [95% CI], 0.80 [0.65-0.98]; p = 0.029). These results were confirmed in an independent external validation cohort of 525 patients with cirrhosis and HCC. Again, patients with thrombocytopenia and high MPV had significantly longer OS (15.3 [11.7-18.9] vs. 9.3 [7.4-11.2] months; p < 0.001).ConclusionsThrombocytopenia and higher MPV are associated with better outcome in patients with advanced HCC. These findings may prompt further clinical research on additive antiplatelet therapy in the prevention and management of HCC.

Project description:BackgroundHepatocellular carcinoma (HCC) is a major cause of cancer mortality and an increasing incidence worldwide; however, there are very few effective diagnostic approaches and prognostic biomarkers.Materials and methodsOne hundred forty-nine pairs of HCC samples from Gene Expression Omnibus (GEO) were obtained to screen differentially expressed genes (DEGs) between HCC and normal samples. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, Gene ontology enrichment analyses, and protein-protein interaction network were used. Cox proportional hazards regression analysis was used to identify significant prognostic DEGs, with which a gene expression signature prognostic prediction model was identified in The Cancer Genome Atlas (TCGA) project discovery cohort. The robustness of this panel was assessed in the GSE14520 cohort. We verified details of the gene expression level of the key molecules through TCGA, GEO, and qPCR and used immunohistochemistry for substantiation in HCC tissues. The methylation states of these genes were also explored.ResultsNinety-eight genes, consisting of 13 upregulated and 85 downregulated genes, were screened out in three datasets. KEGG and Gene ontology analysis for the DEGs revealed important biological features of each subtype. Protein-protein interaction network analysis was constructed, consisting of 64 nodes and 115 edges. A subset of four genes (SPINK1, TXNRD1, LCAT, and PZP) that formed a prognostic gene expression signature was established from TCGA and validated in GSE14520. Next, the expression details of the four genes were validated with TCGA, GEO, and clinical samples. The expression panels of the four genes were closely related to methylation states.ConclusionThis study identified a novel four-gene signature biomarker for predicting the prognosis of HCC. The biomarkers may also reveal molecular mechanisms underlying development of the disease and provide new insights into interventional strategies.

Dataset Information

Association between platelet count and hepatocellular carcinoma overall survival: a large retrospective cohort study.

Publications

Association between platelet count and hepatocellular carcinoma overall survival: a large retrospective cohort study.

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