Objective Platelets are the mammals-specified component of blood that initiates a blood clot,of which the major function is to participate to hemostasis,by adhesion,activation,and aggregation.Cumulating evidences indicate that platelets have an important role in progression and metastasis of cancers through various mechanisms,such as promotion of epithelial-to-mesenchymal transition and angiogenesis,and cancer cell protection from immune surveillance.In addition,several recent clinical researches reported that platelet is a prognostic predictor in various cancers,including prostate,rectal,lung,pancreatic,ovarian,renal,breast,gastric,bladder,and liver cancers.Up to date,only a few studies explored impact of platelets,including composed types(such as platelets-to-lymphocyte ratio),on prognosis of ICC.So we need to confirm the impact of platelet levels on outcomes of intrahepatic cholangiocarcinoma(ICC).Methods 112 patients who underwent hepatic resection with curative intent between Nov 2011 to Jul 2013 from Eastern Hepatobiliary Surgery Hospital(Shanghai,China)and 106 patients between Jan 2007 to Jul 2015 from Renji Hospital(Shanghai,China)were enrolled and their tissue arrays were studied.Tumoral platelet levels were evaluated by immunohistochemistry of CD41.Prognostic cut-off ranges were testified by stratifying according to the median,interquartile,and proportion of survivals.Clinical factors,such as Age,gender,liver fluke,liver cirrhosis,hepatitis B virus(HBV)infection,and hepatitis C virus(HCV)infection et al,associated with platelet were identified using the Spearmans correlation test.Splenic injection of HCCC-9810 cells was performed in aspirin and saline groups of nude mice to evaluate impact of platelet reduction on development of ICC.Bioinformatics,including GO(Gene Ontology),KEGG(Kyoto Encyclopedia of Genes and Genomes),and protein-protein interactions(PPI)analyses were performed using the STRING database(version 11.0; https://stringdb.org/).[25] All statistical analyses were performed using the SPSS(version 22.0; Chicago,IL)and the R project for statistical computing(version 3.5.2; https://www.r-project.org/).Results Serum platelet count was not an independent prognostic factor,whereas tumoral platelet expression was found to be an independent predictor for both relapse-free survival(hazard ratio [HR],1.625; 95%confidence interval [CI],1.038-2.544; P=0.034)and overall survival(HR,1.691; 95%CI,1.084-2.636; P=0.020).Serum and tumoral platelet showed no significant association(P=0.194).Serum carbohydrate antigen 125 and 242,and early recurrence were correlated with tumoral platelet level.Platelet reduction by aspirin treatment significantly inhibited liver metastasis of ICC cells,and expressions of CD41 and c-Myc.Bioinformatical analyses indicated significant association between CD41 network and cancer-associated pathways,such as PI3K-Akt and Rap1 signaling pathways.Conclusions High platelet level predicts unfavorable prognosis of ICC after surgical resection.Among the platelet levels,tumoral platelet is an independent prognostic factor.In addition,tumoral platelet is significantly predictive of survival in most patients and subgroups.Platelet reduction by aspirin treatment deleted tumoral platelet levels and seems to inhibit the development of ICC.CD41-associated networkassociated genes,biological processes,molecular functions,cellular components,and KEGG pathways may be supportive in future studies exploring experimental impact of tumoral platelet on outcomes of ICC.In our concern,it is the time to consider implementation of low-dose aspirin use to prevent incidence and recurrence of ICC after resection,which awaits future clinical trials.