肝细胞癌（HCC）属于具有代表性的致死性消化系统恶性肿瘤，由于其易于复发和早期转移的侵袭性生物学特征，HCC的综合管理目前仍然难以解决。血小板与肿瘤进展之间的密切关联已得到广泛报道，血小板相关指标也在癌症的临床实践中使用。本研究旨在调查血小板相关基因在HCC患者预后预测中的意义，以及它们在肿瘤微环境中的HCC细胞与血小板交流中的潜在作用。通过整合HCC患者的RNA-seq数据和临床病理学信息，我们基于单变量Cox分析提取了预后相关的血小板相关基因，并进一步通过Lasso Cox回归分析建立了相关的预后标志，并使用两个独立的HCC队列进行外部验证。多种生物信息学方法被用于探索不同风险组之间的潜在功能差异。并进行了体外增殖、侵袭和迁移实验，以研究血小板刺激对HCC细胞的生存力和运动性的影响，流式细胞术分析用于证明HCC细胞对血小板激活的影响。本研究发现了一种新的与血小板相关的风险模型，根据中位数风险得分将训练和测试队列中的患者分为不同的风险亚组。观察到高风险状态与恶劣预后和更差的临床病理参数密切相关。同时，免疫微环境的明显差异也表明不同的免疫状态可能是影响预后和免疫治疗反应性的潜在决定因素。此外，体外实验表明，PRKCD可作为肿瘤细胞和血小板之间的分子桥梁，参与调节肿瘤恶性表型或介导血小板激活。总之，这项研究揭示了一种新的与血小板相关的风险标志物，用于评估HCC患者的预后，并证实PRKCD是HCC细胞血小板相互作用的关键信使，并对介导血小板诱导的肿瘤进展起至关重要的作用。© 2022。作者（们）。

Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment.By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells' viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation.A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation.In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.© 2022. The Author(s).