Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge.
Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge.
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肝细胞癌中血小板相关基因的遗传分析揭示了新的预后特征，并确定 PRKCD 作为潜在的分子桥梁
DOI：
10.1186/s12575-022-00185-9
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发表时间：
2022-12-03
影响因子：
6.4
通讯作者：
Yao, Wei
中科院分区：
文献类型：
--
作者：
Li, Xiangyu;Zhao, Kai;Lu, Yun;Wang, Jianming;Yao, Wei
肝细胞癌（Hepatocellular carcinoma，HCC）是一种典型的致死性胃肠道恶性肿瘤，由于其易复发、早期转移的侵袭性生物学特性，目前对其综合治疗仍是一个难题。血小板与肿瘤进展之间的密切联系已被广泛报道，血小板相关指标也被用于肿瘤的临床实践。本研究旨在探讨血小板相关基因在肝癌患者预后预测中的意义及其在肿瘤微环境中肝癌细胞和血小板之间的相互作用中的潜在作用。通过整合肝癌患者的RNA-seq数据和临床病理信息，我们基于单变量考克斯分析提取了血小板减少相关基因，并通过lasso考克斯回归分析进一步建立了相关的预后特征，并使用两个独立的肝癌队列作为外部验证。利用多种生物信息学方法来探索由风险模型分类的不同风险组之间的潜在功能差异。通过体外增殖、侵袭和迁移实验观察血小板刺激对肝癌细胞活力和运动能力的影响，并通过流式细胞术分析肝癌细胞对血小板活化的影响。开发了一种新的血小板相关风险模型，并根据中位风险评分将训练和测试队列中的患者分为不同的风险亚组。结果发现，高危状态与预后差和临床病理参数差密切相关。同时，免疫微环境构成的明显差异也表明不同的免疫状态可能是影响预后以及免疫治疗反应性的潜在决定因素。体外实验表明，PRKCD可作为肿瘤细胞与血小板之间的分子桥梁，参与肿瘤恶性表型的调控或介导血小板活化。简而言之，这项工作揭示了一种新的血小板相关风险特征，用于HCC患者的预后评估，并证实PRKCD是HCC细胞-血小板相互作用的关键信使，在介导血小板诱导的肿瘤进展中起着至关重要的作用。在线版本包含补充材料，可通过10.1186/s12575-022-00185-9获取。
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. The online version contains supplementary material available at 10.1186/s12575-022-00185-9.
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影响因子：
3.8
作者：
Hong YM;Yoon KT;Hwang TH;Cho M
通讯作者：
Cho M
影响因子：
3.8
作者：
通讯作者：
--
DOI：
10.18632/aging.101563
发表时间：
2018-09-21
期刊：
Aging
影响因子：
--
作者：
Lin T;Gu J;Qu K;Zhang X;Ma X;Miao R;Xiang X;Fu Y;Niu W;She J;Liu C
通讯作者：
Liu C
影响因子：
11.5
作者：
Lau, Chi Keung;Yang, Zhen Fan;Fan, Sheung Tat
通讯作者：
Fan, Sheung Tat
影响因子：
10.1
作者：
Carubbi, Cecilia;Masselli, Elena;Vitale, Marco
通讯作者：
Vitale, Marco