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Abstract：
Liver hepatocellular carcinoma (LIHC) is one of the most common liver malignancies with high mortality and morbidity. Thus, it is crucial to identify potential biomarker that is capable of accurately predicting the prognosis and therapeutic response of LIHC. Kinesin family member 5A (KIF5A) is a microtubule-based motor protein involved in the transport of macromolecules such as organelle proteins in cells. Recent studies have illustrated that the high expression of KIF5A was related to poor prognosis of solid tumors, including bladder cancer, prostate cancer, and breast cancer. However, little is currently known concerning the clinical significance of KIF5A expression in LIHC. Herein, by adopting multi-omics bioinformatics analysis, we comprehensively uncovered the potential function and the predictive value of KIF5A in stratifying clinical features among patients with LIHC, for which a high KIF5A level predicted an unfavorable clinical outcome. Results from KIF5A-related network and enrichment analyses illustrated that KIF5A might involve in microtubule-based process, antigen processing and presentation of exogenous peptide antigen via MHC class II. Furthermore, immune infiltration and immune function analyses revealed upregulated KIF5A could predict a unique tumor microenvironment with more CD8+T cells and a higher level of anti-tumor immune response. Evidence provided by immunohistochemistry staining (IHC) further validated our findings at the protein level. Taken together, KIF5A might serve as a novel prognostic biomarker for predicting immunotherapy response and could be a potential target for anti-cancer strategies for LIHC.
摘要：
肝细胞肝癌(LIHC)是最常见的肝脏恶性肿瘤之一,具有较高的死亡率和发病率。因此，确定能够准确预测LIHC预后和治疗反应的潜在生物标志物至关重要.驱动蛋白家族成员5A（KIF5A）是一种基于微管的运动蛋白，参与大分子如细胞器蛋白在细胞中的运输。最近的研究表明,KIF5A的高表达与实体瘤的不良预后有关。包括膀胱癌,前列腺癌,和乳腺癌。然而,目前对LIHC中KIF5A表达的临床意义知之甚少。在这里，通过采用多组学生物信息学分析，我们全面揭示了KIF5A在LIHC患者临床特征分层中的潜在功能和预测价值，高KIF5A水平预测不利的临床结果。KIF5A相关网络和富集分析的结果表明，KIF5A可能参与基于微管的过程，抗原加工和通过MHCII类呈递外源肽抗原。此外，免疫浸润和免疫功能分析表明,上调的KIF5A可以预测具有更多CD8+T细胞和更高水平抗肿瘤免疫应答的独特肿瘤微环境.免疫组织化学染色（IHC）提供的证据进一步验证了我们在蛋白质水平上的发现。一起来看,KIF5A可能作为预测免疫治疗反应的新型预后生物标志物，并且可能成为LIHC抗癌策略的潜在靶标。
