Zhao Huan, Wang Yu, Yang Zhishi, Wei Wenxin, Cong Zhuangzhi, Xie Yanting
Department of General Surgery, Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
Department of Hepatobiliary Surgery, Third Affiliated Hospital of Naval Military Medical University, Shanghai, China.
Ann Transl Med. 2022 Nov;10(21):1168. doi: 10.21037/atm-22-4798.
Currently, the only broadly used biomarker for hepatocellular carcinoma (HCC), alpha fetoprotein (AFP), has multiple limitations and the need for novel biomarkers is urgent. Aurora kinase B (AURKB) is a key mitotic protein kinase which performs a critical function in cell cycle progression. Nonetheless, neither the function nor the mechanism of AURKB in HCC following curative surgery is fully grasped at this time. This study sought to evaluate the impact of AURKB on prognosis and the tumor immune microenvironment (TIME) in HCC.
We evaluated both the expression profile of AURKB in HCC and its clinical value using online databases and clinical specimens. The prognostic value of AURKB was studied by Kaplan-Meier survival analysis, and the link between AURKB and tumor-infiltrating immune cells (TIICs) were analyzed.
We found the mRNA expression patterns of AURKB were remarkably upregulated in HCC in contrast with adjoining normal tissues (P<0.001). Upregulation of the AURKB protein in HCC was additionally verified by clinical samples. The expression of AURKB was substantially associated with Child-Pugh, microvascular invasion (MVI), Edmondson-Steiner grade, and tumor recurrence. Furthermore, patients diagnosed with HCC who had a low AURKB expression had a better. Our data suggested age [hazard ratio (HR): 1.34], alanine aminotransferase (ALT) (HR: 1.65), tumor size (HR: 1.99), mor number (HR: 1.60), MVI (HR: 1.93), grade (HR: 5.58), and AURKB expression (HR: 3.63) independently functioned as prognostic risk indicators for HCC (P<0.05). Importantly, we also found AURKB expression was inversely linked to resting natural killer (NK) cells, M2 macrophages, activated mast cells, and naive B cells, and positively linked to M0 macrophages, T follicular helper cells (Tfh), regulatory T cells (Treg), and resting myeloid dendritic cells. In addition, AURKB expression was also positively linked to the immune checkpoints of PDCD1, CD274, CTLA4, and LAG3. Finally, 1,696 DEGs were discovered, and were predominantly implicated in chromosome segregation, cell cycle, xenobiotic metabolic process, calcium signaling pathway, bile secretion, tyrosine metabolism, and DNA replication.
AURKB may be a potential prognostic biomarker for HCC after curative surgery, which correlates with MVI and the TIME in HCC.
目前，肝细胞癌（HCC）唯一广泛使用的生物标志物甲胎蛋白（AFP）有多种局限性，因此迫切需要新的生物标志物。极光激酶B（AURKB）是一种关键的有丝分裂蛋白激酶，在细胞周期进程中发挥着关键作用。然而，目前对于根治性手术后AURKB在HCC中的功能和机制尚未完全了解。本研究旨在评估AURKB对HCC预后和肿瘤免疫微环境（TIME）的影响。
我们使用在线数据库和临床标本评估了AURKB在HCC中的表达谱及其临床价值。通过Kaplan-Meier生存分析研究AURKB的预后价值，并分析AURKB与肿瘤浸润免疫细胞（TIIC）之间的联系。
我们发现与相邻正常组织相比，HCC中AURKB的mRNA表达模式显著上调（P<0.001）。临床样本进一步证实了HCC中AURKB蛋白的上调。AURKB的表达与Child-Pugh分级、微血管侵犯（MVI）、Edmondson-Steiner分级和肿瘤复发密切相关。此外，AURKB表达低的HCC患者预后较好。我们的数据表明年龄[风险比（HR）：1.34]、丙氨酸转氨酶（ALT）（HR：1.65）、肿瘤大小（HR：1.99）、肿瘤数量（HR：1.60）、MVI（HR：1.93）、分级（HR：5.58）和AURKB表达（HR：3.63）独立作为HCC的预后风险指标（P<0.05）。重要的是，我们还发现AURKB表达与静息自然杀伤（NK）细胞、M2巨噬细胞、活化肥大细胞和幼稚B细胞呈负相关，与M0巨噬细胞、滤泡辅助性T细胞（Tfh）、调节性T细胞（Treg）和静息髓样树突状细胞呈正相关。此外，AURKB表达还与PDCD1、CD274、CTLA4和LAG3的免疫检查点呈正相关。最后，发现了1696个差异表达基因（DEG），主要涉及染色体分离、细胞周期、异生物质代谢过程、钙信号通路、胆汁分泌、酪氨酸代谢和DNA复制。
AURKB可能是根治性手术后HCC的潜在预后生物标志物，它与HCC中的MVI和TIME相关。
