Wang Jing, Song Meng, Tang Jinming, Yue Haoran, Guo Xiaoyang, Chen Zhan, Shen Xiaolan, Cao Mingbo
Department of Gastroenterology, People's Hospital of Zhengzhou University, Henan Provincial People's Hospital, Zhengzhou, China.
Henan Provincial International Coalition Laboratory of Oncology Precision Treatment, People's Hospital of Zhengzhou University, Zhengzhou, China.
Front Med (Lausanne). 2025 Mar 10;12:1513233. doi: 10.3389/fmed.2025.1513233. eCollection 2025.
Hepatocellular carcinoma (HCC) is the third most prevalent cause of cancer-related mortality globally and the sixth most common cancer overall. It is critical to investigate new biomarkers and prognostic variables because there are currently no early diagnostic indicators. Actin-related proteins (ARPs) are involved in transcriptional regulation, chromatin remodeling, and DNA repair-all processes that have been connected to the development of cancer. However, it's still unclear how ARPs and HCC are related.
Through the examination of databases like The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC), we examined the variations in the expression of ARPs between the transcriptomes of normal tissue and HCC. Furthermore, univariate and multivariate Cox analysis were used to assess the prognostic effects of ARPs. The investigation of immune cell infiltration and possible functional enrichment followed. Additionally, tissue chips containing regional liver cancer specimens were used to confirm ACTR6 expression and the clinical impact of prognosis using an immunohistochemistry (IHC) test. Finally, to investigate the expression and function of ACTR6 in liver cancer cells, real-time qPCR (RT-qPCR) assays, CCK-8, clone creation, cell cycle, and transwell migration and invasion experiments were carried out.
We found that, in addition to ACTR3C, 17 ARPs were significantly overexpressed in HCC compared with normal tissues. In both univariate and multivariate Cox models, ACTR6 and ACTL6A were identified as potential independent risk factors for the prognosis of HCC, with ACTR6 having the lowest -value. Clinical samples also confirmed this conclusion. Furthermore, ACTR6 overexpression showed a strong connection with immune cell infiltration levels and clinical and pathological factors linked to a poor prognosis. Functionally, knocking down ACTR6 inhibited cell migration and proliferation, produced a G1 cell cycle arrest, and decreased the viability of liver cancer cells.
These findings demonstrate that ACTR6 is highly expressed in HCC and is associated with poor prognosis. In addition, ACTR6 may induce immune cell infiltration and promote hepatocarcinogenesis by regulating the cell cycle.
肝细胞癌（HCC）是全球癌症相关死亡的第三大常见原因，也是总体上第六大常见癌症。由于目前尚无早期诊断指标，研究新的生物标志物和预后变量至关重要。肌动蛋白相关蛋白（ARPs）参与转录调控、染色质重塑和DNA修复，所有这些过程都与癌症的发生发展有关。然而，ARPs与HCC之间的关系仍不清楚。
通过检查如癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）等数据库，我们研究了正常组织和HCC转录组之间ARPs表达的差异。此外，使用单变量和多变量Cox分析来评估ARPs的预后影响。随后进行了免疫细胞浸润和可能的功能富集研究。此外，使用含有局部肝癌标本的组织芯片通过免疫组织化学（IHC）测试来确认ACTR6表达及其对预后的临床影响。最后，为了研究ACTR6在肝癌细胞中的表达和功能，进行了实时定量PCR（RT-qPCR）分析、CCK-8、克隆创建、细胞周期以及Transwell迁移和侵袭实验。
我们发现，除了ACTR3C外，与正常组织相比，17种ARPs在HCC中显著过表达。在单变量和多变量Cox模型中，ACTR6和ACTL6A被确定为HCC预后的潜在独立危险因素，其中ACTR6的风险值最低。临床样本也证实了这一结论。此外，ACTR6过表达与免疫细胞浸润水平以及与预后不良相关的临床和病理因素密切相关。在功能上，敲低ACTR6可抑制细胞迁移和增殖，导致G1期细胞周期停滞，并降低肝癌细胞的活力。
这些发现表明ACTR6在HCC中高表达且与预后不良相关。此外，ACTR6可能通过调节细胞周期诱导免疫细胞浸润并促进肝癌发生。
