Wu Hong-Mei, Huang Yuan-Yuan, Xu Yu-Qiu, Xiang Wei-Lai, Yang Chang, Liu Ru-Yuan, Li Di, Guo Xue-Feng, Zhang Zheng-Bao, Bei Chun-Hua, Tan Sheng-Kui, Zhu Xiao-Nian
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin 541199, Guangxi Zhuang Autonomous Region, China.
World J Gastrointest Oncol. 2024 Feb 15;16(2):475-492. doi: 10.4251/wjgo.v16.i2.475.
B56ε is a regulatory subunit of the serine/threonine protein phosphatase 2A, which is abnormally expressed in tumors and regulates various tumor cell functions. At present, the application of B56ε in pan-cancer lacks a comprehensive analysis, and its role and mechanism in hepatocellular carcinoma (HCC) are still unclear.
To analyze B56ε in pan-cancer, and explore its role and mechanism in HCC.
The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Profiling Interactive Analysis, and Tumor Immune Estimation Resource databases were used to analyze B56ε expression, prognostic mutations, somatic copy number alterations, and tumor immune characteristics in 33 tumors. The relationships between B56ε expression levels and drug sensitivity, immunotherapy, immune checkpoints, and human leukocyte antigen (HLA)-related genes were further analyzed. Gene Set Enrichment Analysis (GSEA) was performed to reveal the role of B56ε in HCC. The Cell Counting Kit-8, plate cloning, wound healing, and transwell assays were conducted to assess the effects of B56ε interference on the malignant behavior of HCC cells.
In most tumors, B56ε expression was upregulated, and high B56ε expression was a risk factor for adrenocortical cancer, HCC, pancreatic adenocarcinoma, and pheochromocytoma and paraganglioma (all < 0.05). B56ε expression levels were correlated with a variety of immune cells, such as T helper 17 cells, B cells, and macrophages. There was a positive correlation between B56ε expression levels with immune checkpoint genes and HLA-related genes (all < 0.05). The expression of B56ε was negatively correlated with the sensitivity of most chemotherapy drugs, but a small number showed a positive correlation (all < 0.05). GSEA analysis showed that B56ε expression was related to the cancer pathway, p53 downstream pathway, and interleukin-mediated signaling in HCC. Knockdown of B56ε expression in HCC cells inhibited the proliferation, migration, and invasion capacity of tumor cells.
B56ε is associated with the microenvironment, immune evasion, and immune cell infiltration of multiple tumors. B56ε plays an important role in HCC progression, supporting it as a prognostic marker and potential therapeutic target for HCC.
B56ε是丝氨酸/苏氨酸蛋白磷酸酶2A的一个调节亚基，在肿瘤中异常表达并调节多种肿瘤细胞功能。目前，B56ε在泛癌中的应用缺乏全面分析，其在肝细胞癌（HCC）中的作用及机制仍不清楚。
分析B56ε在泛癌中的情况，并探讨其在HCC中的作用及机制。
利用癌症基因组图谱、基因型-组织表达、基因表达谱交互分析和肿瘤免疫评估资源数据库，分析33种肿瘤中B56ε的表达、预后突变、体细胞拷贝数改变和肿瘤免疫特征。进一步分析B56ε表达水平与药物敏感性、免疫治疗、免疫检查点及人类白细胞抗原（HLA）相关基因之间的关系。进行基因集富集分析（GSEA）以揭示B56ε在HCC中的作用。采用细胞计数试剂盒-8、平板克隆、伤口愈合和Transwell实验评估B56ε干扰对HCC细胞恶性行为的影响。
在大多数肿瘤中，B56ε表达上调，高B56ε表达是肾上腺皮质癌、HCC、胰腺腺癌以及嗜铬细胞瘤和副神经节瘤的危险因素（均P<0.05）。B56ε表达水平与多种免疫细胞相关，如辅助性T细胞17、B细胞和巨噬细胞。B56ε表达水平与免疫检查点基因和HLA相关基因呈正相关（均P<0.05）。B56ε的表达与大多数化疗药物的敏感性呈负相关，但少数呈正相关（均P<0.05）。GSEA分析显示，B56ε表达与HCC中的癌症通路、p53下游通路和白细胞介素介导的信号传导相关。敲低HCC细胞中B56ε的表达可抑制肿瘤细胞的增殖、迁移和侵袭能力。
B56ε与多种肿瘤的微环境、免疫逃逸和免疫细胞浸润相关。B56ε在HCC进展中起重要作用，支持其作为HCC的预后标志物和潜在治疗靶点。
