泛癌种中肌动蛋白相关蛋白 2/3 复合物亚基 5 的全面预后和免疫分析及在肝细胞癌中的鉴定。
A comprehensively prognostic and immunological analysis of actin-related protein 2/3 complex subunit 5 in pan-cancer and identification in hepatocellular carcinoma.
机构信息
Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Jiangxi Key Laboratory of Clinical and Translational Cancer Research, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
出版信息
Front Immunol. 2022 Sep 6;13:944898. doi: 10.3389/fimmu.2022.944898. eCollection 2022.
BACKGROUND
Actin-related protein 2/3 complex subunit 5 (ARPC5) is one of the members of actin-related protein 2/3 complex and plays an important role in cell migration and invasion. However, little is known about the expression pattern, prognosis value, and biological function of ARPC5 in pan-cancer. Thus, we focus on ARPC5 as cut point to explore a novel prognostic and immunological biomarker for cancers.
METHODS
The public databases, including TCGA, GTEx, and UCEC, were used to analyze ARPC5 expression in pan-cancer. The Human Protein Atlas website was applied to obtain the expression of ARPC5 in different tissues, cell lines, and single-cell types. Univariate Cox regression analysis and Kaplan-Meier analysis were used to explore the prognosis value of ARPC5 in various cancers. Spearman's correlation analysis was performed to investigate the association between ARPC5 expression and tumor microenvironment scores, immune cell infiltration, immune-related genes, TMB, MSI, RNA modification genes, DNA methyltransferases, and tumor stemness. Moreover, qPCR, Western blot, and immunohistochemistry were carried out to examine the differential expression of ARPC5 in HCC tissues and cell lines. CCK8, EdU, flow cytometry, wound-healing assays, and transwell assays were conducted to explore its role in tumor proliferation, apoptosis, migration, and invasion among HCC cells.
RESULTS
ARPC5 expression was upregulated in most cancer types and significantly associated with worse prognosis in KIRC, KIRP, LGG, and LIHC. mRNA expression of ARPC5 showed low tissue and cell specificity in normal tissues, cell lines, and single-cell types. ARPC5 expression was positively correlated with the tumor microenvironment scores, immune infiltrating cells, immune checkpoint-related genes in most cancers. ARPC5 in STAD and BRCA was positively associated with TMB, MSI, and neoantigens. We also discovered that ARPC5 was correlated with the expression of m1A-related genes, m5C-related genes, m6A-related genes, and DNA methyltransferases. In experiment analyses, we found that ARPC5 was significantly highly expressed in HCC tissues and HCC cells. Functionally, silencing ARPC5 dramatically decreased proliferation, migration, and invasion ability of HCC cells.
CONCLUSIONS
ARPC5 expression affects the prognosis of multiple tumors and is closely correlated to tumor immune infiltration and immunotherapy. Furthermore, ARPC5 may function as an oncogene and promote tumor progression in HCC.
背景
肌动蛋白相关蛋白 2/3 复合物亚基 5（ARPC5）是肌动蛋白相关蛋白 2/3 复合物的成员之一，在细胞迁移和侵袭中发挥重要作用。然而，关于 ARPC5 在泛癌中的表达模式、预后价值和生物学功能知之甚少。因此，我们关注 ARPC5 作为切点，探索癌症的新型预后和免疫生物标志物。
方法
使用 TCGA、GTEx 和 UCEC 等公共数据库分析泛癌中的 ARPC5 表达。应用人类蛋白质图谱网站获取 ARPC5 在不同组织、细胞系和单细胞类型中的表达。采用单因素 Cox 回归分析和 Kaplan-Meier 分析探讨 ARPC5 在各种癌症中的预后价值。采用 Spearman 相关性分析探讨 ARPC5 表达与肿瘤微环境评分、免疫细胞浸润、免疫相关基因、TMB、MSI、RNA 修饰基因、DNA 甲基转移酶和肿瘤干性的相关性。此外，通过 qPCR、Western blot 和免疫组化检测 HCC 组织和细胞系中 ARPC5 的差异表达。通过 CCK8、EdU、流式细胞术、划痕愈合实验和 Transwell 实验研究 ARPC5 在 HCC 细胞中的增殖、凋亡、迁移和侵袭中的作用。
结果
ARPC5 在大多数癌症类型中表达上调，在 KIRC、KIRP、LGG 和 LIHC 中与预后不良显著相关。正常组织、细胞系和单细胞类型中 ARPC5 的 mRNA 表达特异性低。在大多数癌症中，ARPC5 的表达与肿瘤微环境评分、免疫浸润细胞、免疫检查点相关基因呈正相关。STAD 和 BRCA 中的 ARPC5 与 TMB、MSI 和新抗原呈正相关。我们还发现 ARPC5 与 m1A 相关基因、m5C 相关基因、m6A 相关基因和 DNA 甲基转移酶的表达相关。在实验分析中，我们发现 ARPC5 在 HCC 组织和 HCC 细胞中表达显著上调。功能上，沉默 ARPC5 可显著降低 HCC 细胞的增殖、迁移和侵袭能力。
结论
ARPC5 的表达影响多种肿瘤的预后，与肿瘤免疫浸润和免疫治疗密切相关。此外，ARPC5 可能作为癌基因促进 HCC 中的肿瘤进展。
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