Ma Chenxi, Kang Wenyan, Yu Lu, Yang Zongcheng, Ding Tian
Department of Periodontology, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University and Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.
Front Oncol. 2020 Dec 9;10:590006. doi: 10.3389/fonc.2020.590006. eCollection 2020.
AUNIP, a novel prognostic biomarker, has been shown to be associated with stromal and immune scores in oral squamous cell carcinoma (OSCC). Nonetheless, its role in other cancer types was unclear. In this study, AUNIP expression was increased in hepatocellular carcinoma (HCC) and lung adenocarcinoma (LUAD) according to data from The Cancer Genome Atlas (TCGA) database, Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), and Gene Expression Omnibus (GEO) database (GSE45436, GSE102079, GSE10072, GSE31210, and GSE43458). Further, according to copy number variation analysis, AUNIP up-regulation may be associated with copy number variation. Immunohistochemistry showed AUNIP expression was higher in HCC and LUAD compared with the normal tissues. Receiver operating characteristic (ROC) curve analysis demonstrated that AUNIP is a candidate diagnostic biomarker for HCC and LUAD. Next, TCGA, International Cancer Genome Consortium (ICGC), and GEO (GSE31210 and GSE50081) data showed that increased AUNIP expression clearly predicted poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HCC and LUAD. Additionally, multivariate Cox regression analysis involving various clinical factors showed that AUNIP is an independent prognostic biomarker for HCC and LUAD. Next, the role of AUNIP in HCC and LUAD was explored via a co-expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and a gene set variation analysis (GSVA). HCC and LUAD exhibited almost identical enrichment results. More specifically, high AUNIP expression was associated with DNA replication, cell cycle, oocyte meiosis, homologous recombination, mismatch repair, the p53 signal transduction pathway, and progesterone-mediated oocyte maturation. Lastly, the Tumor Immune Estimation Resource (TIMER) tool was used to determine the correlations of AUNIP expression with tumor immune infiltration. AUNIP expression was positively correlated with the infiltration degree of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in HCC. However, AUNIP expression was negatively correlated with the infiltration degree of B cells, CD4+ T cells, and macrophages in LUAD. In addition, AUNIP expression was correlated with immune infiltration in various other tumors. In conclusion, AUNIP, which is associated with tumor immune infiltration, is a candidate diagnostic and prognostic biomarker for HCC and LUAD.
AUNIP是一种新型的预后生物标志物，已被证明与口腔鳞状细胞癌（OSCC）的基质和免疫评分相关。然而，其在其他癌症类型中的作用尚不清楚。在本研究中，根据癌症基因组图谱（TCGA）数据库、肝细胞癌综合分子数据库（HCCDB）和基因表达综合数据库（GEO）（GSE45436、GSE102079、GSE10072、GSE31210和GSE43458）的数据，肝细胞癌（HCC）和肺腺癌（LUAD）中AUNIP的表达增加。此外，根据拷贝数变异分析，AUNIP上调可能与拷贝数变异有关。免疫组织化学显示，与正常组织相比，HCC和LUAD中AUNIP的表达更高。受试者工作特征（ROC）曲线分析表明，AUNIP是HCC和LUAD的候选诊断生物标志物。接下来，TCGA、国际癌症基因组联盟（ICGC）和GEO（GSE31210和GSE50081）的数据显示，AUNIP表达增加清楚地预示着HCC和LUAD患者的总生存期（OS）、疾病特异性生存期（DSS）和无进展生存期（PFI）较差。此外，涉及各种临床因素的多变量Cox回归分析表明，AUNIP是HCC和LUAD的独立预后生物标志物。接下来，通过共表达分析、基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析以及基因集变异分析（GSVA）探索了AUNIP在HCC和LUAD中的作用。HCC和LUAD表现出几乎相同的富集结果。更具体地说，高AUNIP表达与DNA复制、细胞周期、卵母细胞减数分裂、同源重组、错配修复、p53信号转导通路和孕酮介导的卵母细胞成熟有关。最后，使用肿瘤免疫评估资源（TIMER）工具确定AUNIP表达与肿瘤免疫浸润的相关性。AUNIP表达与HCC中B细胞、CD4+T细胞、CD8+T细胞、中性粒细胞、巨噬细胞和树突状细胞的浸润程度呈正相关。然而，AUNIP表达与LUAD中B细胞、CD4+T细胞和巨噬细胞的浸润程度呈负相关。此外，AUNIP表达与其他各种肿瘤中的免疫浸润相关。总之，与肿瘤免疫浸润相关的AUNIP是HCC和LUAD的候选诊断和预后生物标志物。
