Deng Yun, He Rongquan, Zhang Rui, Gan Binliang, Zhang Yu, Chen Gang, Hu Xiaohua
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
Oncol Lett. 2018 Jun;15(6):8556-8572. doi: 10.3892/ol.2018.8381. Epub 2018 Mar 29.
Previous studies have investigated the association between HOXA13 and non-small cell lung cancer. However, the role of HOXA13 expression in the occurrence and progression of lung adenocarcinoma (LUAD) has not yet been investigated. In the present study, HOXA13-related data mining of The Cancer Genome Atlas (TCGA), polymerase chain reaction (PCR) data from our cases and the case information in Oncomine was conducted for validation. The expression data of HOXA13 in lung cancer cell lines were also collected from the Cancer Cell Line Encyclopedia (CCLE) database for further verification. A comprehensive meta-analysis of the expression of HOXA13 was also performed, integrating the data of TCGA, in-house PCR and Oncomine. Genes that were co-expressed with HOXA13 were subsequently identified through cBioPortal and Multi Experiment Matrix (MEM), and the potential role and mechanism of HOXA13 in LUAD was investigated. The expression value of HOXA13 in the LUAD group, which comprised 237 cases, was 3.74±2.694, significantly higher than its expression value in the non-cancerous group (0.92±0.608, P<0.001). The pooled SMD for HOXA13 was 0.346 (95% CI, 0.052-0.640; P=0.068; I2=51.3%; P=0.021), The meta-analysis of diagnostic tests revealed that the area under the summary receiver operating characteristic curve (SROC) was 0.78 (95% CI, 0.75-0.82). The results demonstrated that HOXA13 is highly expressed in LUAD. In addition to the studies on HOXA13 expression in tissues, the expression data of HOXA13 in lung cancer cell lines were also collected from the CCLE database for further verification of these conclusions. Genes that were co-expressed with HOXA13 were identified for pathway analysis. The most enriched Gene Ontology terms in the genes co-expressed with HOXA13 were positive regulation of transcription from RNA polymerase II promoter, signal transduction and positive regulation of GTPase activity in biological process; cytoplasm, integral component of membrane and plasma membrane in cellular component; and significantly involved in protein binding, transcription factor activity, sequence-specific DNA binding and sequence-specific DNA binding in molecular function. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these target genes were clearly involved in Pathways in cancer, Proteoglycans in cancer and cAMP signaling pathway. The hub genes obtained from the four protein-protein interaction networks were associated with HOXA13. The results of the bioinformatics research in the present study revealed that HOXA13 may influence the expression of these hub genes in such a way as to promote the occurrence and development of LUAD. In conclusion, the expression of HOXA13 in patients with LUAD and its potential clinical value were analyzed comprehensively in the present study using data from a variety of sources. Through bioinformatics analysis, evidence that HOXA13 may promote the occurrence and development of LUAD was obtained.
以往的研究调查了HOXA13与非小细胞肺癌之间的关联。然而,HOXA13表达在肺腺癌(LUAD)发生和进展中的作用尚未得到研究。在本研究中,对癌症基因组图谱(TCGA)中与HOXA13相关的数据挖掘、我们病例的聚合酶链反应(PCR)数据以及Oncomine中的病例信息进行了验证。还从癌细胞系百科全书(CCLE)数据库收集了肺癌细胞系中HOXA13的表达数据以作进一步验证。还对HOXA13的表达进行了全面的荟萃分析,整合了TCGA、内部PCR和Oncomine的数据。随后通过cBioPortal和多实验矩阵(MEM)鉴定了与HOXA13共表达的基因,并研究了HOXA13在LUAD中的潜在作用和机制。LUAD组(共237例)中HOXA13的表达值为3.74±2.694,显著高于其在非癌组中的表达值(0.92±0.608,P<0.001)。HOXA13的合并标准化均值差(SMD)为0.346(95%置信区间,0.052 - 0.640;P = 0.068;I2 = 51.3%;P = 0.021),诊断试验的荟萃分析显示,汇总受试者工作特征曲线(SROC)下的面积为0.78(95%置信区间,0.75 - 0.82)。结果表明HOXA13在LUAD中高表达。除了对HOXA13在组织中的表达进行研究外,还从CCLE数据库收集了肺癌细胞系中HOXA13的表达数据以进一步验证这些结论。鉴定了与HOXA13共表达的基因用于通路分析。与HOXA13共表达的基因中最富集的基因本体学术语在生物学过程中为RNA聚合酶II启动子转录正调控、信号转导和GTPase活性正调控;在细胞组分中为细胞质、膜整合成分和质膜;在分子功能中显著涉及蛋白质结合、转录因子活性、序列特异性DNA结合和序列特异性DNA结合。京都基因与基因组百科全书分析显示,这些靶基因明显参与癌症通路、癌症中的蛋白聚糖和cAMP信号通路。从四个蛋白质 - 蛋白质相互作用网络获得的枢纽基因与HOXA13相关。本研究的生物信息学研究结果表明,HOXA13可能通过影响这些枢纽基因的表达来促进LUAD的发生和发展。总之,本研究使用来自多种来源的数据全面分析了HOXA13在LUAD患者中的表达及其潜在临床价值。通过生物信息学分析,获得了HOXA¡3可能促进LUAD发生和发展的证据。