基于生物信息学分析评估肺鳞癌患者 HOXA11 水平及潜在分子通路的研究
Evaluation of the HOXA11 level in patients with lung squamous cancer and insights into potential molecular pathways via bioinformatics analysis.
机构信息
Department of Pathology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, 6 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
出版信息
World J Surg Oncol. 2018 Jun 18;16(1):109. doi: 10.1186/s12957-018-1375-9.
BACKGROUND
This study was carried out to discover the underlying role that HOXA11 plays in lung squamous cancer (LUSC) and uncover the potential corresponding molecular mechanisms and functions of HOXA11-related genes.
METHODS
Twenty-three clinical paired LUSC and non-LUSC samples were utilized to examine the level of HOXA11 using quantitative real-time polymerase chain reaction (qRT-PCR). The clinical significance of HOXA11 was systematically analyzed based on 475 LUSC and 18 non-cancerous adjacent tissues from The Cancer Genome Atlas (TCGA) database. A total of 102 LUSC tissues and 121 non-cancerous tissues were available from Oncomine to explore the expressing profiles of HOXA11 in LUSC. A meta-analysis was carried out to further assess the differential expression of HOXA11 in LUSC, including in-house qRT-PCR data, expressing data extracted from TCGA and Oncomine databases. Moreover, the enrichment analysis and potential pathway annotations of HOXA11 in LUSC were accomplished via Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of hub genes and according correlations with HOXA11 were assessed to further explore the biological role of HOXA11 in LUSC.
RESULTS
HOXA11 expression in LUSC had a tendency to be upregulated in comparison to adjacent non-cancerous tissues by qRT-PCR. TCGA data displayed that HOXA11 was remarkably over-expressed in LUSC compared with that in non-LUSC samples, and the area under curves (AUC) was 0.955 (P < 0.001). A total of 1523 co-expressed genes were sifted for further analysis. The most significant term enriched in the KEGG pathway was focal adhesion. Among the six hub genes of HOXA11, including PARVA, ILK, COL4A1, COL4A2, ITGB1, and ITGA5, five (with the exception of COL4A1) were significantly decreased compared with the normal lung tissues. Moreover, the expression of ILK was negatively related to HOXA11 (r = - 0.141, P = 0.002).
CONCLUSION
High HOXA11 expression may lead to carcinogenesis and the development of LUSC. Furthermore, co-expressed genes might affect the prognosis of LUSC.
背景
本研究旨在探究 HOXA11 在肺鳞癌（LUSC）中的潜在作用，并揭示其相关基因的潜在分子机制和功能。
方法
采用实时定量聚合酶链反应（qRT-PCR）检测 23 对临床配对的 LUSC 和非 LUSC 样本中 HOXA11 的水平。基于癌症基因组图谱（TCGA）数据库中 475 例 LUSC 和 18 例非癌旁组织，系统分析 HOXA11 的临床意义。从 Oncomine 数据库中获得 102 例 LUSC 组织和 121 例非癌组织，探讨 HOXA11 在 LUSC 中的表达谱。进行荟萃分析以进一步评估 HOXA11 在 LUSC 中的差异表达，包括内部 qRT-PCR 数据、从 TCGA 和 Oncomine 数据库中提取的表达数据。此外，通过基因肿瘤学（GO）和京都基因与基因组百科全书（KEGG）对 LUSC 中 HOXA11 的富集分析和潜在途径注释。评估关键基因的表达及其与 HOXA11 的相关性，以进一步探讨 HOXA11 在 LUSC 中的生物学作用。
结果
qRT-PCR 结果显示，与癌旁非癌组织相比，LUSC 中 HOXA11 的表达呈上调趋势。TCGA 数据显示，与非 LUSC 样本相比，LUSC 中 HOXA11 明显过表达，曲线下面积（AUC）为 0.955（P<0.001）。筛选出 1523 个共表达基因进行进一步分析。KEGG 途径中最显著的富集项为焦点黏附。在 HOXA11 的 6 个关键基因中，包括 PARVA、ILK、COL4A1、COL4A2、ITGB1 和 ITGA5，除 COL4A1 外，其余 5 个基因的表达均明显低于正常肺组织。此外，ILK 的表达与 HOXA11 呈负相关（r=-0.141，P=0.002）。
结论
高表达的 HOXA11 可能导致 LUSC 的发生和发展。此外，共表达基因可能影响 LUSC 的预后。
Zotero 插件