基于生物信息学分析转录因子HLF及KLF7在头颈部鳞癌进展过程的表达及预后意义

Bioinformatics Analysis of the Expression and Prognostic Value of HLF and KLF7 in the Progression of Head and Neck Squamous Cell Carcinoma

目的:通过生物信息学手段筛选驱动头颈部鳞癌(HNSCC)进展的潜在关键转录因子,分析其表达特征及预后意义。方法:从癌症基因组图谱数据库获取HNSCC转录组测序数据,筛选不同分期肿瘤组织与正常黏膜组织的差异转录因子。通过STEM工具分析差异转录因子在HNSCC进展过程的表达模式。在R3.5.1环境下,利用survival包和survminer包计算差异转录因子的预后意义。最后利用人类蛋白图谱数据库对候选转录因子进行免疫组化验证,并通过基因集富集分析挖掘与转录因子密切相关的通路。结果:和正常组织相比,HNSCC各分期的差异转录因子分别为172(Ⅰ期),272(Ⅱ期),272(Ⅲ期),307(Ⅳ期),各分期共有差异转录因子为7个。其中HLF及KLF7等5个差异转录因子与HNSCC患者预后显著相关。免疫组化结果显示,上述转录因子表达趋势均与转录组测序结果一致,其中HLF在HNSCC 4个分期表达均显著下调,而KLF7则呈现相反趋势。基因集富集分析显示,HLF表达下调可显著激活细胞外基质分解及对Ⅰ型干扰素的反应等生物进程;KLF7高表达时,角质形成细胞增殖、细胞-基质连接组件等生物进程显著激活。结论:HLF及KLF7等转录因子表达失调与HNSCC分期及患者预后密切相关,并潜在参与驱动HNSCC的恶性进展。

Objective: To screen the potential key transcription factors driving the progression of head and neck squamous cell carcinoma( HNSCC) by bioinformatics analysis,and identify their expression characteristics and prognostic significance. Methods: The transcriptome sequencing data of HNSCC was obtained from the cancer genome Atlas( TCGA) database. The differentially expressed transcription factors( DE-TFs) between different tumor stages and normal mucosa were screened. The expression patterns of transcription factors throughout HNSCC progression were screened by STEM tool. Subsequently,prognostic significance of DE-TFs in patients with HNSCC was calculated by survival package and survminer package in R3.5.1. Finally,human protein atlas( HPA) database was used for the immunohistochemical verification of candidate transcription factors,and gene set enrichment analysis was performed to investigate the pathway closely related to the transcription factors. Results: Compared with that in the normal tissues,the DE-TFs in each stage of HNSCC was 172( Stage Ⅰ),272( Stage Ⅱ),272( Stage Ⅲ) and 307( Stage Ⅳ),respectively. A total of 7 DE-TFs were commonly shared by each tumor stage,among which five DE-TFs including HLF and KLF7 were significantly correlated with the prognosis of HNSCC patients. The immunohistochemical results showed that the expression manner of candidate TFs was consistent with the transcriptome sequencing data,among which HLF was significantly down-regulated in each stage of HNSCC,while KLF7 showed the opposite trend. Gene set enrichment analysis showed that down-regulation of HLF significantly activated biological processes( BP) including extracellular matrix disassembly and response to type Ⅰ interferon;when KLF7 was highly expressed,BP such as keratinocyte proliferation and cell substrate junction assembly were significantly activated. Conclusion: The dysregulation of transcription factors including HLF and KLF7 is closely related to the staging and prognosis of HNSCC patients,which may drive the malignant progression of HNSCC.