Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2020, Vol. 34 ›› Issue (4): 117-124.doi: 10.6040/j.issn.1673-3770.0.2020.189

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Analysis of differentially expressed genes during cetuximab treatment of head and neck squamous cell carcinoma using bioinformaticsYU Kena1, SUN Kaiyue2, ZHANG Jie1, JIN Peng1 1. Department of Otorhinolaryngology & Head and Neck Surgery, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; 2. Shandong Provincial Otorhinolaryngology Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250022, Shandong, ChinaAbstract:

ObjectiveThe aim of this study was to provide new perspectives and targets for the treatment of HNSCC by screening differentially expressed genes during cetuximab treatment of head and neck squamous cell carcinoma(HNSCC)using bioinformatics. MethodsThe chip dataset, GSE109756, was downloaded from the GEO database, and the online analysis tool, GEO2R, was used to screen differentially expressed genes in head and neck squamous cell carcinoma tissues treated with and without cetuximab. The DAVID 6.8 and STRING online software were used to analyze the function of the differentially expressed genes, their pathway enrichment, and their protein interactions. Cytoscape was used to visualize and analyze the protein interactions. The online analysis tool, X2K, was used to find the transcription factors, the kinases of differentially expressed genes, and their mutual regulatory relationship with the targeted genes. ResultsNinety-one differentially expressed genes, including 50 up-regulated and 41 down-regulated genes(P<0.05; | logFC | > 1), were found in head and neck squamous cell carcinoma tissues treated with and without cetuximab. The GO and KEGG pathway analyses suggested that these differentially expressed genes were mainly enriched with immunomodulation, extracellular matrix, and other processes. Through the construction of a protein-protein interaction network, we screened CD163, VSIG4, and 3 other core differentially expressed genes(P<0.05), which were up-regulated after cetuximab treatment. In addition, our analysis shows that transcription factors, including SUZ12, TP63, and ESR1, played a key role in cetuximab treatment(P<0.05)and MAPK14, CDK1, and MAPK1 were the most important kinases during the process(P<0.05). ConclusionCD163, VSIG4, and the aforementioned transcription factors and protein kinases may be involved in the biological processes that underlie cetuximab treatment of HNSCC. This study provides new perspectives to facilitate further understanding of the biological mechanism that underlies cetuximab treatment of HNSCC and the exploration of the effectiveness of HNSCC treatment.   

  1. Key words: Head and neck squamous cell carcinoma;
    Bioinformatics analysis;
    cetuximab;
    Differentially expressed genes头颈部鳞状细胞癌(head and neck squamous cell carcinoma, HNSCC)约占头颈部恶性肿瘤的95%, 多发生在口咽、下咽或口腔, 其发病率具有上升的趋势, 且预后较差［1］。如在喉癌中, 除声门型喉癌, 声门上型及声门下型患者的早期症状通常较为隐蔽, 半数以上患者就诊时即处于中晚期。尽管HNSCC的手术和综合治疗手段近年来取得了较大进展, 早期淋巴结转移和侵袭性生长等恶性病理特征仍是其术后复发及转移率高、生存率低和远期疗效差的重要因素［2］。复发性和转移性HNSCC患者的生活质量差, 通常无法进行手术治疗, 且放化疗治疗欠敏感。近年来, 肿瘤治疗的靶向类药物开始逐步应用于临床, 如上皮生长因子受体(epidermal growth factor receptor, EGFR)和血管内皮生长因子(vascular endothelial growth factor, VEGF)等。其中EGFR 特异性单克隆抗体——西妥昔单抗的问世, 为HNSCC尤其是其复发或转移性患者的有效治疗提供了可能, 但部分患者靶向药物治疗后可能出现耐药性, 从而失去继续治疗的机会［3］。HNSCC的发生、发展和疾病转归是复杂的多因素生物学过程。因此, 对西妥昔单抗靶向药物治疗中的关键基因、基因间的相互作用及调节进行探索与分析, 可能为深入理解西妥昔单抗治疗HNSCC的生物学机制、解决西妥昔单抗的耐药性问题开辟新的切入点, 从而为头颈部鳞状细胞癌的治疗提供新的思路和靶点。
  • Received:2020-04-26 Online:2020-07-20 Published:2020-08-28

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Abstract: Objective The aim of this study was to provide new perspectives and targets for the treatment of HNSCC by screening differentially expressed genes during cetuximab treatment of head and neck squamous cell carcinoma(HNSCC)using bioinformatics. Methods The chip dataset, GSE109756, was downloaded from the GEO database, and the online analysis tool, GEO2R, was used to screen differentially expressed genes in head and neck squamous cell carcinoma tissues treated with and without cetuximab. The DAVID 6.8 and STRING online software were used to analyze the function of the differentially expressed genes, their pathway enrichment, and their protein interactions. Cytoscape was used to visualize and analyze the protein interactions. The online analysis tool, X2K, was used to find the transcription factors, the kinases of differentially expressed genes, and their mutual regulatory relationship with the targeted genes. Results Ninety-one differentially expressed genes, including 50 up-regulated and 41 down-regulated genes(P<0.05; | logFC | > 1), were found in head and neck squamous cell carcinoma tissues treated with and without cetuximab. The GO and KEGG pathway analyses suggested that these differentially expressed genes were mainly enriched with immunomodulation, extracellular matrix, and other processes. Through the construction of a protein-protein interaction network, we screened CD163, VSIG4, and 3 other core differentially expressed genes(P<0.05), which were up-regulated after cetuximab treatment. In addition, our analysis shows that transcription factors, including SUZ12, TP63, and ESR1, played a key role in cetuximab treatment(P<0.05)and MAPK14, CDK1, and MAPK1 were the most important kinases during the process(P<0.05). Conclusion CD163, VSIG4, and the aforementioned transcription factors and protein kinases may be involved in the biological processes that underlie cetuximab treatment of HNSCC. This study provides new perspectives to facilitate further understanding of the biological mechanism that underlies cetuximab treatment of HNSCC and the exploration of the effectiveness of HNSCC treatment.

Key words: Head and neck squamous cell carcinoma, Bioinformatics analysis, cetuximab, Differentially expressed genes

CLC Number: 

  • R739.6
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[1] WU Jing, LIU Yehai. Targeted therapy for head and neck squamous cell carcinoma [J]. J Otolaryngol Ophthalmol Shandong Univ, 2018, 32(5): 97-102.
[2] ZHAO Jincheng, SHI Ying, ZHANG Ying, JIA Zhanhong, MA Xin, ZHANG Jingqiu, WU Zaijun, WANG Yu. Expression and methylation patterns of CDH13 in human head and neck squamous carcinoma cells. [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2017, 31(4): 60-63.
[3] YU Zi-wei, DONG Pin, PANG Zheng. Clinical study of cetuximab combined with post-operative concurrent  chemo-radiotherapy on recurrent advanced squamous cell-carcinoma of the head and neck [J]. JOURNAL OF SHANDONG UNIVERSITY (OTOLARYNGOLOGY AND OPHTHALMOLOGY), 2010, 24(6): 44-46.
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