Yang Y F, Fang J G, Zhong Q, Wang R, Feng L, Hou L Z, Ma H Z, Shi Q, Lian M, He S Z
Department of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery (Ministry of Education of China), Beijing Institute of Otolaryngology, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing 100730, China.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2020 Feb 7;55(2):125-132. doi: 10.3760/cma.j.issn.1673-0860.2020.02.008.
To analyze the differentially expressed genes related to the chemosensitivity with the TPF regimen for hypopharyngeal squamous cell carcinoma and to measure potential functional targeting genes expressions. Twenty-nine patients with primary hypopharyngeal cancer who underwent induction chemotherapy with TPF from January 2013 to December 2017 in Beijing Tongren Hospital were enrolled for microarray analysis, including 28 males and 1 female, aged from 43 to 73 years old. Among them, 16 patients were sensitive to chemotherapy while 13 patients were non-sensitive. Illumina Human HT-12 Bead Chip was applied to analyze the gene expressions and online bioinformatics analysis was used to analyze the differentially expressed genes. Reverse transcription and quantitative real-time PCR (RT-qPCR) was used to measure the mRNA expression of potential functional genes of TPF induction chemotherapy in 43 samples, 29 from original patients and 14 from additional patients. Graphpad prism 7.0 software was used for statistical analysis. A total of 1 381 significantly differentially expressed genes were screened out. By GO analysis, up-regulated genes included sequestering in extracellular matrix, chemokine receptor binding and potassium channel regulator activity; down-regulated genes included regulation of angiogenesis, calcium ion binding and natural killer cell activation involved in immune response. With KEGG database analysis, down-regulated pathways included ECM-receptor interaction and peroxisome and up-regulated pathways included Glutathione metabolism and PPAR signaling pathway. The expressions of CD44 and IL-6R were significantly different and appeared biologically significant. CD44 was significantly upregulated in insensitive tissues (0.54±0.06) compared with sensitive tissues (0.33±0.04)(0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (0.01). CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.
分析与下咽鳞状细胞癌TPF方案化疗敏感性相关的差异表达基因，并检测潜在功能靶向基因的表达。纳入2013年1月至2017年12月在北京同仁医院接受TPF诱导化疗的29例原发性下咽癌患者进行芯片分析，其中男性28例，女性1例，年龄43至73岁。其中，16例患者对化疗敏感，13例患者不敏感。应用Illumina Human HT-12 Bead芯片分析基因表达，并采用在线生物信息学分析差异表达基因。采用逆转录和定量实时PCR（RT-qPCR）检测43个样本中TPF诱导化疗潜在功能基因的mRNA表达，其中29个来自原患者，14个来自新增患者。使用Graphpad prism 7.0软件进行统计分析。共筛选出1381个显著差异表达基因。通过GO分析，上调基因包括细胞外基质隔离、趋化因子受体结合和钾通道调节活性；下调基因包括血管生成调节、钙离子结合和免疫反应中自然杀伤细胞激活。通过KEGG数据库分析，下调通路包括ECM-受体相互作用和过氧化物酶体，上调通路包括谷胱甘肽代谢和PPAR信号通路。CD44和IL-6R的表达差异显著且具有生物学意义。与敏感组织（0.33±0.04）相比，CD44在不敏感组织中显著上调（0.54±0.）（P<0.01）。与敏感组织（0.68±0.03）相比，IL-6R在不敏感组织中显著下调（0.44±0.03）（P<0.01）。CD44和IL-6R可能是下咽鳞状细胞癌TPF诱导化疗的潜在功能基因。
