Analysis for potential targeting genes of TPF regimen induction chemotherapy in hypopharyngeal squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

ABSTRACT

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.