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[Analysis for potential targeting genes of TPF regimen induction chemotherapy in hypopharyngeal squamous cell
1Department 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.
Abstract:
Objective: 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. Methods: 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. Results: 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)(P<0.01). IL-6R was significantly downregulated in insensitive tissues (0.44±0.03) compared with sensitive tissues. (0.68±0.03) (P<0.01). Conclusion: CD44 and IL-6R may be potentially functional genes of TPF induction chemotherapy in hypopharyngeal squamous cell carcinoma.
Insights
This study identified 1,381 differentially expressed genes in hypopharyngeal cancer patients treated with TPF chemotherapy. CD44 and IL-6R were found to be key genes influencing chemotherapy sensitivity.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Hypopharyngeal squamous cell carcinoma (HPSCC) poses a significant treatment challenge.
- Induction chemotherapy with the TPF regimen (docetaxel, cisplatin, fluorouracil) is a common treatment modality.
- Understanding the molecular mechanisms of TPF chemosensitivity is crucial for improving patient outcomes.
Purpose of the Study:
- To identify differentially expressed genes associated with TPF chemotherapy sensitivity in HPSCC.
- To investigate potential functional targeting genes for HPSCC treatment.
Main Methods:
- Microarray analysis of gene expression in 29 HPSCC patients undergoing TPF chemotherapy.
- Bioinformatic analysis to identify differentially expressed genes and pathways.
- Reverse transcription and quantitative real-time PCR (RT-qPCR) to validate mRNA expression of candidate genes (CD44, IL-6R) in 43 samples.
Main Results:
- 1,381 significantly differentially expressed genes were identified between chemotherapy-sensitive and non-sensitive groups.
- Gene Ontology (GO) analysis revealed alterations in extracellular matrix, chemokine receptor binding, potassium channel activity, angiogenesis, immune response, and calcium ion binding.
- KEGG pathway analysis highlighted changes in ECM-receptor interaction, peroxisome, glutathione metabolism, and PPAR signaling.
- CD44 was significantly upregulated, and IL-6R was significantly downregulated in chemotherapy-insensitive HPSCC tissues.
Conclusions:
- CD44 and IL-6R represent potential functional genes influencing TPF induction chemotherapy response in HPSCC.
- These genes may serve as biomarkers for predicting chemosensitivity or as therapeutic targets in HPSCC.
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