Distinctive roles of syntaxin binding protein 4 and its action target, TP63, in lung squamous cell carcinoma: a theranostic study for the precision medicine
| العنوان: | Distinctive roles of syntaxin binding protein 4 and its action target, TP63, in lung squamous cell carcinoma: a theranostic study for the precision medicine |
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| المؤلفون: | Erkhem-Ochir Bilguun, Ken Shirabe, Kyoichi Kaira, Takehiko Yokobori, Kimihiro Shimizu, Susumu Rokudai, Tetsunari Oyama, Masahiko Nishiyama, Reika Kawabata-Iwakawa |
| المصدر: | BMC Cancer BMC Cancer, Vol 20, Iss 1, Pp 1-14 (2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Lung Neoplasms, Vesicular Transport Proteins, Docetaxel, Kaplan-Meier Estimate, lcsh:RC254-282, Syntaxin binding, Disease-Free Survival, 03 medical and health sciences, 0302 clinical medicine, Surgical oncology, TP63, Lung squamous cell carcinoma, Genetics, Biomarkers, Tumor, Medicine, Humans, Precision Medicine, Aged, Cell Proliferation, Aged, 80 and over, TUBB3, Predictive marker, Cluster of differentiation, Molecular target, business.industry, Membrane Proteins, Kinase insert domain receptor, Biomarker, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Vascular Endothelial Growth Factor Receptor-2, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Carcinoma, Squamous Cell, Biomarker (medicine), Female, STXBP4, Drug therapy, Cisplatin, business, Research Article |
| الوصف: | Background Lung squamous cell carcinoma (LSCC) remains a challenging disease to treat, and further improvements in prognosis are dependent upon the identification of LSCC-specific therapeutic biomarkers and/or targets. We previously found that Syntaxin Binding Protein 4 (STXBP4) plays a crucial role in lesion growth and, therefore, clinical outcomes in LSCC patients through regulation of tumor protein p63 (TP63) ubiquitination. Methods To clarify the impact of STXBP4 and TP63 for LSCC therapeutics, we assessed relevance of these proteins to outcome of 144 LSCC patients and examined whether its action pathway is distinct from those of currently used drugs in in vitro experiments including RNA-seq analysis through comparison with the other putative exploratory targets and/or markers. Results Kaplan–Meier analysis revealed that, along with vascular endothelial growth factor receptor 2 (VEGFR2), STXBP4 expression signified a worse prognosis in LSCC patients, both in terms of overall survival (OS, p = 0.002) and disease-free survival (DFS, p = 0.041). These prognostic impacts of STXBP4 were confirmed in univariate Cox regression analysis, but not in the multivariate analysis. Whereas, TP63 (ΔNp63) closely related to OS (p = 0.013), and shown to be an independent prognostic factor for poor OS in the multivariate analysis (p = 0.0324). The action pathway of STXBP4 on suppression of TP63 (ΔNp63) was unique: Ingenuity pathway analysis using the knowledge database and our RNA-seq analysis in human LSCC cell lines indicated that 35 pathways were activated or inactivated in association with STXBP4, but the action pathway of STXBP4 was distinct from those of other current drug targets: STXBP4, TP63 and KDR (VEGFR2 gene) formed a cluster independent from other target genes of tumor protein p53 (TP53), tubulin beta 3 (TUBB3), stathmin 1 (STMN1) and cluster of differentiation 274 (CD274: programmed cell death 1 ligand 1, PD-L1). STXBP4 itself appeared not to be a potent predictive marker of individual drug response, but we found that TP63, main action target of STXBP4, might be involved in drug resistance mechanisms of LSCC. Conclusion STXBP4 and the action target, TP63, could afford a key to the development of precision medicine for LSCC patients. |
| تدمد: | 1471-2407 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d497159c1e8f04bc6bc7eaf5cb57f9aaTest https://pubmed.ncbi.nlm.nih.gov/32993587Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d497159c1e8f04bc6bc7eaf5cb57f9aa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712407 |
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