通过非热等离子体激活介质治疗放射耐药头颈部鳞状细胞癌改变基因表达谱。

IF 2.9 3区 医学 Q1 OTORHINOLARYNGOLOGY
Sicong Zheng, Yudan Piao, Seung-Nam Jung, Chan Oh, Mi Ae Lim, QuocKhanh Nguyen, Shan Shen, Se-Hee Park, Shengzhe Cui, Shuyu Piao, Young Il Kim, Ji Won Kim, Ho-Ryun Won, Jae Won Chang, Yujuan Shan, Lihua Liu, Bon Seok Koo
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引用次数: 0

摘要

目的:头颈部鳞状细胞癌(HNSCC)的高复发率显著影响预后,尤其是放射耐药的HNSCC (RR-HNSCC)。非热等离子体(NTP)治疗可有效抑制HNSCC的进展;然而,NTP治疗RR-HNSCC的治疗机制尚不清楚。在本研究中,我们研究了NTP在RR-HNSCC信号通路中的调控作用,并鉴定了其特征基因。方法:在构建两个RR-HNSCC细胞系后,我们制备了非热等离子体激活培养基(NTPAM)处理或未处理的细胞裂解液,并进行RNA测序以确定其mRNA表达谱。基于RNA测序。结果:我们鉴定了差异表达基因,随后进行了生物信息学分析,以鉴定可能与NTPAM治疗RR-HNSCC相关的候选分子。结果:NTPAM可降低体外培养的RR-HNSCC细胞活力。RNA测序结果表明,NTPAM处理激活活性氧途径,诱导RR-HNSCC细胞系铁下垂。在1924个与放射治疗相关的基因中,8个在细胞系和癌症基因组图谱(TCGA)队列中均显示有统计学意义。只有ABCC3、DUSP16、PDGFB、RAF1和THBS1 5个基因在NTPAM数据测序和TCGA数据之间显示出一致的结果。LASSO回归分析显示,5个基因与肿瘤预后相关,风险比(HR)为2.26。在RR-HNSCC细胞中,NTPAM在6小时内影响DUSP16、PDGFB和THBS1作为激活标记,并持续12小时。此外,富集分析表明,这三个差异基因与ECM、TGF-β、PI3K-AKT和MET通路相关。结论:NTPAM通过诱导特异性ros介导的铁下垂增强了RR-HNSCC细胞系的细胞毒性。DUSP16、PDGFB和THBS1被确定为逆转NTPAM治疗引起的放射耐药的关键靶点,为NTPAM治疗RR-HNSCC的机制和临床应用提供了新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Altered gene expression profiling by non-thermal plasma-activated media treatment in radioresistant head and neck squamous cell carcinoma.

Objective: High recurrence rates in head and neck squamous cell carcinoma (HNSCC) significantly affect prognosis, especially in radioresistant HNSCC (RR-HNSCC). Nonthermal plasma (NTP) therapy can effectively suppress the progression of HNSCC; however, the therapeutic mechanism of NTP therapy for RR-HNSCC remains unclear. In this study, we investigated the regulatory role of NTP in the RR-HNSCC signaling pathway and identified its signature genes.

Methods: After constructing two RR-HNSCC cell lines, we prepared cell lysates from cells treated or not treated with non-thermal plasma-activated media (NTPAM) and performed RNA sequencing to determine their mRNA expression profiles. Based on the RNA sequencing.

Results: we identified differentially expressed genes, followed by bioinformatics analysis to identify candidate molecules potentially associated with NTPAM therapy for RR-HNSCC.

Results: NTPAM decreased RR-HNSCC cell viability in vitro. The RNA sequencing results indicated that NTPAM treatment activated the reactive oxygen species pathway and induced ferroptosis in RR-HNSCC cell lines. Among the 1924 genes correlated with radiation treatment, eight showed statistical significance in both the cell lines and The Cancer Genome Atlas (TCGA) cohort. Only five genes, ABCC3, DUSP16, PDGFB, RAF1, and THBS1, showed consistent results between the NTPAM data sequencing and TCGA data. LASSO regression analysis revealed that five genes were associated with cancer prognosis, with a hazard ratio (HR) of 2.26. In RR-HNSCC cells, NTPAM affected DUSP16, PDGFB, and THBS1 as the activated marker within 6 h and persisted for 12 h. Furthermore, enrichment analysis indicated that these three differential genes were associated with ECM, TGF-β, PI3K-AKT, and MET pathways.

Conclusion: NTPAM therapy enhances cytotoxicity in RR-HNSCC cell lines by inducing specific ROS-mediated ferroptosis. DUSP16, PDGFB, and THBS1 were identified as crucial targets for reversing radiation resistance induced by NTPAM therapy, providing insights into the mechanisms and clinical applications of NTPAM treatment in RR-HNSCC.

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来源期刊
CiteScore
4.90
自引率
6.70%
发文量
49
审稿时长
6-12 weeks
期刊介绍: Clinical and Experimental Otorhinolaryngology (Clin Exp Otorhinolaryngol, CEO) is an international peer-reviewed journal on recent developments in diagnosis and treatment of otorhinolaryngology-head and neck surgery and dedicated to the advancement of patient care in ear, nose, throat, head, and neck disorders. This journal publishes original articles relating to both clinical and basic researches, reviews, and clinical trials, encompassing the whole topics of otorhinolaryngology-head and neck surgery. CEO was first issued in 2008 and this journal is published in English four times (the last day of February, May, August, and November) per year by the Korean Society of Otorhinolaryngology-Head and Neck Surgery. The Journal aims at publishing evidence-based, scientifically written articles from different disciplines of otorhinolaryngology field. The readership contains clinical/basic research into current practice in otorhinolaryngology, audiology, speech pathology, head and neck oncology, plastic and reconstructive surgery. The readers are otolaryngologists, head and neck surgeons and oncologists, audiologists, and speech pathologists.
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