CES1 is associated with cisplatin resistance and poor prognosis of head and neck squamous cell carcinoma  

作　　者：CHUAN JIANG CHUNLEI LIU XI YAO JINGYA SU WEI LU ZHENGBO WEI YING XIE 

机构地区：[1]Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University),Ministry of Education,Nanning,530000,China [2]Life Sciences Institute,Guangxi Medical University,Nanning,530000,China [3]Department of Head and Neck Tumor Surgery,Affiliated Tumor Hospital of Guangxi Medical University,Nanning,530000,China

出　　处：《Oncology Research》2024年第12期1935-1948,共14页肿瘤学研究（英文）

基　　金：supported by the National Natural Science Foundation of China(No.82160386);the Guangxi Natural Science Foundation of China(No.2024GXNSFDA010032,2023GXNSFAA026189).

摘　　要：Background:Head and neck squamous cell carcinoma(HNSCC)is a prevalent form of cancer globally,with chemoresistance posing a major challenge in treatment outcomes.The efficacy of the commonly used chemotherapeutic agent,cisplatin,is diminished in patients with poor prognoses.Methods:Various bioinformatics databases were utilized to examine Carboxylesterase 1(CES1)gene expression,clinicopathologic features,patient survival analysis,and gene function.An organoid model of HNSCC was established,along with the induction of drug-resistant HNSCC in the organoid model.CES1 expression was assessed using qRT-PCR and Western Blot,and differential markers were identified through transcriptome sequencing.Knockdown and overexpression models of CES1 were created in SCC-9 and patient-derived organoid(PDO)cells using shRNA and lentivirus to investigate the tumor biology and cisplatin resistance associated with CES1.Results:Research in bioinformatics has uncovered a strong correlation between the expression level of CES1 and the prognosis of HNSCC.The data suggests a significant link between CES1 expression and tobacco smoking.RNA-sequencing revealed a notable increase in CES1 expression in HNSCC-PDOcis-R cells compared to the parental PDO cells.Subsequently,we performed in vitro studies by HNSCC-PDO and SCC-9 and found that CES1-overexpressing cells exhibited reduced sensitivity to cisplatin and stronger tumor malignant biological behavior compared with CES1-knockdown cells.Conclusion:The observed association between CES1 expression and tobacco smoking implies a potential influence of smoking on the efficacy of cisplatin-based chemotherapy in HNSCC through the regulation of CES1 expression.

关 键 词：Carboxylesterase 1(CES1) Head and neck squamous cell carcinoma(HNSCC) CHEMORESISTANCE CISPLATIN SMOKING PROGNOSIS 

分 类 号：R739.91[医药卫生—肿瘤]