Abstract
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-PDO(cis-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.