Open Access

ARTICLE

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

by CHUAN JIANG^1,2, CHUNLEI LIU^1,3, XI YAO^1,3, JINGYA SU^1,2, WEI LU^1,3, ZHENGBO WEI^3,*, YING XIE^1,2,*

1 Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry ofEducation, 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

* Corresponding Authors: ZHENGBO WEI. Email: ; YING XIE. Email:

Oncology Research 2024, 32(12), 1935-1948. https://doi.org/10.32604/or.2024.052244

Received 27 March 2024; Accepted 06 May 2024; Issue published 13 November 2024

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.

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