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Cisplatin overcomes radiotherapy resistance in OCT4-expressing head and neck squamous cell carcinoma
- Source :
- Oral Oncology. 127:105772
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
-
Abstract
- Objectives: Cisplatin is combined with radiotherapy for advanced head and neck squamous cell carcinoma (HNSCC). While providing a beneficial effect on survival, it also causes side effects and thus is an important target when considering treatment de-escalation. Currently, there are no biomarkers to predict its patientselective therapeutic utility. In this study, we examined the role of the stem cell factor OCT4 as a potential biomarker to help clinicians stratify HNSCC patients between radiotherapy and chemoradiotherapy. Materials and methods: OCT4 immunohistochemical staining of a population-validated tissue microarray (PV-TMA) (n = 166) representative of a standard HNSCC patients was carried out, and 5-year survival was analyzed. The results were validated using ex vivo drug sensitivity analysis of HNSCC tumor samples, and further crossvalidated in independent oropharyngeal (n = 118), nasopharyngeal (n = 170), and vulvar carcinoma (n = 95) clinical datasets. In vitro, genetically modified, patient-derived HNSCC cells were used. Results: OCT4 expression in HNSCC tumors was associated with radioresistance. However, combination therapy with cisplatin was found to overcome this radioresistance in OCT4-expressing HNSCC tumors. The results were validated by using several independent patient cohorts. Furthermore, CRISPRa-based OCT4 overexpression in the HNSCC cell line resulted in apoptosis resistance, and cisplatin was found to downregulate OCT4 protein expression in vitro. Ex vivo drug sensitivity analysis of HNSCC tumors confirmed the association between OCT4 expression and cisplatin sensitivity. Conclusion: This study introduces OCT4 immunohistochemistry as a simple and cost-effective diagnostic approach for clinical practice to identify HNSCC patients benefitting from radiosensitization by cisplatin using either full or reduced dosing.
- Subjects :
- OROPHARYNGEAL CANCER
EXPRESSION
Cancer Research
3122 Cancers
OCT4
HNSCC
THERAPY
Tissue microarray
Cell Line, Tumor
TUMORIGENESIS
Humans
RECURRENT
Squamous Cell Carcinoma of Head and Neck
INDUCTION
Radioresistance
Head and Neck cancer
CHEMOTHERAPY
OPEN-LABEL
3126 Surgery, anesthesiology, intensive care, radiology
CETUXIMAB
313 Dentistry
Gene Expression Regulation, Neoplastic
Oncology
Drug Resistance, Neoplasm
Head and Neck Neoplasms
Carcinoma, Squamous Cell
Cisplatin
Oral Surgery
Subjects
Details
- ISSN :
- 13688375
- Volume :
- 127
- Database :
- OpenAIRE
- Journal :
- Oral Oncology
- Accession number :
- edsair.doi.dedup.....15a8dc3c6c4ceb07b436529e322dc4d6