eIF4E and 4EBP1 are prognostic markers of head and neck squamous cell carcinoma recurrence after definitive surgery and adjuvant radiotherapy

Autoři: Chung-I. Huang aff001;  Chih-Chun Wang aff002;  Tzong-Shyuan Tai aff003;  Tzer-Zen Hwang aff002;  Chuan-Chien Yang aff002;  Chin-Mu Hsu aff004;  Yu-Chieh Su aff004
Působiště autorů: Department of Radiation Oncology, E-Da Cancer Hospital, Kaohsiung, Taiwan aff001;  Department of Otolaryngology, E-Da Hospital, Kaohsiung, Taiwan aff002;  Department of Medical Research, E-Da Hospital, Kaohsiung, Taiwan aff003;  Division of Hematology-Oncology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan aff004;  School of Medicine, I-Shou University, Kaohsiung, Taiwan aff005
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0225537


There is high risk of metastasis and recurrence in head and neck squamous cell carcinoma (HNSCC) patients, especially for patient who received definitive surgery and adjuvant radiotherapy. Aberrant activation of PI3K/AKT/mTOR signaling occurs in approximately 80% of HNSCC, which has been indicated to serve as prognostic biomarkers for patients suffer from recurrence or metastasis. Therefore, in this study, we focus on the relationship between the expression level of signaling factors in PI3K/AKT/mTOR pathway and recurrence tumor from HNSCC patients. A tissue microarray (TMA) was constructed from 54 cases of HNSCC patients who received definitive surgery and adjuvant radiotherapy, are followed more than 5 years, and with no previous malignancy and synchronous tumor. Slides were scored and dichotomized by two pathologists and scores. Based on the TMA block with IHC staining, the results showed that PI3K/AKT/mTOR signaling was highly activated both in recurrence and non-recurrence patients. Particularly, in the recurrence population, the results showed the low expression phospho-eukaryotic initiation factor 4E (p-eIF4E) or high expression eIF4E, phospho-eIF4E binding protein 1 (p-4EBP1), phospho-ribosomal protein S6 kinase beta-1 (p-S6K1) and phospho-40S ribosomal protein S6 (p-S6R) exhibited worse overall survival. The expression level of eIF4E and p-4EBP1 were significantly associated with tumor recurrence and recurrence-free survival. Furthermore, high expression level of eIF4E and p-4EBP1 had worse recurrence-free survival. In conclusion, the expression of eIF4E and p-4EBP1 should be considered as predictive biomarkers for the HNSCC patients. This may contribute to potential predictive biomarkers for HNSCC patient who receive adjuvant radiotherapy.

Klíčová slova:

Biomarkers – Cell staining – Head and neck squamous cell carcinoma – Metastasis – Negative staining – Radiation therapy – Staining – Surgical and invasive medical procedures


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2019 Číslo 11