Abstract
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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) includes cancers of the oral cavity, larynx, and oropharynx and is the sixth most common cancer worldwide [1]
Studies have revealed a similar phenomenon in patients with HNSCC, indicating that overexpressed proteins in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway may be used as good prognostic biomarkers, including p-mTOR, p-PI3K, and p-S6 [27]
Only a few studies have investigated the prognostic markers for predicting the risk of recurrence in patients with HNSCC who have undergone definitive surgery and adjuvant radiotherapy
Summary
Head and neck squamous cell carcinoma (HNSCC) includes cancers of the oral cavity, larynx, and oropharynx and is the sixth most common cancer worldwide [1]. Patients with HNSCC diagnosed in early stage (I and II) have a 60%–95% possibility of achieving successful treatment via primary tumor excision combined with extensive neck dissection, which results in a favorable outcome for long-term prognosis [6]. In two-thirds of diagnosed patients, the cancer is already in the advanced stage (III and IV) and is accompanied by tumor metastasis and recurrence, leading to poor prognosis and poor quality of life [8]. Recurrence rate in patients with HNSCC is approximately 50% within 2 years of the diagnosis of the primary tumor [9]. The use of concurrent radiotherapy or chemotherapy in the treatment of patients with HNSCC is accompanied by severe side effects, including mucositis, dysphagia, leukopenia, and thrombocytopenia, which leads to an increased risk of infection and bleeding [12]
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