Tumor-Educated Platelet miR-18a-3p as a Novel Liquid-Biopsy Biomarker for Early Diagnosis and Chemotherapy Efficacy Monitoring in Nasopharyngeal Carcinoma.

Kaiyu Sun,Xiuqi Wei,Junli Fan,Xianqun Xu,Hui Wang,Jingyu Su,Kaidong Zhu

doi:10.3389/fonc.2021.736412

Kaiyu Sun, Xiuqi Wei + Show 5 more

Open Access

https://doi.org/10.3389/fonc.2021.736412

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Abstract

AimsTo evaluate the value of tumor-educated platelet (TEP) miR-18a-3p in the early diagnosis and chemotherapy efficacy monitoring of nasopharyngeal carcinoma (NPC).MethodsExpression levels of miR-18a-3p in platelets and plasma were detected by relative quantitative real-time PCR in NPC patients (n=54) and normal subjects (n=36). Diagnostic values of TEP miR-18a-3p for NPC was assessed by receiver operating characteristic (ROC) curve analysis. Follow up study was carried out to observe the dynamic changes of TEP miR-18a-3p with chemotherapy on 3 NPC patients.ResultsThe expression levels of TEP miR-18a-3p in NPC patients were significantly higher than that in healthy controls (p < 0.0001). ROC curve analysis showed that the area under the curve (AUC) value was 0.841, the sensitivity and specificity for the diagnosis of NPC were 87% and 72.7%. No correlation was found between expression levels of TEP miR-18a-3p and patients’ clinical parameters and their NPC tumor-node-metastasis (TNM) stage. The positive rate of TEP miR-18a-3p and EBV DNA for NPC diagnosis were 85.4% and 66.7%. TEP miR-18a-3p expression were down-regulated after 77.8% (7 of 9) of chemotherapy, and in 66.7% (2 of 3) patients, TEP miR-18a-3p levels decreased after 3 cycles of chemotherapy.ConclusionThe expression levels of TEP miR-18a-3p are upregulated in NPC and have a high probability to downregulated after chemotherapy, indicating a significant clinical value. TEP miR-18a-3p might serve as a novel type of liquid-biopsy biomarker for early diagnosis and chemotherapy efficacy monitoring in NPC.

Highlights

Nasopharyngeal carcinoma (NPC) is a common malignancy arising in the nasopharynx epithelium with a remarkable ethnic and geographic distribution
The results showed that 87% (47 of 54) of the patients had high miR-18a-3p expression, but there was no significant difference in age (p=0.392, Table 2), gender (p=0.226, Table 2), hypertension (p=0.576, Table 2), diabetes (p>0.999, Table 2), Nasopharyngitis (p=0.322, Table 2), smoking (p>0.999, Table 2), alcohol drinking (p>0.999, Table 2), degree of differentiation (p=0.436, Table 2), TNM stage (p=0.806, 0.416, 0.58, respectively, Table 2) and EBVDNA copies (p=0.392, Table 2)
Tumor-educated platelet (TEP) miR-18a-3p expression were down-regulated after 77.8% (7 of 9) of chemotherapy, in 66.7% (2 of 3) of patients, TEP miR-18a-3p levels decreased after 3 cycles of chemotherapy. (Figure 4)

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a common malignancy arising in the nasopharynx epithelium with a remarkable ethnic and geographic distribution. Symptoms of NPC include headache, neuro facial pain, neck mass, nosebleed or stuffy nose, NPC may be misdiagnosed since the early symptoms are non-specific [5]. Radiotherapy and chemotherapy remains the mainstay of primary treatment for NPC. Nonkeratinized, poorly differentiated and undifferentiated histological subtypes are sensitive to chemotherapy, while radiotherapy can cure more than 90% of patients in stage I, but patients in advanced stages have a low 5-year survival rate due to local recurrence and distant metastasis [6]. Early diagnosis of NPC is very important and necessary. Nasal endoscopic biopsy is the most commonly used method for diagnosis of NPC, but it is difficult to obtain tissue samples in early stage of the disease. There is an urgent need for the exploration of new biomarkers for non-invasive early detection

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Conclusion