Salivary Exosomal miRNA-1307-5p Predicts Disease Aggressiveness and Poor Prognosis in Oral Squamous Cell Carcinoma Patients

被引:32
作者
Patel, Aditi [1 ]
Patel, Shanaya [1 ]
Patel, Parina [1 ]
Mandlik, Dushyant [2 ]
Patel, Kaustubh [2 ]
Tanavde, Vivek [1 ,3 ]
机构
[1] Ahmedabad Univ, Sch Arts & Sci, Biol & Life Sci, Ahmadabad 380009, Gujarat, India
[2] HCG Canc Ctr, Dept Head & Neck Oncol, Ahmadabad 380060, Gujarat, India
[3] ASTAR, Bioinformat Inst, Singapore 138671, Singapore
关键词
oral cancer; exosomes; saliva; microRNAs; prognosis; chemoresistance; CANCER;
D O I
10.3390/ijms231810639
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Salivary exosomal miRNAs as biomarkers facilitate repeated sampling, real-time disease monitoring and assessment of therapeutic response. This study identifies a single salivary exosomal miRNA prognosticator that will aid in improved patient outcome using a liquid biopsy approach. Method: Small RNA and transcriptome sequencing profiles of tumour tissues (n = 12) and salivary exosomes (n = 8) from oral cancer patients were compared to their non-cancerous counterparts. We validated these results using The Cancer Genome Atlas database and performing Real-time PCR on a large patient cohort (n = 19 tissue samples; n = 12 salivary exosomes). Potential target genes and the miRNA-mRNA networks and enriched biological pathways regulated by this microRNA were identified using computational tools. Results: Salivary exosomes (size: 30-50 nm) demonstrated a strong expression of CD47 and detectable expression of tetraspanins CD63, CD81 and CD9 by flow cytometry. miR-1307-5p was exclusively overexpressed in tissues and salivary exosomes of oral cancer patients compared to their non-cancerous counterparts. Enhanced expression of miR-1307-5p clinically correlated with poor patient survival, disease progression, aggressiveness and chemo-resistance. Transcriptome analysis suggested that miRNA-1307-5p could promote oral cancer progression by suppressing THOP1, EHF, RNF4, GET4 and RNF114. Conclusions: Salivary exosomal miRNA-1307-5p is a potential prognosticator for predicting poor survival and poor patient outcome in oral cancers.
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页数:18
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