Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma.
OBJECTIVE
Despite significant improvement in locoregional control in the contemporary era of nasopharyngeal carcinoma (NPC) treatment, patients still suffer from a significant risk of distant metastasis (DM). Identifying those patients at risk of DM would aid in personalized treatment in the future. MicroRNAs (miRNAs) play many important roles in human cancers; hence, we proceeded to address the primary hypothesis that there is a miRNA expression signature capable of predicting DM for NPC patients.


RESULTS
The expression of 734 miRNAs was measured in 125 (Training) and 121 (Validation) clinically annotated NPC diagnostic biopsy samples. A 4-miRNA expression signature associated with risk of developing DM was identified by fitting a penalized Cox Proportion Hazard regression model to the Training data set (HR 8.25; p < 0.001), and subsequently validated in an independent Validation set (HR 3.2; p = 0.01). Pathway enrichment analysis indicated that the targets of miRNAs associated with DM appear to be converging on cell-cycle pathways.


CONCLUSIONS
This 4-miRNA signature adds to the prognostic value of the current "gold standard" of TNM staging. In-depth interrogation of these 4-miRNAs will provide important biological insights that could facilitate the discovery and development of novel molecularly targeted therapies to improve outcome for future NPC patients.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Jeff P
JP
Bruce
Department of Medicine, Stanford University, Stanford, CA, United States.
Angela B Y
AB
Hui
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Wei
W
Shi
Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Bayardo
B
Perez-Ordonez
Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Ilan
I
Weinreb
Division of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Wei
W
Xu
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Benjamin
B
Haibe-Kains
Department of Medicine, Stanford University, Stanford, CA, United States.
Daryl M
DM
Waggott
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.|Informatics and Biocomputing Program, Ontario Institute for Cancer Research, Toronto, ON, Canada.|Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
Paul C
PC
Boutros
Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
Brian
B
O'Sullivan
Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
John
J
Waldron
Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
Shao Hui
SH
Huang
Division of Medical Oncology, University of Toronto, Toronto, ON, Canada.
Eric X
EX
Chen
Department of Otolaryngology, University of Toronto, Toronto, ON, Canada.
Ralph
R
Gilbert
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.|Department of Radiation Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.|Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.
Fei-Fei
FF
Liu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D002277:Carcinoma; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D012372:ROC Curve; D059467:Transcriptome; D055815:Young Adult
D035683:MicroRNAs