Deregulation of SYCP2 predicts early stage human papillomavirus-positive oropharyngeal carcinoma: A prospective whole transcriptome analysis.
This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT-quantitative real-time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin-fixed, paraffin-embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high-risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV-associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV-associated cancer development. If further corroborated, this data may contribute to the development of a non-invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945).
Department of Pathology, University of Cambridge, Cambridge, UK.|Department of Otorhinolaryngology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Liam
L
Masterson
Department of Pathology, University of Cambridge, Cambridge, UK.
Frederic
F
Sorgeloos
Department of Pathology, University of Cambridge, Cambridge, UK.
David
D
Winder
University College London Cancer Institute, London, UK.
Matt
M
Lechner
Department of Histopathology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Alison
A
Marker
Department of Histopathology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Shalini
S
Malhotra
Department of Otolaryngology, Head and Neck Surgery, Bielefeld Academic Teaching Hospital, Bielefeld, Germany.
Holger
H
Sudhoff
Department of Otorhinolaryngology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Piyush
P
Jani
Department of Pathology, University of Cambridge, Cambridge, UK.
Peter
P
Goon
Department of Pathology, University of Cambridge, Cambridge, UK.|Department of Dermatology, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK.
Jane
J
Sterling
D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D061346:Laser Capture Microdissection; D008297:Male; D008969:Molecular Sequence Data; D009959:Oropharyngeal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000821:virology*; D030361:Papillomavirus Infections / Q000150:complications*; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D059467:Transcriptome
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C534707:SYCP2 protein, human
Diagnosis by tumor markers and biomarkers; Rb/p16-related genes; human papillomavirus; mRNA expression analysis; oropharyngeal carcinoma