Tags

Type your tag names separated by a space and hit enter

Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma.
J Transl Med. 2020 Jul 10; 18(1):280.JT

Abstract

BACKGROUND

Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC.

METHODS

Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature.

RESULTS

A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone.

CONCLUSIONS

We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers.

Authors+Show Affiliations

Flinders Health and Medical Research Institute, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia.Flinders Health and Medical Research Institute, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia.Flinders Health and Medical Research Institute, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia.Flinders Health and Medical Research Institute, Flinders University , Bedford Park, South Australia, 5042, Australia.Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, 5000, Australia.Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, 5000, Australia.Royal Adelaide Hospital and University of Adelaide, Adelaide, South Australia, 5000, Australia.Royal Adelaide Hospital, University of Adelaide, Adelaide, South Australia, 5000, Australia. Flinders University, South Australia, South Australia, 5042, Australia.Flinders Health and Medical Research Institute, Flinders University , Bedford Park, South Australia, 5042, Australia.Department of Otorhinolaryngology Head & Neck, Monash Health and Department of Surgery, Monash University, Clayton, Victoria, 3168, Australia.Flinders Health and Medical Research Institute, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia.Flinders Health and Medical Research Institute, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia.Flinders Health and Medical Research Institute, Flinders University and Flinders Medical Centre, Bedford Park, South Australia, 5042, Australia. damian.hussey@flinders.edu.au.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32650803

Citation

Mayne, G C., et al. "Cross Validated Serum Small Extracellular Vesicle microRNAs for the Detection of Oropharyngeal Squamous Cell Carcinoma." Journal of Translational Medicine, vol. 18, no. 1, 2020, p. 280.
Mayne GC, Woods CM, Dharmawardana N, et al. Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma. J Transl Med. 2020;18(1):280.
Mayne, G. C., Woods, C. M., Dharmawardana, N., Wang, T., Krishnan, S., Hodge, J. C., Foreman, A., Boase, S., Carney, A. S., Sigston, E. A. W., Watson, D. I., Ooi, E. H., & Hussey, D. J. (2020). Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma. Journal of Translational Medicine, 18(1), 280. https://doi.org/10.1186/s12967-020-02446-1
Mayne GC, et al. Cross Validated Serum Small Extracellular Vesicle microRNAs for the Detection of Oropharyngeal Squamous Cell Carcinoma. J Transl Med. 2020 Jul 10;18(1):280. PubMed PMID: 32650803.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cross validated serum small extracellular vesicle microRNAs for the detection of oropharyngeal squamous cell carcinoma. AU - Mayne,G C, AU - Woods,C M, AU - Dharmawardana,N, AU - Wang,T, AU - Krishnan,S, AU - Hodge,J C, AU - Foreman,A, AU - Boase,S, AU - Carney,A S, AU - Sigston,E A W, AU - Watson,D I, AU - Ooi,E H, AU - Hussey,D J, Y1 - 2020/07/10/ PY - 2020/05/17/received PY - 2020/07/02/accepted PY - 2020/7/12/entrez PY - 2020/7/12/pubmed PY - 2020/7/12/medline KW - Biomarkers KW - Data analysis KW - Oropharyngeal squamous cell carcinoma KW - Serum KW - microRNAs SP - 280 EP - 280 JF - Journal of translational medicine JO - J Transl Med VL - 18 IS - 1 N2 - BACKGROUND: Oropharyngeal squamous cell carcinoma (OPSCC) is often diagnosed at an advanced stage because the disease often causes minimal symptoms other than metastasis to neck lymph nodes. Better tools are required to assist with the early detection of OPSCC. MicroRNAs (miRNAs, miRs) are potential biomarkers for early head and neck squamous cell cancer diagnosis, prognosis, recurrence, and presence of metastatic disease. However, there is no widespread agreement on a panel of miRNAs with clinically meaningful utility for head and neck squamous cell cancers. This could be due to variations in the collection, storage, pre-processing, and isolation of RNA, but several reports have indicated that the selection and reproducibility of biomarkers has been widely affected by the methods used for data analysis. The primary analysis issues appear to be model overfitting and the incorrect application of statistical techniques. The purpose of this study was to develop a robust statistical approach to identify a miRNA signature that can distinguish controls and patients with inflammatory disease from patients with human papilloma virus positive (HPV +) OPSCC. METHODS: Small extracellular vesicles were harvested from the serum of 20 control patients, 20 patients with gastroesophageal reflux disease (GORD), and 40 patients with locally advanced HPV + OPSCC. MicroRNAs were purified, and expression profiled on OpenArray™. A novel cross validation method, using lasso regression, was developed to stabilise selection of miRNAs for inclusion in a prediction model. The method, named StaVarSel (for Stable Variable Selection), was used to derive a diagnostic biomarker signature. RESULTS: A standard cross validation approach was unable to produce a biomarker signature with good cross validated predictive capacity. In contrast, StaVarSel produced a regression model containing 11 miRNA ratios with potential clinical utility. Sample permutations indicated that the estimated cross validated prediction accuracy of the 11-miR-ratio model was not due to chance alone. CONCLUSIONS: We developed a novel method, StaVarSel, that was able to identify a panel of miRNAs, present in small extracellular vesicles derived from blood serum, that robustly cross validated as a biomarker for the detection of HPV + OPSCC. This approach could be used to derive diagnostic biomarkers of other head and neck cancers. SN - 1479-5876 UR - https://www.unboundmedicine.com/medline/citation/32650803/Cross_validated_serum_small_extracellular_vesicle_microRNAs_for_the_detection_of_oropharyngeal_squamous_cell_carcinoma L2 - https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-020-02446-1 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.