Comparing serum protein levels can aid in differentiating HPV-negative and -positive oropharyngeal squamous cell carcinoma patients.
Aged
Aged, 80 and over
Antigens, Neoplasm
/ blood
Apolipoproteins
/ blood
Biomarkers
/ blood
Biomarkers, Tumor
/ blood
Complement C7
/ analysis
Cyclin-Dependent Kinase Inhibitor p16
/ blood
Female
Humans
Male
Middle Aged
Oropharyngeal Neoplasms
/ blood
Papillomaviridae
/ isolation & purification
Papillomavirus Infections
/ complications
Squamous Cell Carcinoma of Head and Neck
/ blood
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
02
2020
accepted:
16
05
2020
entrez:
17
6
2020
pubmed:
17
6
2020
medline:
25
8
2020
Statut:
epublish
Résumé
The surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). With a specificity of 83%, this will misclassify some patients compared with direct HPV testing. Patients who are p16INK4a-positive but HPV DNA-negative, or RNA-negative, may be unsuitable for treatment de-escalation aimed at reducing treatment-related side effects. We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone. Serum proteins from pre-treatment samples of 36 patients with OPSCC were identified and quantified using label-free mass spectrometry-based proteomics. HPV-status was determined using p16INK4a/HPV DNA and E6/E7 mRNA. Serum protein expressions were compared between groups of patients according to HPV status, using the unpaired t-test with a Benjamini-Hochberg correction. ROC curves (AUC) were calculated with SPSS (v25). Of 174 serum proteins identified, complement component C7 (C7), apolipoprotein F (ApoF) and galectin-3-Binding Protein (LGALS3BP) significantly differed between HPV-positive and -negative tumors (AUC ranging from 0.84-0.87). ApoF levels were more than twice as high in the E6/E7 mRNA HPV-positive group than HPV-negative. Serum C7, ApoF and LGALS3BP levels discriminate between HPV-positive and HPV-negative OPSCC. Further studies are needed to validate these host immunity-related proteins as markers for HPV-associated OPSCC.
Sections du résumé
BACKGROUND
The surrogate immunohistochemical marker, p16INK4a, is used in clinical practice to determine the high-risk human papillomavirus (HPV) status of oropharyngeal squamous cell carcinomas (OPSCC). With a specificity of 83%, this will misclassify some patients compared with direct HPV testing. Patients who are p16INK4a-positive but HPV DNA-negative, or RNA-negative, may be unsuitable for treatment de-escalation aimed at reducing treatment-related side effects. We aimed to identify cost-effective serum markers to improve decision making for patients at risk of misclassification by p16INK4a alone.
METHODS
Serum proteins from pre-treatment samples of 36 patients with OPSCC were identified and quantified using label-free mass spectrometry-based proteomics. HPV-status was determined using p16INK4a/HPV DNA and E6/E7 mRNA. Serum protein expressions were compared between groups of patients according to HPV status, using the unpaired t-test with a Benjamini-Hochberg correction. ROC curves (AUC) were calculated with SPSS (v25).
RESULTS
Of 174 serum proteins identified, complement component C7 (C7), apolipoprotein F (ApoF) and galectin-3-Binding Protein (LGALS3BP) significantly differed between HPV-positive and -negative tumors (AUC ranging from 0.84-0.87). ApoF levels were more than twice as high in the E6/E7 mRNA HPV-positive group than HPV-negative.
CONCLUSIONS
Serum C7, ApoF and LGALS3BP levels discriminate between HPV-positive and HPV-negative OPSCC. Further studies are needed to validate these host immunity-related proteins as markers for HPV-associated OPSCC.
Identifiants
pubmed: 32542012
doi: 10.1371/journal.pone.0233974
pii: PONE-D-20-05054
pmc: PMC7295232
doi:
Substances chimiques
Antigens, Neoplasm
0
Apolipoproteins
0
Biomarkers
0
Biomarkers, Tumor
0
Complement C7
0
Cyclin-Dependent Kinase Inhibitor p16
0
LGALS3BP protein, human
0
apolipoprotein F
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0233974Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Biochem Soc Trans. 2007 Dec;35(Pt 6):1456-60
pubmed: 18031245
Oral Oncol. 2018 Aug;83:32-37
pubmed: 30098776
Nucleic Acids Res. 2016 Dec 15;44(22):11033
pubmed: 27683222
N Engl J Med. 2010 Jul 1;363(1):24-35
pubmed: 20530316
Int J Cancer. 1996 Sep 27;68(1):34-8
pubmed: 8895537
Head Neck Pathol. 2017 Mar;11(1):41-47
pubmed: 28247229
Int J Cancer. 2002 Jul 20;100(3):318-26
pubmed: 12115547
Biomed Res Int. 2015;2015:306964
pubmed: 26448934
Mol Cell Proteomics. 2006 Jan;5(1):144-56
pubmed: 16219938
Clin Exp Immunol. 2000 Jul;121(1):8-10
pubmed: 10886232
Clin Transl Radiat Oncol. 2017 Nov 04;8:4-11
pubmed: 29594236
Papillomavirus Res. 2017 Dec;4:1-11
pubmed: 29179862
Nucleic Acids Res. 1988 Feb 11;16(3):1215
pubmed: 3344216
Eur J Cancer. 2009 Nov;45(17):2935-9
pubmed: 19766476
Br J Cancer. 2018 Jul;119(2):200-212
pubmed: 29961760
J Natl Cancer Inst. 2016 Jan 28;108(6):djv403
pubmed: 26823521
Head Neck. 2016 Dec;38(12):1780-1787
pubmed: 27248701
Eur J Cancer. 2017 Jan;70:75-82
pubmed: 27888679
Otolaryngol Head Neck Surg. 2015 Nov;153(5):758-69
pubmed: 26124261
Ann Oncol. 2018 May 1;29(5):1273-1279
pubmed: 29438466
Nat Rev Cancer. 2011 Jan;11(1):9-22
pubmed: 21160525
J Clin Oncol. 2011 Nov 10;29(32):4294-301
pubmed: 21969503
Tumour Biol. 2015 Sep;36(10):7755-64
pubmed: 25941114
Curr Opin Otolaryngol Head Neck Surg. 2017 Apr;25(2):108-112
pubmed: 28141601
Cancer Res. 2002 May 1;62(9):2535-9
pubmed: 11980646
Acta Oncol. 2018 Apr;57(4):541-551
pubmed: 29145765
Head Neck. 2019 Feb;41(2):349-357
pubmed: 30549170
Am J Otolaryngol. 2014 Jul-Aug;35(4):463-8
pubmed: 24780201
Oral Oncol. 2018 Mar;78:137-144
pubmed: 29496041
Mol Cell Proteomics. 2017 Jan;16(1):57-72
pubmed: 27895139
Blood. 2009 Apr 9;113(15):3640-8
pubmed: 19179470
Hum Pathol. 2019 Aug;90:97-105
pubmed: 31121191
Oral Oncol. 2019 Mar;90:54-66
pubmed: 30846177
Acta Otolaryngol. 2018 May;138(5):513-518
pubmed: 29161981
J Lipid Res. 2010 Dec;51(12):3524-32
pubmed: 20855565
Br J Cancer. 2013 Apr 2;108(6):1332-9
pubmed: 23412100
J Biol Chem. 1999 Jan 15;274(3):1814-20
pubmed: 9880564
J Clin Oncol. 2018 Nov 1;36(31):3152-3161
pubmed: 30188786
Dev Comp Immunol. 2017 Feb;67:464-470
pubmed: 27640368
Nat Methods. 2014 Feb;11(2):167-70
pubmed: 24336358
Int J Cancer. 2017 Mar 1;140(5):1186-1198
pubmed: 27859245
Mol Cell Biol. 1995 Jun;15(6):3256-65
pubmed: 7760821
PLoS One. 2017 Feb 24;12(2):e0172987
pubmed: 28235076
Sci Rep. 2017 Dec 1;7(1):16715
pubmed: 29196639
Oncotarget. 2016 Dec 27;7(52):86536-86546
pubmed: 27852032
J Leukoc Biol. 2018 Oct;104(4):777-786
pubmed: 29882603
Radiother Oncol. 2018 Apr;127(1):27-35
pubmed: 29295747
Ann Oncol. 2019 Apr 1;30(4):629-636
pubmed: 30657857
Int J Oncol. 2016 Jul;49(1):265-75
pubmed: 27176937
Lancet Oncol. 2014 Nov;15(12):1319-31
pubmed: 25439690