Detection of Head and Neck Cancer Based on Longitudinal Changes in Serum Protein Abundance

Journal Article · 12 June 2020 · Cancer Epidemiology, Biomarkers and Prevention

DOI: https://doi.org/10.1158/1055-9965.epi-20-0192 · OSTI ID:1661886

Lee, Ju Yeon ^[1]; Shi, Tujin ^[2]; Petyuk, Vladislav A.  ^[2]; Schepmoes, Athena A.  ^[2]; Fillmore, Thomas L. ^[2]; Wang, Yi-Ting ^[2]; Cardoni, Wayne ^[3]; Coppit, George ^[3]; Srivastava, Shiv ^[4]; Goodman, Joseph F.  ^[4]; Shriver, Craig D.  ^[5]; Liu, Tao  ^[2]; Rodland, Karin D.  ^[6]

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1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Korea Basic Science Inst., Cheongju (South Korea). Research Center for Bioconvergence Analysis
2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
3. Walter Reed National Military Medical Center, Bethesda, MD (United States)
4. George Washington Univ., Washington, DC (United States)
5. Uniformed Services Univ. of the Health Sciences, Bethesda, MD (United States). John P. Murtha Cancer Center; Uniformed Services Univ. and Walter Reed National Military Medical Center, Bethesda, MD (United States)
6. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Oregon Health and Science Univ., Portland, OR (United States)

Head and Neck Squamous Cell Carcinoma (HNSCC) is significantly represented in the military population with substantial impact on military operations. Two-thirds of new HNSCC cases are first diagnosed at advanced stage III or IV with lymph node metastases. Thus, there is an urgent need of biomarkers for early detection and risk stratification. Archived serum samples from the Department of Defense Serum Repository provide a unique resource for longitudinal studies of HNSCC in the military and the identification of early detection biomarkers. Methods: We identified 175 patients diagnosed with HNSCC with 175 matched healthy controls and retrieved a total of 978 serum samples drawn at the time of diagnosis, 2 and 4 years prior to diagnosis, and 2 years after diagnosis. Following immunoaffinity depletion, serum samples were analyzed by targeted proteomics assays for multiplexed quantification of a panel of 146 candidate protein biomarkers from the curated literature. Results: We derived a 13-protein signature that distinguishes case versus controls based on longitudinal changes in serum protein concentration. The abundances of each of the 13 proteins remain constant over time in control subjects. The area under the curve for the derived random forest classifier was 0.90. Conclusions: This 13-protein classifier is highly promising for detection of HNSCC prior to overt symptoms. Impact: Use of longitudinal samples has significant potential to identify biomarkers for detection and risk stratification.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States). Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER)
• Grant/Contract Number: AC05-76RL01830
• OSTI ID: 1661886
• Report Number(s): PNNL-ACT-SA-10471
• Journal Information: Cancer Epidemiology, Biomarkers and Prevention, Vol. 29, Issue 8; ISSN 1055-9965
• Publisher: American Association for Cancer Research (AACR)Copyright Statement
• Country of Publication: United States
• Language: English