posted on 2021-11-30, 16:13authored byAllen S. Ho, Aaron Robinson, Wonwoo Shon, Anna Laury, Koen Raedschelders, Vidya Venkatraman, Ronald Holewinski, Yi Zhang, Stephen L. Shiao, Michelle M. Chen, Jon Mallen-St. Clair, De-Chen Lin, Zachary S. Zumsteg, Jennifer E. Van Eyk
Deintensification therapy for human
papillomavirus-related oropharyngeal
squamous cell carcinoma (HPV(+) OPSCC) is under active investigation.
An adaptive treatment approach based on molecular stratification could
identify high-risk patients predisposed to recurrence and better select
for appropriate treatment regimens. Collectively, 40 HPV(+) OPSCC
FFPE samples (20 disease-free, 20 recurrent) were surveyed using mass
spectrometry-based proteomic analysis via data-independent acquisition
to obtain fold change and false discovery differences. Ten-year overall
survival was 100.0 and 27.7% for HPV(+) disease-free and recurrent
cohorts, respectively. Of 1414 quantified proteins, 77 demonstrated
significant differential expression. Top enriched functional pathways
included those involved in programmed cell death (73 proteins, p = 7.43 × 10–30), apoptosis (73
proteins, p = 5.56 × 10–9),
β-catenin independent WNT signaling (47 proteins, p = 1.45 × 10–15), and Rho GTPase signaling
(69 proteins, p = 1.09 × 10–5). PFN1 (p = 1.0 × 10–3),
RAD23B (p = 2.9 × 10–4), LDHB
(p = 1.0 × 10–3), and HINT1
(p = 3.8 × 10–3) pathways
were significantly downregulated in the recurrent cohort. On functional
validation via immunohistochemistry (IHC) staining, 46.9% (PFN1),
71.9% (RAD23B), 59.4% (LDHB), and 84.4% (HINT1) of cases were corroborated
with mass spectrometry findings. Development of a multilateral molecular
signature incorporating these targets may characterize high-risk disease,
predict treatment response, and augment current management paradigms
in head and neck cancer.