A proteomic signature for human papillomavirus-associated oropharyngeal squamous cell carcinoma predicts patients at high risk of recurrence
- Author(s)
- Jackson, CC; Liu, JJ; Liu, HY; Williams, SG; Anees, A; Noor, Z; Lucas, N; Xavier, D; Hains, PG; Bucio-Noble, D; Aref, AT; Porceddu, SV; Ladwa, R; Whitfield, J; Reddel, RR; Zhong, Q; Panizza, BJ; Robinson, PJ;
- Journal Title
- Cancer Research Communications
- Publication Type
- Online publication before print
- Abstract
- Although HPV-positive OPSCC is associated with better prognosis than HPV-negative disease, ~30% of cases relapse despite curative-intent radiotherapy (+/- chemotherapy). We aimed to develop a proteomic signature associated with risk of recurrence within HPV+OPSCC. We analysed tumor specimens from 124 patients with T1-4N0-3M0 HPV+OPSCC: 50 patients with residual or recurrent disease within 5 years of treatment and 74 age and performance-status matched patients with no recurrence. Proteomic analysis was performed on archival FFPE primary tumor core biopsy specimens and matched normal adjacent tissues (NAT) using quantitative data-independent acquisition mass spectrometry (DIA-MS). Recurrence-free survival (RFS), both locoregional and distant, was the primary endpoint. Univariate Cox regression analysis identified peptides associated with RFS, from which a risk score was established to generate a peptide-based signature. A total of 7,597 protein groups were identified across the cohort of which 1,565 were differentially abundant between tumor and NAT, with 1,218 being significantly increased in tumors. Improved 5-year RFS (q-value <0.5) was associated with 405 differentially abundant peptides (from 233 unique proteins) within the 124 tumors. Among them a 26-peptide signature encompassing 26 protein groups was associated with RFS and was able to stratify patients into low, intermediate, or high risk of recurrence (concordance index=0.941, p < 0.0001). Data available via ProteomeXchange PXD036891. Overall, a 26-peptide signature can be used to risk stratify HPV+OPSCC. Validation of this proteomic prognostic signature in an independent cohort is required to assess its potential use in future clinical trials to better tailor initial therapy.
- Department(s)
- Radiation Oncology
- Publisher's Version
- https://doi.org/10.1158/2767-9764.Crc-23-0460
- Open Access at Publisher's Site
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Creation Date: 2025-04-08 06:06:09
Last Modified: 2025-04-08 06:21:00