EGFR as a biomarker of smoking status and survival in oropharyngeal squamous cell carcinoma

EGFR 作为口咽鳞状细胞癌吸烟状况和生存的生物标志物

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作者:Shanmugappiriya Sivarajah, Morris Kostiuk, Cameron Lindsay, Lakshmi Puttagunta, Daniel A O'Connell, Jeffrey Harris, Hadi Seikaly, Vincent L Biron

Background

This study aims to investigate EGFR as a prognostic biomarker in oropharyngeal squamous cell carcinoma (OPSCC).

Conclusions

Total EGFR tumor levels are predictive of 5-year DSS. EGFR levels correlate with. smoking and could be an objective marker for this disease etiology.

Methods

OPSCC patients from retrospective (1998-2009) and prospective cohorts (2014-2017) were included. Retrospectively collected tumors were used to construct tissue microarrays (TMAs), which were stained with EGFR, p16, DAPI and Pan-cytokeratin, and digitally quantified. EGFR, CDKN2A and HPV E6/7 levels from prospectively collected OPSCC was measured by droplet digital PCR (ddPCR). Biomarkers were compared to patient covariates, factors and survival outcomes.

Results

A total of 249 patients were included retrospectively and 64 patients were enrolled prospectively. p16 status (p < 0.001), smoking above 10 pack years (p = 0.04), smoking above 20 pack years (p < 0.001), total EGFR tumor levels (p = 0.016), and high EGFR within high or low Ki67 tumor nuclear staining (p = 0.03) were found to be significant predictors of 5-year disease specific survival (DSS). A Cox proportional hazard model of DSS showed smoking status and eGFR expression to be dependent of each other on predicting 5-year DSS. ddPCR analysis showed a significant association between smoking status and EGFR levels. Conclusions: Total EGFR tumor levels are predictive of 5-year DSS. EGFR levels correlate with. smoking and could be an objective marker for this disease etiology.

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