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HPV oncogene and biomarker mRNA detection and quantification by Quantigene-MPH assay characterizes xenotransplanted HNSCC
Background HNSCC has different etiology that influences therapy susceptibility. Infection with human papillomaviruses (HPV) or exposure to toxic substances can lead to cellular transformation. HPV-positive tumors have a better prognosis. The knowledge of HPV association, expression of HPV oncogenes and related cellular biomarkers may be important.
Methods Primary HNSCC were transplanted onto SCID mice and PdX model lines were established. PdX tumors (n = 14) were embedded into paraffin, sections produced, lysed and analyzed by a multiplexed mRNA quantifying assay that combines detection of HPV genotype-specific oncogene expression with cellular biomarkers for proliferation, cancer stem cell, and tumor markers. The Luminex bead-based QuantiGene 2.0 technology platform (ThermoFisher Scientific) was used to quantify mRNA expression simultaneously.
Conclusions HPV positivity (6/14 HNSCC; 5xHPV16, 1xHPV33) and negativity (8/14 HNSCC) was detected according to E7/E6 oncogene mRNA expression. P16 was upregulated in 6/6 HPV+ and 4/8 HPV- HNSCC-PdX. P53 was strongly expressed in all PdX. Ki67 showed a trend for stronger expression in HPV+ HNSCC. A significantly different expression between HPV+ and HPV- PdX was found for tumor markers Stathmin, Sox, and TERT.
Conclusion Measurement of E6/E7 mRNA indicates true HPV association, and identifies HPV independent p16 expression, as well as malignancy according to biomarker expression. Quantigene-MPH based mRNA detection may be a research and diagnostic tool for HNSCC classification. Further PdX models will be investigated. Analysis of primary tumor material is warranted to validate the findings.
10 June 2020 (online)
© Georg Thieme Verlag KG
Stuttgart · New York