Molecular Characterization of Oropharyngeal Squamous Cell Carcinoma (OPSCC) Surgical Margin

Introduction Up to 30% of OPSCC patients experience locoregional recurrence following curative surgery with adjuvant treatment. Surgical margins are assessed pathohistologically, but molecular changes predate microscopic detection of dysplasia. We aim to establish molecular signatures discriminating tumors (TU) from their respective clear resection margins (RM) & healthy mucosa (HM).

Materials/Methods Snap-frozen tissue samples of TU, RM (n=29) & HM (n=6) from OPSCC patients were obtained intraoperatively. Total RNA & DNA were extracted (Qiagen kit). DNA methylation profiling was performed using Infinium Methylation EPIC 850K, and RNASeq was performed using Illumina HiSeq2500/NovaSeq6000. Data analysis was performed in R (4.1.1).

Results Gene ontology of biological processes revealed enrichment in the modulation of extracellular matrix organization in TU. RNA of nine matrix-metalloproteinases (MMP) were expressed significantly higher in TU compared to RM-HM. Based on this MMP panel, samples clustered TU/RM with high accuracy. Contrarily, RM & HM samples clustered together. Associated DNA methylation loci reflected the significant differences between TU & RM-HM samples. Molecular oncogenesis in R0 RM demonstrated heterogeneity in the expression of markers playing a role in epithelial to mesenchymal transition (EMT). Nine cancer-testis antigens (CTA) exhibited a gradient in their expression displaying the highest expression in TU, lower expression in the RM, & almost no expression in HM.

Conclusion/Discussion We conclude that MMP, EMT key players, & CTA are candidate genes that may help to detect malignancy and premalignant conditions in surgical margins. Our goal is to establish intraoperative surgical margin assessment to guide the extent of surgical resection.

This project is currently funded by the Deutsche Forschungsgemeinschaft.

Publikationsverlauf

Artikel online veröffentlicht:
24. Mai 2022