Abstract P72: From Papilloma to Carcinoma: Unravelling the Transcriptomic Reprogramming in Malignant Transformation of Sinonasal Inverted Papilloma
Shen Kai Ng, Shahana R, Jaslyn Lee, Jing Liu, Joseph W Foley, Wei Keat Teo, Serene Siow, Xinni Xu, De Yun Wang, Mark Thong, Ming Liang Oon, Joshua K TayAbstract
BACKGROUND & OBJECTIVES:
Inverted papilloma (IP) is a benign yet locally aggressive sinonasal lesion, characterized by frequent disease recurrence and potential for malignant transformation, most commonly into squamous cell carcinoma (SCC). While clinical management of IPs is primarily achieved by endoscopic surgery, the underlying molecular mechanisms that drive the behavior of IPs remain poorly understood. We therefore performed RNA sequencing on a cohort of IP and IP-SCC to gain insight into their gene expression profiles.
MATERIALS AND METHODS:
FFPE tissue sections were retrieved from a retrospective cohort of patients diagnosed with IP (n=19) and IP-transformed SCC (n=3). Laser-capture microdissection (LCM) was performed to isolate epithelium of different stages, as annotated by board-certified pathologists. Sequencing was performed using specialized in-house FFPE RNA-Seq platform, with downstream bioinformatic analyses conducted using R.
RESULTS:
Our analysis of 42 gene expression libraries revealed changes in global transcriptome profile across the different disease stages (normal > hyperplasia > IP > IP-SCC). Transformation from normal epithelium to IP revealed loss of ciliary characteristics, with enrichment of processes involved in epithelium differentiation and keratinization (NES=3.30, p-adj=9.76x10-21), while dis-enriched in processes governing synthesis and function of cilium components (NES=-3.12, p-adj=1.89x10-49). In silico immune deconvolution revealed a pro-inflammatory shift, characterized by significant loss of trans-epithelial mast cells and a concomitant increase neutrophil infiltration. From IP to IP-SCCs, we identified 758 upregulated and 893 downregulated differential expressed genes (DEGs), with enrichment of pro-tumorigenic MYC (NES=3.07, p-adj=1.89x10-28) and E2F (NES=2.81, p-adj=5.97x10-20) signaling pathways.
CONCLUSION:
Our study provided comprehensive characterization of biological processes involved in IP-SCC pathogenesis and identified genes that may be associated with malignant transformation. We also demonstrated the potential use of FFPE RNA-Seq as a clinical tool for precision medicine that can accurately identify patients at risk of malignancy.
Citation Format:
Shen Kai Ng, Shahana R, Jaslyn Lee, Jing Liu, Joseph W Foley, Wei Keat Teo, Serene Siow, Xinni Xu, De Yun Wang, Mark Thong, Ming Liang Oon, Joshua K Tay. From Papilloma to Carcinoma: Unravelling the Transcriptomic Reprogramming in Malignant Transformation of Sinonasal Inverted Papilloma [abstract]. In: Proceedings of Frontiers in Cancer Science 2025; 2025 Nov 5-7; Singapore. Philadelphia (PA): AACR; Cancer Res 2026;86(13_Suppl):Abstract nr P72.