Comparative transcriptome analysis of sinonasal inverted papilloma and associated squamous cell carcinoma: Out-HOXing developmental genes.

Abstract

BACKGROUND:

Sinonasal papilloma has a tendency toward local destruction, recurrence, and malignant transformation. This study aimed to unravel mechanisms in the malignant transformation of sinonasal papillomas using RNA-seq.

METHODS:

The cohort consisted of 37 consecutive patients; tumor histology included a continuum spectrum (sinonasal papillomas/dysplastic/carcinomas-in-situ/invasive squamous cell carcinomas). These were microdissected and RNA was subjected to whole-transcriptome shotgun sequencing.

RESULTS:

RNA-seq and pathway analysis showed that the highest expressed genes/potential drivers were development- and differentiation-related genes. The protein expression of six highly upregulated genes (HOXA9, EN1, DUX4, CA9, CD1a, and CK5/6) validated the RNA-seq results. HOXA9 and CA9 were found to be expressed in most of the carcinoma samples but were largely negative in papillomas; all of the CA9-negative carcinomas were recurrent.

CONCLUSIONS:

We conclude that sinonasal carcinomas arising from papillomas are mainly defined by overexpressed developmental/homeobox genes, which provide the potential for transformation/plasticity, along with differentiation and proliferation behavior of neoplastic cells. Our results support HOXA9 and CA9 as biomarkers for carcinomas, with CA9 emerging as a predictive marker of recurrence.

• Authors: Diana Bell, Achim H Bell, Michael E Kupferman, Victor G Prieto, Randal S Weber, Ehab Y Hanna
• Journal: Head & neck (Head Neck) Vol. 41 Issue 9 Pg. 3090-3104 (09 2019) ISSN: 1097-0347 [Electronic] United States
• PMID: 31041828 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Antigens, Neoplasm
• Biomarkers, Tumor
• Homeodomain Proteins
• RNA, Neoplasm
• homeobox protein HOXA9
• CA9 protein, human
• Carbonic Anhydrase IX

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (genetics)
• Biomarkers, Tumor
• Carbonic Anhydrase IX (genetics)
• Carcinoma, Squamous Cell (genetics, pathology)
• Cluster Analysis
• Female
• Gene Expression Profiling
• Genes, Homeobox
• Homeodomain Proteins (genetics)
• Humans
• Male
• Middle Aged
• Nose Neoplasms (genetics, pathology)
• Papilloma, Inverted (genetics, pathology)
• Paranasal Sinus Neoplasms (genetics, pathology)
• RNA, Neoplasm (analysis)
• Sequence Analysis, RNA
• Transcriptome