Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma

Charles C.L. Tong; Mateusz Koptyra; Pichai Raman; Komal S. Rathi; Namrata Choudhari; Xiang Lin; Tyler Seckar; Zhi Wei; Michael A. Kohanski; Bert W. O'Malley; Noam A. Cohen; David W. Kennedy; Nithin D. Adappa; Erle S. Robertson; Esther Baranov; Edward C. Kuan; Peter Papagiannopoulos; Jalal B. Jalaly; Michael D. Feldman; Phillip B. Storm; Adam C. Resnick; James N. Palmer

doi:10.1002/alr.22882

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma

Charles C.L. Tong, Mateusz Koptyra, Pichai Raman, Komal S. Rathi, Namrata Choudhari, Xiang Lin, Tyler Seckar, Zhi Wei, Michael A. Kohanski, Bert W. O'Malley, Noam A. Cohen, David W. Kennedy, Nithin D. Adappa, Erle S. Robertson, Esther Baranov, Edward C. Kuan, Peter Papagiannopoulos, Jalal B. Jalaly, Michael D. Feldman, Phillip B. StormAdam C. Resnick, James N. Palmer

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

Original language	English (US)
Pages (from-to)	200-209
Number of pages	10
Journal	International Forum of Allergy and Rhinology
Volume	12
Issue number	2
DOIs	https://doi.org/10.1002/alr.22882
State	Published - Feb 2022
Externally published	Yes

All Science Journal Classification (ASJC) codes

Immunology and Allergy
Otorhinolaryngology

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10.1002/alr.22882

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Tong, C. C. L., Koptyra, M., Raman, P., Rathi, K. S., Choudhari, N., Lin, X., Seckar, T., Wei, Z., Kohanski, M. A., O'Malley, B. W., Cohen, N. A., Kennedy, D. W., Adappa, N. D., Robertson, E. S., Baranov, E., Kuan, E. C., Papagiannopoulos, P., Jalaly, J. B., Feldman, M. D., ... Palmer, J. N. (2022). Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma. International Forum of Allergy and Rhinology, 12(2), 200-209. https://doi.org/10.1002/alr.22882

@article{bbaddfe6e6d34ce68d9b4f7d80875b1b,

title = "Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma",

abstract = "Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.",

author = "Tong, {Charles C.L.} and Mateusz Koptyra and Pichai Raman and Rathi, {Komal S.} and Namrata Choudhari and Xiang Lin and Tyler Seckar and Zhi Wei and Kohanski, {Michael A.} and O'Malley, {Bert W.} and Cohen, {Noam A.} and Kennedy, {David W.} and Adappa, {Nithin D.} and Robertson, {Erle S.} and Esther Baranov and Kuan, {Edward C.} and Peter Papagiannopoulos and Jalaly, {Jalal B.} and Feldman, {Michael D.} and Storm, {Phillip B.} and Resnick, {Adam C.} and Palmer, {James N.}",

note = "Publisher Copyright: {\textcopyright} 2021 ARS-AAOA, LLC",

year = "2022",

month = feb,

doi = "10.1002/alr.22882",

language = "English (US)",

volume = "12",

pages = "200--209",

journal = "International Forum of Allergy and Rhinology",

issn = "2042-6976",

publisher = "John Wiley and Sons Inc.",

number = "2",

}

Tong, CCL, Koptyra, M, Raman, P, Rathi, KS, Choudhari, N, Lin, X, Seckar, T, Wei, Z, Kohanski, MA, O'Malley, BW, Cohen, NA, Kennedy, DW, Adappa, ND, Robertson, ES, Baranov, E, Kuan, EC, Papagiannopoulos, P, Jalaly, JB, Feldman, MD, Storm, PB, Resnick, AC & Palmer, JN 2022, 'Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma', International Forum of Allergy and Rhinology, vol. 12, no. 2, pp. 200-209. https://doi.org/10.1002/alr.22882

TY - JOUR

T1 - Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma

AU - Tong, Charles C.L.

AU - Koptyra, Mateusz

AU - Raman, Pichai

AU - Rathi, Komal S.

AU - Choudhari, Namrata

AU - Lin, Xiang

AU - Seckar, Tyler

AU - Wei, Zhi

AU - Kohanski, Michael A.

AU - O'Malley, Bert W.

AU - Cohen, Noam A.

AU - Kennedy, David W.

AU - Adappa, Nithin D.

AU - Robertson, Erle S.

AU - Baranov, Esther

AU - Kuan, Edward C.

AU - Papagiannopoulos, Peter

AU - Jalaly, Jalal B.

AU - Feldman, Michael D.

AU - Storm, Phillip B.

AU - Resnick, Adam C.

AU - Palmer, James N.

PY - 2022/2

Y1 - 2022/2

N2 - Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

AB - Background: Inverted papilloma (IP) is a sinonasal tumor with a well-known potential for malignant transformation. The purpose of this study was to identify the genes and pathways associated with IP, with progression to carcinoma-in-situ and invasive carcinoma. Methods: To determine genes and molecular pathways that may indicate progression and correlate with histologic changes, we analyzed six IP without dysplasia, five IP with carcinoma-in-situ, and 13 squamous cell carcinoma ex-IP by targeted sequencing. The HTG EdgeSeq Oncology Biomarker Panel coupled with next-generation sequencing was used to evaluate 2560 transcripts associated with solid tumors. Results: Progressive upregulation of 11 genes were observed (CALD1, COL1A1, COL3A1, COL4A2, COL5A2, FN1, ITGA5, LGALS1, MMP11, SERPINH1, SPARC) in the order of invasive carcinoma > carcinoma-in-situ > IP without dysplasia. When compared with IP without dysplasia, more genes are differentially expressed in invasive carcinoma than carcinoma-in-situ samples (341 downregulated/333 upregulated vs. 195 downregulated/156 upregulated). Gene set enrichment analysis determined three gene sets in common between the cohorts (epithelial mesenchymal transition, extracellular matrix organization, and coagulation). Conclusions: Progressive upregulation of genes specific to IP malignant degeneration has significant clinical implications. This panel of 11 genes will improve concordance of histologic classification, which can directly impact treatment and patient outcomes. Additionally, future studies on larger tumor sets may observe upregulation in the gene panel that preceded histologic changes, which may be useful for further risk stratification.

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U2 - 10.1002/alr.22882

DO - 10.1002/alr.22882

M3 - Article

C2 - 34510780

AN - SCOPUS:85114663037

SN - 2042-6976

VL - 12

SP - 200

EP - 209

JO - International Forum of Allergy and Rhinology

JF - International Forum of Allergy and Rhinology

IS - 2

ER -

Targeted gene expression profiling of inverted papilloma and squamous cell carcinoma

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