Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma are Molecularly Distinct

Alana Sorgini; Hugh Andrew Jinwook Kim; Peter Y F Zeng; Mushfiq Hassan Shaikh; Neil Mundi; Farhad Ghasemi; Eric Di Gravio; Halema Khan; Danielle MacNeil; Mohammed Imran Khan; Adrian Mendez; John Yoo; Kevin Fung; Pencilla Lang; David A Palma; Joe S Mymryk; John W Barrett; Krupal B Patel; Paul C Boutros; Anthony C Nichols

doi:10.3390/cancers13010105

Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma are Molecularly Distinct

Cancers (Basel). 2020 Dec 31;13(1):105. doi: 10.3390/cancers13010105.

Authors

Alana Sorgini¹, Hugh Andrew Jinwook Kim¹, Peter Y F Zeng¹, Mushfiq Hassan Shaikh¹, Neil Mundi¹, Farhad Ghasemi², Eric Di Gravio¹, Halema Khan¹, Danielle MacNeil^{1

3}, Mohammed Imran Khan¹, Adrian Mendez^{1

3}, John Yoo^{1

3}, Kevin Fung^{1

3}, Pencilla Lang³, David A Palma^{1

3}, Joe S Mymryk^{1

3

4}, John W Barrett^{1

3}, Krupal B Patel⁵, Paul C Boutros^{6

7

8

9

10}, Anthony C Nichols^{1

3}

Affiliations

¹ Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada.
² Department of General Surgery, University of Western Ontario, London, ON N6A 5C5, Canada.
³ Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada.
⁴ Department of Microbiology & Immunology, University of Western Ontario, London, ON N6A 5C1, Canada.
⁵ Department of Otolaryngology, Moffitt Cancer Center, Tampa, FL 33612, USA.
⁶ Department of Human Genetics, University of California, Los Angeles, CA 90095, USA.
⁷ Department of Urology, University of California, Los Angeles, CA 90095, USA.
⁸ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA.
⁹ Institute for Precision Health, University of California, Los Angeles, CA 90095, USA.
¹⁰ Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90095, USA.

Abstract

Laryngeal squamous cell carcinoma (LSCC) from different subsites have distinct presentations and prognosis. In this study, we carried out a multiomic comparison of LSCC subsites. The Cancer Genome Atlas (TCGA) LSCC cohort was analyzed in the R statistical environment for differences between supraglottic and glottic cancers in single nucleotide variations (SNVs), copy number alterations (CNAs), mRNA abundance, protein abundance, pathway overrepresentation, tumor microenvironment (TME), hypoxia status, and patient outcome. Supraglottic cancers had significantly higher overall and smoking-associated SNV mutational load. Pathway analysis revealed upregulation of muscle related pathways in glottic cancer and neural pathways in supraglottic cancer. Proteins involved in cancer relevant signaling pathways including PI3K/Akt/mTOR, the cell cycle, and PDL1 were differentially abundant between subsites. Glottic and supraglottic tumors have different molecular profiles, which may partially account for differences in presentation and response to therapy.

Keywords: HNSCC; HPV-negative; genomics; larynx cancer; mutational status.

Abstract

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