PMID- 33396315 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210115 IS - 2072-6694 (Print) IS - 2072-6694 (Electronic) IS - 2072-6694 (Linking) VI - 13 IP - 1 DP - 2020 Dec 31 TI - Analysis of the TCGA Dataset Reveals that Subsites of Laryngeal Squamous Cell Carcinoma are Molecularly Distinct. LID - 10.3390/cancers13010105 [doi] LID - 105 AB - 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. FAU - Sorgini, Alana AU - Sorgini A AUID- ORCID: 0000-0002-4796-5286 AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Kim, Hugh Andrew Jinwook AU - Kim HAJ AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Zeng, Peter Y F AU - Zeng PYF AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Shaikh, Mushfiq Hassan AU - Shaikh MH AUID- ORCID: 0000-0001-9953-3939 AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Mundi, Neil AU - Mundi N AUID- ORCID: 0000-0001-9328-8266 AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Ghasemi, Farhad AU - Ghasemi F AD - Department of General Surgery, University of Western Ontario, London, ON N6A 5C5, Canada. FAU - Di Gravio, Eric AU - Di Gravio E AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Khan, Halema AU - Khan H AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - MacNeil, Danielle AU - MacNeil D AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Khan, Mohammed Imran AU - Khan MI AUID- ORCID: 0000-0003-3020-1324 AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Mendez, Adrian AU - Mendez A AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Yoo, John AU - Yoo J AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Fung, Kevin AU - Fung K AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Lang, Pencilla AU - Lang P AUID- ORCID: 0000-0003-3156-4450 AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Palma, David A AU - Palma DA AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Mymryk, Joe S AU - Mymryk JS AUID- ORCID: 0000-0002-3521-8005 AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Microbiology & Immunology, University of Western Ontario, London, ON N6A 5C1, Canada. FAU - Barrett, John W AU - Barrett JW AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. FAU - Patel, Krupal B AU - Patel KB AUID- ORCID: 0000-0002-2285-0386 AD - Department of Otolaryngology, Moffitt Cancer Center, Tampa, FL 33612, USA. FAU - Boutros, Paul C AU - Boutros PC AUID- ORCID: 0000-0003-0553-7520 AD - Department of Human Genetics, University of California, Los Angeles, CA 90095, USA. AD - Department of Urology, University of California, Los Angeles, CA 90095, USA. AD - Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, CA 90095, USA. AD - Institute for Precision Health, University of California, Los Angeles, CA 90095, USA. AD - Jonsson Comprehensive Cancer Centre, University of California, Los Angeles, CA 90095, USA. FAU - Nichols, Anthony C AU - Nichols AC AUID- ORCID: 0000-0002-0760-980X AD - Department of Otolaryngology, Head and Neck Surgery, University of Western Ontario, London, ON N6A 5W9, Canada. AD - Department of Oncology, University of Western Ontario, London, ON N6A 5W9, Canada. LA - eng GR - P50 CA211015/CA/NCI NIH HHS/United States GR - MOP 340674/CAPMC/CIHR/Canada GR - P30CA016042/Division of Cancer Epidemiology and Genetics, National Cancer Institute/ GR - Biology of Head and Neck Cancers Fund/Wolfe Surgical Research Professorship/ PT - Journal Article DEP - 20201231 PL - Switzerland TA - Cancers (Basel) JT - Cancers JID - 101526829 PMC - PMC7794818 OTO - NOTNLM OT - HNSCC OT - HPV-negative OT - genomics OT - larynx cancer OT - mutational status COIS- The authors declare no conflict of interest. EDAT- 2021/01/06 06:00 MHDA- 2021/01/06 06:01 PMCR- 2020/12/31 CRDT- 2021/01/05 01:12 PHST- 2020/11/25 00:00 [received] PHST- 2020/12/16 00:00 [revised] PHST- 2020/12/26 00:00 [accepted] PHST- 2021/01/05 01:12 [entrez] PHST- 2021/01/06 06:00 [pubmed] PHST- 2021/01/06 06:01 [medline] PHST- 2020/12/31 00:00 [pmc-release] AID - cancers13010105 [pii] AID - cancers-13-00105 [pii] AID - 10.3390/cancers13010105 [doi] PST - epublish SO - Cancers (Basel). 2020 Dec 31;13(1):105. doi: 10.3390/cancers13010105.