Data from Cleaved NOTCH1 Expression Pattern in Head and Neck Squamous Cell Carcinoma Is Associated with NOTCH1 Mutation, HPV Status, and High-Risk Features Article Swipe
Eleni M. Rettig
,
Christine H. Chung
,
Justin Bishop
,
Jason D. Howard
,
Rajni Sharma
,
Ryan J. Li
,
Christopher Douville
,
Rachel Karchin
,
Evgeny Izumchenko
,
David Sidransky
,
Wayne M. Koch
,
Joseph A. Califano
,
Nishant Agrawal
,
Carole Fakhry
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1940-6207.c.6544991
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.1158/1940-6207.c.6544991
The Notch pathway is frequently altered in head and neck squamous cell carcinomas (HNSCC); however, the clinical significance of NOTCH1 dysregulation is poorly understood. This study was designed to characterize expression of the transcriptionally active NOTCH1 intracellular domain (NICD1) in HNSCCs and evaluate its association with NOTCH1 mutation status and clinical parameters. IHC for NICD1 was performed on 79 previously sequenced archival HNSCCs with known NOTCH1 mutation status. Three distinct immunohistochemical staining patterns were identified: positive/peripheral (47%), positive/nonperipheral (34%), and negative (19%). NICD1 expression was associated with NOTCH1 mutation status (P < 0.001). Most NOTCH1–wild-type tumors were peripheral (55%), whereas mutated NOTCH1 tumors were most commonly negative (47%). Nonperipheral tumors were more likely than peripheral tumors to have extracapsular spread [adjusted odds ratio (aOR), 16.01; 95% confidence interval (CI), 1.92–133.46; P = 0.010] and poor differentiation (aOR, 5.27; 95% CI, 0.90–30.86; P = 0.066). Negative staining tumors tended to be poorly differentiated (aOR, 24.71; 95% CI, 1.53–399.33; P = 0.024) and were less likely to be human papillomavirus (HPV) positive (aOR, 0.043; 95% CI, 0.001–1.59; P = 0.087). NOTCH1 mutagenesis was significantly associated with HPV status, with NOTCH1–wild-type tumors more likely to be HPV positive than NOTCH1-mutated tumors (aOR, 19.06; 95% CI, 1.31–276.15; P = 0.031). TP53 disruptive mutations were not associated with NICD1 expression or NOTCH1 mutation. In conclusion, NICD1 is expressed in three distinct patterns in HNSCC that are significantly associated with high-risk features. These findings further support a dual role for NOTCH1 as both tumor suppressor and oncogene in HNSCC. Further research is necessary to clarify the role of NOTCH1 in HNSCC and understand the clinical and therapeutic implications therein. Cancer Prev Res; 8(4); 287–95. ©2015 AACR.
Related Topics
Concepts
Head and neck squamous-cell carcinoma
Mutation
Head and neck
Basal cell
Head and neck cancer
Cancer research
Medicine
Oncology
Internal medicine
Biology
Genetics
Cancer
Gene
Surgery
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1158/1940-6207.c.6544991
- OA Status
- gold
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4392685616
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4392685616Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1158/1940-6207.c.6544991Digital Object Identifier
- Title
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Data from Cleaved NOTCH1 Expression Pattern in Head and Neck Squamous Cell Carcinoma Is Associated with NOTCH1 Mutation, HPV Status, and High-Risk FeaturesWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-04-03Full publication date if available
- Authors
-
Eleni M. Rettig, Christine H. Chung, Justin Bishop, Jason D. Howard, Rajni Sharma, Ryan J. Li, Christopher Douville, Rachel Karchin, Evgeny Izumchenko, David Sidransky, Wayne M. Koch, Joseph A. Califano, Nishant Agrawal, Carole FakhryList of authors in order
- Landing page
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https://doi.org/10.1158/1940-6207.c.6544991Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://doi.org/10.1158/1940-6207.c.6544991Direct OA link when available
- Concepts
-
Head and neck squamous-cell carcinoma, Mutation, Head and neck, Basal cell, Head and neck cancer, Cancer research, Medicine, Oncology, Internal medicine, Biology, Genetics, Cancer, Gene, SurgeryTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- Related works (count)
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10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.tended | 147 |
| abstract_inverted_index.tumors | 95, 102, 109, 115, 146, 188, 197 |
| abstract_inverted_index.©2015 | 278 |
| abstract_inverted_index.(NICD1) | 38 |
| abstract_inverted_index.0.001). | 92 |
| abstract_inverted_index.0.031). | 205 |
| abstract_inverted_index.0.066). | 143 |
| abstract_inverted_index.0.087). | 177 |
| abstract_inverted_index.Further | 253 |
| abstract_inverted_index.altered | 5 |
| abstract_inverted_index.clarify | 258 |
| abstract_inverted_index.further | 238 |
| abstract_inverted_index.mutated | 100 |
| abstract_inverted_index.pathway | 2 |
| abstract_inverted_index.status, | 185 |
| abstract_inverted_index.status. | 67 |
| abstract_inverted_index.support | 239 |
| abstract_inverted_index.whereas | 99 |
| abstract_inverted_index.(HNSCC); | 13 |
| abstract_inverted_index.Negative | 144 |
| abstract_inverted_index.archival | 61 |
| abstract_inverted_index.clinical | 16, 50, 268 |
| abstract_inverted_index.commonly | 105 |
| abstract_inverted_index.designed | 27 |
| abstract_inverted_index.distinct | 69, 225 |
| abstract_inverted_index.evaluate | 42 |
| abstract_inverted_index.findings | 237 |
| abstract_inverted_index.however, | 14 |
| abstract_inverted_index.interval | 127 |
| abstract_inverted_index.mutation | 47, 66, 88 |
| abstract_inverted_index.negative | 80, 106 |
| abstract_inverted_index.oncogene | 250 |
| abstract_inverted_index.patterns | 72, 226 |
| abstract_inverted_index.positive | 169, 194 |
| abstract_inverted_index.research | 254 |
| abstract_inverted_index.squamous | 10 |
| abstract_inverted_index.staining | 71, 145 |
| abstract_inverted_index.therein. | 272 |
| abstract_inverted_index.287–95. | 277 |
| abstract_inverted_index.[adjusted | 120 |
| abstract_inverted_index.expressed | 222 |
| abstract_inverted_index.features. | 235 |
| abstract_inverted_index.high-risk | 234 |
| abstract_inverted_index.mutation. | 217 |
| abstract_inverted_index.mutations | 208 |
| abstract_inverted_index.necessary | 256 |
| abstract_inverted_index.performed | 56 |
| abstract_inverted_index.sequenced | 60 |
| abstract_inverted_index.associated | 85, 182, 211, 232 |
| abstract_inverted_index.carcinomas | 12 |
| abstract_inverted_index.confidence | 126 |
| abstract_inverted_index.disruptive | 207 |
| abstract_inverted_index.expression | 30, 83, 214 |
| abstract_inverted_index.frequently | 4 |
| abstract_inverted_index.peripheral | 97, 114 |
| abstract_inverted_index.previously | 59 |
| abstract_inverted_index.suppressor | 248 |
| abstract_inverted_index.understand | 266 |
| abstract_inverted_index.association | 44 |
| abstract_inverted_index.conclusion, | 219 |
| abstract_inverted_index.identified: | 74 |
| abstract_inverted_index.mutagenesis | 179 |
| abstract_inverted_index.parameters. | 51 |
| abstract_inverted_index.therapeutic | 270 |
| abstract_inverted_index.understood. | 23 |
| abstract_inverted_index.characterize | 29 |
| abstract_inverted_index.implications | 271 |
| abstract_inverted_index.significance | 17 |
| abstract_inverted_index.0.001–1.59; | 174 |
| abstract_inverted_index.0.90–30.86; | 140 |
| abstract_inverted_index.Nonperipheral | 108 |
| abstract_inverted_index.dysregulation | 20 |
| abstract_inverted_index.extracapsular | 118 |
| abstract_inverted_index.intracellular | 36 |
| abstract_inverted_index.significantly | 181, 231 |
| abstract_inverted_index.1.31–276.15; | 202 |
| abstract_inverted_index.1.53–399.33; | 156 |
| abstract_inverted_index.1.92–133.46; | 129 |
| abstract_inverted_index.differentiated | 151 |
| abstract_inverted_index.papillomavirus | 167 |
| abstract_inverted_index.<i>Cancer | 273 |
| abstract_inverted_index.differentiation | 135 |
| abstract_inverted_index.transcriptionally | 33 |
| abstract_inverted_index.immunohistochemical | 70 |
| abstract_inverted_index.positive/peripheral | 75 |
| abstract_inverted_index.<i>P</i> | 130, 141, 157, 175, 203 |
| abstract_inverted_index.(<i>P</i> | 90 |
| abstract_inverted_index.positive/nonperipheral | 77 |
| abstract_inverted_index.<i>TP53</i> | 206 |
| abstract_inverted_index.<i>NOTCH1</i> | 19, 46, 65, 87, 101, 178, 216, 244, 262 |
| abstract_inverted_index.<div>Abstract<p>The | 0 |
| abstract_inverted_index.<i>NOTCH1</i>-mutated | 196 |
| abstract_inverted_index.<i>NOTCH1</i>–wild-type | 94, 187 |
| abstract_inverted_index.AACR</i>.</p></div> | 279 |
| cited_by_percentile_year | |
| countries_distinct_count | 0 |
| institutions_distinct_count | 14 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/1 |
| sustainable_development_goals[0].score | 0.7200000286102295 |
| sustainable_development_goals[0].display_name | No poverty |
| citation_normalized_percentile.value | 0.40867409 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | False |