Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma
•NOTCH1 was frequently expressed in head and neck squamous cell carcinomas (HNSCC).•NOTCH1 expression correlated with HES1 and p21 expression.•NOTCH1/HES1/p21 positive cases had a significantly better prognosis.•Our results suggest a tumor suppressor function for NOTCH signaling in HNSCC. The functi...
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| Veröffentlicht in: | Oral oncology 2020-11, Vol.110, p.105003-105003, Article 105003 |
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| creator | Grilli, Gianluigi Hermida-Prado, Francisco Álvarez-Fernández, Mónica Allonca, Eva Álvarez-González, Miguel Astudillo, Aurora Moreno-Bueno, Gema Cano, Amparo García-Pedrero, Juana M. Rodrigo, Juan P. |
| description | •NOTCH1 was frequently expressed in head and neck squamous cell carcinomas (HNSCC).•NOTCH1 expression correlated with HES1 and p21 expression.•NOTCH1/HES1/p21 positive cases had a significantly better prognosis.•Our results suggest a tumor suppressor function for NOTCH signaling in HNSCC.
The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis.
Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients.
Membranous NOTCH1 expression was detected in 197 (61%) out of 324 evaluable tumor samples, and nuclear NOTCH1 expression in 91 samples (28%). Nuclear HES1 expression was found in 224 (67%) cases. Membranous and nuclear NOTCH1 expression were consistently and significantly correlated with nuclear HES1 (P |
| doi_str_mv | 10.1016/j.oraloncology.2020.105003 |
| format | Article |
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The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis.
Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients.
Membranous NOTCH1 expression was detected in 197 (61%) out of 324 evaluable tumor samples, and nuclear NOTCH1 expression in 91 samples (28%). Nuclear HES1 expression was found in 224 (67%) cases. Membranous and nuclear NOTCH1 expression were consistently and significantly correlated with nuclear HES1 (P < 0.001) and p21 (P = 0.03) expression, but not with Cyclin D1. NOTCH1 expression was significantly associated to early stages (I-II), non-recurrent disease, and better disease-specific (DSS) and overall survival (OS) rates (P < 0.001). Moreover, triple-positive cases (NOTCH1+/HES1+/p21+) exhibited significantly improved DSS (P < 0.001) and OS (P = 0.004), thus reinforcing the association of NOTCH pathway activation with a better prognosis in HNSCC. Multivariate analysis further revealed membranous NOTCH1 expression as a robust independent predictor of better DSS (HR = 0.554; 95% IC 0.412–0.745; P < 0.001) and better OS (HR = 0.640; 95% CI 0.491–0.835; P = 0.001).
These findings show the association of NOTCH pathway activation with a better prognosis in HNSCC patients, also revealing membranous NOTCH1 expression as a robust independent predictor of improved survival. Accordingly, these results suggest a tumor suppressive rather than an oncogenic role for NOTCH pathway in HNSCC.</description><identifier>ISSN: 1368-8375</identifier><identifier>EISSN: 1879-0593</identifier><identifier>DOI: 10.1016/j.oraloncology.2020.105003</identifier><language>eng</language><publisher>Elsevier Ltd</publisher><subject>Head and neck squamous cell carcinoma ; HES1 ; NOTCH1 ; Prognosis ; Survival</subject><ispartof>Oral oncology, 2020-11, Vol.110, p.105003-105003, Article 105003</ispartof><rights>2020 Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-c5600c938bf507281192641f81d9429be90a82eca0f1261121d7d17a549334d53</citedby><cites>FETCH-LOGICAL-c409t-c5600c938bf507281192641f81d9429be90a82eca0f1261121d7d17a549334d53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.oraloncology.2020.105003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids></links><search><creatorcontrib>Grilli, Gianluigi</creatorcontrib><creatorcontrib>Hermida-Prado, Francisco</creatorcontrib><creatorcontrib>Álvarez-Fernández, Mónica</creatorcontrib><creatorcontrib>Allonca, Eva</creatorcontrib><creatorcontrib>Álvarez-González, Miguel</creatorcontrib><creatorcontrib>Astudillo, Aurora</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><creatorcontrib>Cano, Amparo</creatorcontrib><creatorcontrib>García-Pedrero, Juana M.</creatorcontrib><creatorcontrib>Rodrigo, Juan P.</creatorcontrib><title>Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma</title><title>Oral oncology</title><description>•NOTCH1 was frequently expressed in head and neck squamous cell carcinomas (HNSCC).•NOTCH1 expression correlated with HES1 and p21 expression.•NOTCH1/HES1/p21 positive cases had a significantly better prognosis.•Our results suggest a tumor suppressor function for NOTCH signaling in HNSCC.
The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis.
Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients.
Membranous NOTCH1 expression was detected in 197 (61%) out of 324 evaluable tumor samples, and nuclear NOTCH1 expression in 91 samples (28%). Nuclear HES1 expression was found in 224 (67%) cases. Membranous and nuclear NOTCH1 expression were consistently and significantly correlated with nuclear HES1 (P < 0.001) and p21 (P = 0.03) expression, but not with Cyclin D1. NOTCH1 expression was significantly associated to early stages (I-II), non-recurrent disease, and better disease-specific (DSS) and overall survival (OS) rates (P < 0.001). Moreover, triple-positive cases (NOTCH1+/HES1+/p21+) exhibited significantly improved DSS (P < 0.001) and OS (P = 0.004), thus reinforcing the association of NOTCH pathway activation with a better prognosis in HNSCC. Multivariate analysis further revealed membranous NOTCH1 expression as a robust independent predictor of better DSS (HR = 0.554; 95% IC 0.412–0.745; P < 0.001) and better OS (HR = 0.640; 95% CI 0.491–0.835; P = 0.001).
These findings show the association of NOTCH pathway activation with a better prognosis in HNSCC patients, also revealing membranous NOTCH1 expression as a robust independent predictor of improved survival. Accordingly, these results suggest a tumor suppressive rather than an oncogenic role for NOTCH pathway in HNSCC.</description><subject>Head and neck squamous cell carcinoma</subject><subject>HES1</subject><subject>NOTCH1</subject><subject>Prognosis</subject><subject>Survival</subject><issn>1368-8375</issn><issn>1879-0593</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNqNkM1OwzAQhCMEEqXwDhYnLilrO05ibqj8SpW4wNlyHSdxSezUdkF9exKFA0dOu9LOjGa_JLnGsMKA89vdynnZOatc55rjigCZDgyAniQLXBY8Bcbp6bjTvExLWrDz5CKEHQAwzGCRyNd-kCoiVyPrompRMI2VnbENchbFVqPBu8a6YMKkGWQ02saAvk1sUatlhaStkNXqE4X9QfbuEJDSXYeU9MpY18vL5KyWXdBXv3OZfDw9vq9f0s3b8-v6fpOqDHhMFcsBFKfltmZQkBJjTvIM1yWueEb4VnOQJdFKQo1JjjHBVVHhQrKMU5pVjC6Tmzl3LLw_6BBFb8JURVo9thIkyygjuOT5KL2bpcq7ELyuxeBNL_1RYBATV7ETf7mKiauYuY7mh9msx2e-jPYiqJGJ0pXxWkVROfOfmB8wCYf-</recordid><startdate>202011</startdate><enddate>202011</enddate><creator>Grilli, Gianluigi</creator><creator>Hermida-Prado, Francisco</creator><creator>Álvarez-Fernández, Mónica</creator><creator>Allonca, Eva</creator><creator>Álvarez-González, Miguel</creator><creator>Astudillo, Aurora</creator><creator>Moreno-Bueno, Gema</creator><creator>Cano, Amparo</creator><creator>García-Pedrero, Juana M.</creator><creator>Rodrigo, Juan P.</creator><general>Elsevier Ltd</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202011</creationdate><title>Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma</title><author>Grilli, Gianluigi ; Hermida-Prado, Francisco ; Álvarez-Fernández, Mónica ; Allonca, Eva ; Álvarez-González, Miguel ; Astudillo, Aurora ; Moreno-Bueno, Gema ; Cano, Amparo ; García-Pedrero, Juana M. ; Rodrigo, Juan P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-c5600c938bf507281192641f81d9429be90a82eca0f1261121d7d17a549334d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Head and neck squamous cell carcinoma</topic><topic>HES1</topic><topic>NOTCH1</topic><topic>Prognosis</topic><topic>Survival</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Grilli, Gianluigi</creatorcontrib><creatorcontrib>Hermida-Prado, Francisco</creatorcontrib><creatorcontrib>Álvarez-Fernández, Mónica</creatorcontrib><creatorcontrib>Allonca, Eva</creatorcontrib><creatorcontrib>Álvarez-González, Miguel</creatorcontrib><creatorcontrib>Astudillo, Aurora</creatorcontrib><creatorcontrib>Moreno-Bueno, Gema</creatorcontrib><creatorcontrib>Cano, Amparo</creatorcontrib><creatorcontrib>García-Pedrero, Juana M.</creatorcontrib><creatorcontrib>Rodrigo, Juan P.</creatorcontrib><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Oral oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grilli, Gianluigi</au><au>Hermida-Prado, Francisco</au><au>Álvarez-Fernández, Mónica</au><au>Allonca, Eva</au><au>Álvarez-González, Miguel</au><au>Astudillo, Aurora</au><au>Moreno-Bueno, Gema</au><au>Cano, Amparo</au><au>García-Pedrero, Juana M.</au><au>Rodrigo, Juan P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma</atitle><jtitle>Oral oncology</jtitle><date>2020-11</date><risdate>2020</risdate><volume>110</volume><spage>105003</spage><epage>105003</epage><pages>105003-105003</pages><artnum>105003</artnum><issn>1368-8375</issn><eissn>1879-0593</eissn><abstract>•NOTCH1 was frequently expressed in head and neck squamous cell carcinomas (HNSCC).•NOTCH1 expression correlated with HES1 and p21 expression.•NOTCH1/HES1/p21 positive cases had a significantly better prognosis.•Our results suggest a tumor suppressor function for NOTCH signaling in HNSCC.
The function of NOTCH signaling (oncogenic or oncosuppressive) remains controversial in head and neck squamous cell carcinomas (HNSCC). The purpose of this work is to investigate the role of NOTCH pathway in HNSCC prognosis.
Immunohistochemical NOTCH1 and HES1 expression was jointly evaluated and correlated with other NOTCH1 targets, p21 (WAF1/Cip1) and Cyclin D1, using an unbiased cohort of 372 surgically treated HPV-negative HNSCC patients.
Membranous NOTCH1 expression was detected in 197 (61%) out of 324 evaluable tumor samples, and nuclear NOTCH1 expression in 91 samples (28%). Nuclear HES1 expression was found in 224 (67%) cases. Membranous and nuclear NOTCH1 expression were consistently and significantly correlated with nuclear HES1 (P < 0.001) and p21 (P = 0.03) expression, but not with Cyclin D1. NOTCH1 expression was significantly associated to early stages (I-II), non-recurrent disease, and better disease-specific (DSS) and overall survival (OS) rates (P < 0.001). Moreover, triple-positive cases (NOTCH1+/HES1+/p21+) exhibited significantly improved DSS (P < 0.001) and OS (P = 0.004), thus reinforcing the association of NOTCH pathway activation with a better prognosis in HNSCC. Multivariate analysis further revealed membranous NOTCH1 expression as a robust independent predictor of better DSS (HR = 0.554; 95% IC 0.412–0.745; P < 0.001) and better OS (HR = 0.640; 95% CI 0.491–0.835; P = 0.001).
These findings show the association of NOTCH pathway activation with a better prognosis in HNSCC patients, also revealing membranous NOTCH1 expression as a robust independent predictor of improved survival. Accordingly, these results suggest a tumor suppressive rather than an oncogenic role for NOTCH pathway in HNSCC.</abstract><pub>Elsevier Ltd</pub><doi>10.1016/j.oraloncology.2020.105003</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Head and neck squamous cell carcinoma HES1 NOTCH1 Prognosis Survival |
| title | Impact of notch signaling on the prognosis of patients with head and neck squamous cell carcinoma |
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