Identification of Deleterious NOTCH Mutation as Novel Predictor to Efficacious Immunotherapy in NSCLC.
Identifieur interne : 000335 ( Main/Exploration ); précédent : 000334; suivant : 000336Identification of Deleterious NOTCH Mutation as Novel Predictor to Efficacious Immunotherapy in NSCLC.
Auteurs : Kai Zhang [République populaire de Chine] ; Xiaohua Hong [République populaire de Chine] ; Zhengbo Song [République populaire de Chine] ; Yu Xu [République populaire de Chine] ; Chengcheng Li [République populaire de Chine] ; Guoqiang Wang [République populaire de Chine] ; Yuzi Zhang [République populaire de Chine] ; Xiaochen Zhao [République populaire de Chine] ; Zhengyi Zhao [République populaire de Chine] ; Jing Zhao [République populaire de Chine] ; Mengli Huang [République populaire de Chine] ; Depei Huang [République populaire de Chine] ; Chuang Qi [République populaire de Chine] ; Chan Gao [République populaire de Chine] ; Shangli Cai [République populaire de Chine] ; Feifei Gu [République populaire de Chine] ; Yue Hu [République populaire de Chine] ; Chunwei Xu [République populaire de Chine] ; Wenxian Wang [République populaire de Chine] ; Zhenkun Lou [États-Unis] ; Yong Zhang ; Li LiuSource :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2020.
Abstract
PURPOSE
NOTCH signaling is associated with tumorigenesis, mutagenesis, and immune tolerance in non-small cell lung cancer (NSCLC), indicating its association with the clinical benefit of immune checkpoint inhibitors (ICI). We hypothesized that
EXPERIMENTAL DESIGN
Multiple-dimensional data including genomic, transcriptomic, and clinical data from cohorts of NSCLC internal and public cohorts involving immunotherapeutic patients were analyzed. Polymorphism Phenotyping v2 (PolyPhen-2) system was performed to determine deleterious
RESULTS
Our 3DMed cohort (
CONCLUSIONS
This work distinguishes del-
DOI: 10.1158/1078-0432.CCR-19-3976
PubMed: 32241817
Affiliations:
Links toward previous steps (curation, corpus...)
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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yuzi" sort="Zhang, Yuzi" uniqKey="Zhang Y" first="Yuzi" last="Zhang">Yuzi Zhang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Xiaochen" sort="Zhao, Xiaochen" uniqKey="Zhao X" first="Xiaochen" last="Zhao">Xiaochen Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Zhengyi" sort="Zhao, Zhengyi" uniqKey="Zhao Z" first="Zhengyi" last="Zhao">Zhengyi Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Jing" sort="Zhao, Jing" uniqKey="Zhao J" first="Jing" last="Zhao">Jing Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Mengli" sort="Huang, Mengli" uniqKey="Huang M" first="Mengli" last="Huang">Mengli Huang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Depei" sort="Huang, Depei" uniqKey="Huang D" first="Depei" last="Huang">Depei Huang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. 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China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Shangli" sort="Cai, Shangli" uniqKey="Cai S" first="Shangli" last="Cai">Shangli Cai</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gu, Feifei" sort="Gu, Feifei" uniqKey="Gu F" first="Feifei" last="Gu">Feifei Gu</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Yue" sort="Hu, Yue" uniqKey="Hu Y" first="Yue" last="Hu">Yue Hu</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Chunwei" sort="Xu, Chunwei" uniqKey="Xu C" first="Chunwei" last="Xu">Chunwei Xu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Wenxian" sort="Wang, Wenxian" uniqKey="Wang W" first="Wenxian" last="Wang">Wenxian Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang</wicri:regionArea><wicri:noRegion>Zhejiang</wicri:noRegion></affiliation></author><author><name sortKey="Lou, Zhenkun" sort="Lou, Zhenkun" uniqKey="Lou Z" first="Zhenkun" last="Lou">Zhenkun Lou</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, Mayo Clinic, Rochester, Minnesota. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Department of Oncology, Mayo Clinic, Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Zhang, Yong" sort="Zhang, Yong" uniqKey="Zhang Y" first="Yong" last="Zhang">Yong Zhang</name><affiliation><nlm:affiliation>Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</nlm:affiliation><wicri:noCountry code="subField">P.R.</wicri:noCountry></affiliation></author><author><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name><affiliation><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</nlm:affiliation><wicri:noCountry code="subField">P.R.</wicri:noCountry></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2020">2020</date><idno type="RBID">pubmed:32241817</idno><idno type="pmid">32241817</idno><idno type="doi">10.1158/1078-0432.CCR-19-3976</idno><idno type="wicri:Area/Main/Corpus">000368</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000368</idno><idno type="wicri:Area/Main/Curation">000368</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000368</idno><idno type="wicri:Area/Main/Exploration">000368</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Identification of Deleterious <i>NOTCH</i> Mutation as Novel Predictor to Efficacious Immunotherapy in NSCLC.</title><author><name sortKey="Zhang, Kai" sort="Zhang, Kai" uniqKey="Zhang K" first="Kai" last="Zhang">Kai Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Hong, Xiaohua" sort="Hong, Xiaohua" uniqKey="Hong X" first="Xiaohua" last="Hong">Xiaohua Hong</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Song, Zhengbo" sort="Song, Zhengbo" uniqKey="Song Z" first="Zhengbo" last="Song">Zhengbo Song</name><affiliation wicri:level="1"><nlm:affiliation>Zhejiang Cancer Hospital, Zhejiang, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Zhejiang Cancer Hospital, Zhejiang</wicri:regionArea><wicri:noRegion>Zhejiang</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Yu" sort="Xu, Yu" uniqKey="Xu Y" first="Yu" last="Xu">Yu Xu</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Li, Chengcheng" sort="Li, Chengcheng" uniqKey="Li C" first="Chengcheng" last="Li">Chengcheng Li</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Guoqiang" sort="Wang, Guoqiang" uniqKey="Wang G" first="Guoqiang" last="Wang">Guoqiang Wang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Yuzi" sort="Zhang, Yuzi" uniqKey="Zhang Y" first="Yuzi" last="Zhang">Yuzi Zhang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Xiaochen" sort="Zhao, Xiaochen" uniqKey="Zhao X" first="Xiaochen" last="Zhao">Xiaochen Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Zhengyi" sort="Zhao, Zhengyi" uniqKey="Zhao Z" first="Zhengyi" last="Zhao">Zhengyi Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Zhao, Jing" sort="Zhao, Jing" uniqKey="Zhao J" first="Jing" last="Zhao">Jing Zhao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Mengli" sort="Huang, Mengli" uniqKey="Huang M" first="Mengli" last="Huang">Mengli Huang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Depei" sort="Huang, Depei" uniqKey="Huang D" first="Depei" last="Huang">Depei Huang</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Qi, Chuang" sort="Qi, Chuang" uniqKey="Qi C" first="Chuang" last="Qi">Chuang Qi</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gao, Chan" sort="Gao, Chan" uniqKey="Gao C" first="Chan" last="Gao">Chan Gao</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Cai, Shangli" sort="Cai, Shangli" uniqKey="Cai S" first="Shangli" last="Cai">Shangli Cai</name><affiliation wicri:level="1"><nlm:affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>The Medical Department, 3D Medicines Inc., Shanghai</wicri:regionArea><wicri:noRegion>Shanghai</wicri:noRegion></affiliation></author><author><name sortKey="Gu, Feifei" sort="Gu, Feifei" uniqKey="Gu F" first="Feifei" last="Gu">Feifei Gu</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Hu, Yue" sort="Hu, Yue" uniqKey="Hu Y" first="Yue" last="Hu">Yue Hu</name><affiliation wicri:level="1"><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei</wicri:regionArea><wicri:noRegion>Hubei</wicri:noRegion></affiliation></author><author><name sortKey="Xu, Chunwei" sort="Xu, Chunwei" uniqKey="Xu C" first="Chunwei" last="Xu">Chunwei Xu</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian</wicri:regionArea><wicri:noRegion>Fujian</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Wenxian" sort="Wang, Wenxian" uniqKey="Wang W" first="Wenxian" last="Wang">Wenxian Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, P.R. China.</nlm:affiliation><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang</wicri:regionArea><wicri:noRegion>Zhejiang</wicri:noRegion></affiliation></author><author><name sortKey="Lou, Zhenkun" sort="Lou, Zhenkun" uniqKey="Lou Z" first="Zhenkun" last="Lou">Zhenkun Lou</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, Mayo Clinic, Rochester, Minnesota. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Minnesota</region></placeName><wicri:cityArea>Department of Oncology, Mayo Clinic, Rochester</wicri:cityArea></affiliation></author><author><name sortKey="Zhang, Yong" sort="Zhang, Yong" uniqKey="Zhang Y" first="Yong" last="Zhang">Yong Zhang</name><affiliation><nlm:affiliation>Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</nlm:affiliation><wicri:noCountry code="subField">P.R.</wicri:noCountry></affiliation></author><author><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name><affiliation><nlm:affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</nlm:affiliation><wicri:noCountry code="subField">P.R.</wicri:noCountry></affiliation></author></analytic><series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title><idno type="ISSN">1078-0432</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>PURPOSE</b></p><p>NOTCH signaling is associated with tumorigenesis, mutagenesis, and immune tolerance in non-small cell lung cancer (NSCLC), indicating its association with the clinical benefit of immune checkpoint inhibitors (ICI). We hypothesized that </p></div><div type="abstract" xml:lang="en"><p><b>EXPERIMENTAL DESIGN</b></p><p>Multiple-dimensional data including genomic, transcriptomic, and clinical data from cohorts of NSCLC internal and public cohorts involving immunotherapeutic patients were analyzed. Polymorphism Phenotyping v2 (PolyPhen-2) system was performed to determine deleterious </p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>Our 3DMed cohort (</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b></p><p>This work distinguishes del-</p></div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">32241817</PMID><DateRevised><Year>2020</Year><Month>07</Month><Day>16</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">1078-0432</ISSN><JournalIssue CitedMedium="Internet"><Volume>26</Volume><Issue>14</Issue><PubDate><Year>2020</Year><Month>Jul</Month><Day>15</Day></PubDate></JournalIssue><Title>Clinical cancer research : an official journal of the American Association for Cancer Research</Title><ISOAbbreviation>Clin Cancer Res</ISOAbbreviation></Journal><ArticleTitle>Identification of Deleterious <i>NOTCH</i> Mutation as Novel Predictor to Efficacious Immunotherapy in NSCLC.</ArticleTitle><Pagination><MedlinePgn>3649-3661</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1158/1078-0432.CCR-19-3976</ELocationID><Abstract><AbstractText Label="PURPOSE" NlmCategory="OBJECTIVE">NOTCH signaling is associated with tumorigenesis, mutagenesis, and immune tolerance in non-small cell lung cancer (NSCLC), indicating its association with the clinical benefit of immune checkpoint inhibitors (ICI). We hypothesized that <i>NOTCH</i> mutation in NSCLC might be a robust predictor of immunotherapeutic efficacy.</AbstractText><AbstractText Label="EXPERIMENTAL DESIGN" NlmCategory="METHODS">Multiple-dimensional data including genomic, transcriptomic, and clinical data from cohorts of NSCLC internal and public cohorts involving immunotherapeutic patients were analyzed. Polymorphism Phenotyping v2 (PolyPhen-2) system was performed to determine deleterious <i>NOTCH</i> mutation (del-<i>NOTCH</i><sup>mut</sup>). Further investigation on molecular mechanism was performed in The Cancer Genome Atlas (TCGA) data via CIBERSORT and gene set enrichment analysis.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Our 3DMed cohort (<i>n</i> = 58) and other four cohorts (Rizvi, POPLAR/OAK, Van Allen, and MSKCC; <i>n</i> = 1,499) uncovered marked correlation between <i>NOTCH1/2/3</i> mutation and better ICI outcomes in <i>EGFR/ALK</i><sup>WT</sup> population, including objective response rate (2.20-fold, <i>P</i> = 0.001), progression-free survival [HR, 0.61; 95% confidence interval (CI), 0.46-0.81; <i>P</i> = 0.001], and overall survival (HR, 0.56; 95% CI, 0.32-0.96; <i>P</i> = 0.035). Del-<i>NOTCH</i><sup>mut</sup> exhibited better predictive function than non-deleterious <i>NOTCH</i> mutation, potentially via greater transcription of genes related to DNA damage response and immune activation. Del-<i>NOTCH</i><sup>mut</sup> was not linked with prognosis in TCGA cohorts and chemotherapeutic response, but was independently associated with immunotherapeutic benefit, delineating the predictive, but not prognostic, utility of del-<i>NOTCH</i><sup>mut</sup>.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">This work distinguishes del-<i>NOTCH</i><sup>mut</sup> as a potential predictor to favorable ICI response in NSCLC, highlighting the importance of genomic profiling in immunotherapy. More importantly, our results unravel a possibility of personalized combination immunotherapy as adding NOTCH inhibitor to ICI regimen in NSCLC, for the optimization of ICI treatment in clinical practice.</AbstractText><CopyrightInformation>©2020 American Association for Cancer Research.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Zhang</LastName><ForeName>Kai</ForeName><Initials>K</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-7999-093X</Identifier><AffiliationInfo><Affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Hong</LastName><ForeName>Xiaohua</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Song</LastName><ForeName>Zhengbo</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Zhejiang Cancer Hospital, Zhejiang, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Xu</LastName><ForeName>Yu</ForeName><Initials>Y</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-6898-4307</Identifier><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Chengcheng</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Guoqiang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yuzi</ForeName><Initials>Y</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-7999-093X</Identifier><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Xiaochen</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Zhengyi</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhao</LastName><ForeName>Jing</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Mengli</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huang</LastName><ForeName>Depei</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Qi</LastName><ForeName>Chuang</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gao</LastName><ForeName>Chan</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cai</LastName><ForeName>Shangli</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>The Medical Department, 3D Medicines Inc., Shanghai, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gu</LastName><ForeName>Feifei</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hu</LastName><ForeName>Yue</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Chunwei</ForeName><Initials>C</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-6898-4307</Identifier><AffiliationInfo><Affiliation>Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Wenxian</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Zhejiang, P.R. China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lou</LastName><ForeName>Zhenkun</ForeName><Initials>Z</Initials><AffiliationInfo><Affiliation>Department of Oncology, Mayo Clinic, Rochester, Minnesota. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Yong</ForeName><Initials>Y</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-7999-093X</Identifier><AffiliationInfo><Affiliation>Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Li</ForeName><Initials>L</Initials><Identifier Source="ORCID">https://orcid.org/0000-0003-2314-8756</Identifier><AffiliationInfo><Affiliation>Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, P.R. China. liulixiehe2004@163.com lou.zhenkun@mayo.edu Zhang.Yong@mayo.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>04</Month><Day>02</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Clin Cancer Res</MedlineTA><NlmUniqueID>9502500</NlmUniqueID><ISSNLinking>1078-0432</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2019</Year><Month>12</Month><Day>04</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2020</Year><Month>02</Month><Day>13</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2020</Year><Month>03</Month><Day>30</Day></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2020</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2020</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2020</Year><Month>4</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">32241817</ArticleId><ArticleId IdType="pii">1078-0432.CCR-19-3976</ArticleId><ArticleId IdType="doi">10.1158/1078-0432.CCR-19-3976</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Minnesota</li></region></list><tree><noCountry><name sortKey="Liu, Li" sort="Liu, Li" uniqKey="Liu L" first="Li" last="Liu">Li Liu</name><name sortKey="Zhang, Yong" sort="Zhang, Yong" uniqKey="Zhang Y" first="Yong" last="Zhang">Yong Zhang</name></noCountry><country name="République populaire de Chine"><noRegion><name sortKey="Zhang, Kai" sort="Zhang, Kai" uniqKey="Zhang K" first="Kai" last="Zhang">Kai Zhang</name></noRegion><name sortKey="Cai, Shangli" sort="Cai, Shangli" uniqKey="Cai S" first="Shangli" last="Cai">Shangli Cai</name><name sortKey="Gao, Chan" sort="Gao, Chan" uniqKey="Gao C" first="Chan" last="Gao">Chan Gao</name><name sortKey="Gu, Feifei" sort="Gu, Feifei" uniqKey="Gu F" first="Feifei" last="Gu">Feifei Gu</name><name sortKey="Hong, Xiaohua" sort="Hong, Xiaohua" uniqKey="Hong X" first="Xiaohua" last="Hong">Xiaohua Hong</name><name sortKey="Hu, Yue" sort="Hu, Yue" uniqKey="Hu Y" first="Yue" last="Hu">Yue Hu</name><name sortKey="Huang, Depei" sort="Huang, Depei" uniqKey="Huang D" first="Depei" last="Huang">Depei Huang</name><name sortKey="Huang, Mengli" sort="Huang, Mengli" uniqKey="Huang M" first="Mengli" last="Huang">Mengli Huang</name><name sortKey="Li, Chengcheng" sort="Li, Chengcheng" uniqKey="Li C" first="Chengcheng" last="Li">Chengcheng Li</name><name sortKey="Qi, Chuang" sort="Qi, Chuang" uniqKey="Qi C" first="Chuang" last="Qi">Chuang Qi</name><name sortKey="Song, Zhengbo" sort="Song, Zhengbo" uniqKey="Song Z" first="Zhengbo" last="Song">Zhengbo Song</name><name sortKey="Wang, Guoqiang" sort="Wang, Guoqiang" uniqKey="Wang G" first="Guoqiang" last="Wang">Guoqiang Wang</name><name sortKey="Wang, Wenxian" sort="Wang, Wenxian" uniqKey="Wang W" first="Wenxian" last="Wang">Wenxian Wang</name><name sortKey="Xu, Chunwei" sort="Xu, Chunwei" uniqKey="Xu C" first="Chunwei" last="Xu">Chunwei Xu</name><name sortKey="Xu, Yu" sort="Xu, Yu" uniqKey="Xu Y" first="Yu" last="Xu">Yu Xu</name><name sortKey="Zhang, Yuzi" sort="Zhang, Yuzi" uniqKey="Zhang Y" first="Yuzi" last="Zhang">Yuzi Zhang</name><name sortKey="Zhao, Jing" sort="Zhao, Jing" uniqKey="Zhao J" first="Jing" last="Zhao">Jing Zhao</name><name sortKey="Zhao, Xiaochen" sort="Zhao, Xiaochen" uniqKey="Zhao X" first="Xiaochen" last="Zhao">Xiaochen Zhao</name><name sortKey="Zhao, Zhengyi" sort="Zhao, Zhengyi" uniqKey="Zhao Z" first="Zhengyi" last="Zhao">Zhengyi Zhao</name></country><country name="États-Unis"><region name="Minnesota"><name sortKey="Lou, Zhenkun" sort="Lou, Zhenkun" uniqKey="Lou Z" first="Zhenkun" last="Lou">Zhenkun Lou</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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