Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Yuchun Niu [verfasserIn] Anqi Lin [verfasserIn] Peng Luo [verfasserIn] Weiliang Zhu [verfasserIn] Ting Wei [verfasserIn] Ruixiang Tang [verfasserIn] Linlang Guo [verfasserIn] Jian Zhang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 11(2020)
Übergeordnetes Werk:	volume:11 ; year:2020

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2020.01213

Katalog-ID:	DOAJ068811128

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520			\|a BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy.
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allfields	10.3389/fphar.2020.01213 doi (DE-627)DOAJ068811128 (DE-599)DOAJd968378969394847a0690288182fed23 DE-627 ger DE-627 rakwb eng RM1-950 Yuchun Niu verfasserin aut Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy. immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations Therapeutics. Pharmacology Anqi Lin verfasserin aut Peng Luo verfasserin aut Weiliang Zhu verfasserin aut Ting Wei verfasserin aut Ruixiang Tang verfasserin aut Linlang Guo verfasserin aut Jian Zhang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 11(2020) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:11 year:2020 https://doi.org/10.3389/fphar.2020.01213 kostenfrei https://doaj.org/article/d968378969394847a0690288182fed23 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2020.01213/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
spelling	10.3389/fphar.2020.01213 doi (DE-627)DOAJ068811128 (DE-599)DOAJd968378969394847a0690288182fed23 DE-627 ger DE-627 rakwb eng RM1-950 Yuchun Niu verfasserin aut Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy. immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations Therapeutics. Pharmacology Anqi Lin verfasserin aut Peng Luo verfasserin aut Weiliang Zhu verfasserin aut Ting Wei verfasserin aut Ruixiang Tang verfasserin aut Linlang Guo verfasserin aut Jian Zhang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 11(2020) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:11 year:2020 https://doi.org/10.3389/fphar.2020.01213 kostenfrei https://doaj.org/article/d968378969394847a0690288182fed23 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2020.01213/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfields_unstemmed	10.3389/fphar.2020.01213 doi (DE-627)DOAJ068811128 (DE-599)DOAJd968378969394847a0690288182fed23 DE-627 ger DE-627 rakwb eng RM1-950 Yuchun Niu verfasserin aut Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy. immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations Therapeutics. Pharmacology Anqi Lin verfasserin aut Peng Luo verfasserin aut Weiliang Zhu verfasserin aut Ting Wei verfasserin aut Ruixiang Tang verfasserin aut Linlang Guo verfasserin aut Jian Zhang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 11(2020) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:11 year:2020 https://doi.org/10.3389/fphar.2020.01213 kostenfrei https://doaj.org/article/d968378969394847a0690288182fed23 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2020.01213/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsGer	10.3389/fphar.2020.01213 doi (DE-627)DOAJ068811128 (DE-599)DOAJd968378969394847a0690288182fed23 DE-627 ger DE-627 rakwb eng RM1-950 Yuchun Niu verfasserin aut Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy. immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations Therapeutics. Pharmacology Anqi Lin verfasserin aut Peng Luo verfasserin aut Weiliang Zhu verfasserin aut Ting Wei verfasserin aut Ruixiang Tang verfasserin aut Linlang Guo verfasserin aut Jian Zhang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 11(2020) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:11 year:2020 https://doi.org/10.3389/fphar.2020.01213 kostenfrei https://doaj.org/article/d968378969394847a0690288182fed23 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2020.01213/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
allfieldsSound	10.3389/fphar.2020.01213 doi (DE-627)DOAJ068811128 (DE-599)DOAJd968378969394847a0690288182fed23 DE-627 ger DE-627 rakwb eng RM1-950 Yuchun Niu verfasserin aut Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy. immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations Therapeutics. Pharmacology Anqi Lin verfasserin aut Peng Luo verfasserin aut Weiliang Zhu verfasserin aut Ting Wei verfasserin aut Ruixiang Tang verfasserin aut Linlang Guo verfasserin aut Jian Zhang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 11(2020) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:11 year:2020 https://doi.org/10.3389/fphar.2020.01213 kostenfrei https://doaj.org/article/d968378969394847a0690288182fed23 kostenfrei https://www.frontiersin.org/article/10.3389/fphar.2020.01213/full kostenfrei https://doaj.org/toc/1663-9812 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2020
language	English
source	In Frontiers in Pharmacology 11(2020) volume:11 year:2020
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format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations Therapeutics. Pharmacology
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container_title	Frontiers in Pharmacology
authorswithroles_txt_mv	Yuchun Niu @@aut@@ Anqi Lin @@aut@@ Peng Luo @@aut@@ Weiliang Zhu @@aut@@ Ting Wei @@aut@@ Ruixiang Tang @@aut@@ Linlang Guo @@aut@@ Jian Zhang @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
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callnumber-first	R - Medicine
author	Yuchun Niu
spellingShingle	Yuchun Niu misc RM1-950 misc immune checkpoint inhibitors misc prognosis misc lung adenocarcinoma (LUAD) misc NTRK3 misc mutations misc Therapeutics. Pharmacology Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors
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topic_title	RM1-950 Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors immune checkpoint inhibitors prognosis lung adenocarcinoma (LUAD) NTRK3 mutations
topic	misc RM1-950 misc immune checkpoint inhibitors misc prognosis misc lung adenocarcinoma (LUAD) misc NTRK3 misc mutations misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc immune checkpoint inhibitors misc prognosis misc lung adenocarcinoma (LUAD) misc NTRK3 misc mutations misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc immune checkpoint inhibitors misc prognosis misc lung adenocarcinoma (LUAD) misc NTRK3 misc mutations misc Therapeutics. Pharmacology
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title	Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors
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title_full	Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors
author_sort	Yuchun Niu
journal	Frontiers in Pharmacology
journalStr	Frontiers in Pharmacology
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author_browse	Yuchun Niu Anqi Lin Peng Luo Weiliang Zhu Ting Wei Ruixiang Tang Linlang Guo Jian Zhang
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author-letter	Yuchun Niu
doi_str_mv	10.3389/fphar.2020.01213
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title_sort	prognosis of lung adenocarcinoma patients with ntrk3 mutations to immune checkpoint inhibitors
callnumber	RM1-950
title_auth	Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors
abstract	BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy.
abstractGer	BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy.
abstract_unstemmed	BackgroundImmune checkpoint inhibitors (ICIs) are an important treatment modality that must be considered for patients with lung adenocarcinoma (LUAD). However, ICIs are effective only in some of these patients. Therefore, identifying biomarkers that accurately predict the prognosis of patients with LUAD treated with ICIs can help maximize their therapeutic benefits. This study aimed to identify a new potential predictor to better select and optimally benefit LUAD patients.MethodsWe first collected and analyzed a discovery immunotherapy cohort comprising clinical and mutation data for LUAD patients. Then, we evaluated whether the specific mutated genes can act as predictive biomarkers in this discovery immunotherapy cohort and further validated the findings in The Cancer Genome Atlas (TCGA) project LUAD cohort. Gene set enrichment analysis (GSEA) was used to explore possible alterations in DNA damage response (DDR) pathways within the gene mutation. Moreover, we analyzed whole-exome sequencing (WES) and drug sensitivity response data for LUAD cell lines in the Genomics of Drug Sensitivity in Cancer (GDSC) database.ResultsAmong the mutated genes screened from both the ICI treatment and TCGA-LUAD cohorts, NTRK3 mutation (mutant-type NTRK3, NTRK3-MT) was strongly associated with immunotherapy. First, significant differences in overall survival (OS) were observed between patients with NTRK3-MT and those with NTRK3-WT in the ICI treatment cohort but not in the non-ICI-treated TCGA-LUAD cohort. We then analyzed the association of NTRK3-MT with clinical characteristics and found the tumor mutation burden (TMB) to be significantly higher in both NTRK3-MT cohorts. However, significant differences in neoantigen levels and smoking history were found only for NTRK3-MT in the LUAD cohort from TCGA. Furthermore, some immune-related genes and immune cell-related genes were significantly upregulated in patients with NTRK3-MT compared to those with NTRK3-WT. In addition, NTRK3 mutation affected the deregulation of some signaling pathways and the DDR pathway.ConclusionsOur findings suggest that NTRK3-MT can predict the prognosis of patients with LUAD treated by ICIs and that it may have clinical significance for immunotherapy.
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title_short	Prognosis of Lung Adenocarcinoma Patients With NTRK3 Mutations to Immune Checkpoint Inhibitors
url	https://doi.org/10.3389/fphar.2020.01213 https://doaj.org/article/d968378969394847a0690288182fed23 https://www.frontiersin.org/article/10.3389/fphar.2020.01213/full https://doaj.org/toc/1663-9812
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author2	Anqi Lin Peng Luo Weiliang Zhu Ting Wei Ruixiang Tang Linlang Guo Jian Zhang
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up_date	2024-07-03T19:53:09.327Z
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