Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma

BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Xin Xu [verfasserIn] Yuming Wang [verfasserIn] Yongrui Bai [verfasserIn] Jun Lu [verfasserIn] Yuntao Guo [verfasserIn] Xiaohang Wang [verfasserIn] Ling Rong [verfasserIn] Jianmin Tang [verfasserIn] Xiumei Ma [verfasserIn] Jun Ma [verfasserIn] Lei Zhang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	ESCC radiotherapy NOTCH1 survival immune

Übergeordnetes Werk:	In: Frontiers in Immunology - Frontiers Media S.A., 2011, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fimmu.2022.1001173

Katalog-ID:	DOAJ023977132

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520			\|a BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.
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allfields	10.3389/fimmu.2022.1001173 doi (DE-627)DOAJ023977132 (DE-599)DOAJ0be1b2100f30458a9fe22f1882215b44 DE-627 ger DE-627 rakwb eng RC581-607 Xin Xu verfasserin aut Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC. ESCC radiotherapy NOTCH1 survival immune Immunologic diseases. Allergy Yuming Wang verfasserin aut Yongrui Bai verfasserin aut Jun Lu verfasserin aut Yuntao Guo verfasserin aut Xiaohang Wang verfasserin aut Ling Rong verfasserin aut Jianmin Tang verfasserin aut Xiumei Ma verfasserin aut Jun Ma verfasserin aut Lei Zhang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1001173 kostenfrei https://doaj.org/article/0be1b2100f30458a9fe22f1882215b44 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001173/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
spelling	10.3389/fimmu.2022.1001173 doi (DE-627)DOAJ023977132 (DE-599)DOAJ0be1b2100f30458a9fe22f1882215b44 DE-627 ger DE-627 rakwb eng RC581-607 Xin Xu verfasserin aut Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC. ESCC radiotherapy NOTCH1 survival immune Immunologic diseases. Allergy Yuming Wang verfasserin aut Yongrui Bai verfasserin aut Jun Lu verfasserin aut Yuntao Guo verfasserin aut Xiaohang Wang verfasserin aut Ling Rong verfasserin aut Jianmin Tang verfasserin aut Xiumei Ma verfasserin aut Jun Ma verfasserin aut Lei Zhang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1001173 kostenfrei https://doaj.org/article/0be1b2100f30458a9fe22f1882215b44 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001173/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfields_unstemmed	10.3389/fimmu.2022.1001173 doi (DE-627)DOAJ023977132 (DE-599)DOAJ0be1b2100f30458a9fe22f1882215b44 DE-627 ger DE-627 rakwb eng RC581-607 Xin Xu verfasserin aut Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC. ESCC radiotherapy NOTCH1 survival immune Immunologic diseases. Allergy Yuming Wang verfasserin aut Yongrui Bai verfasserin aut Jun Lu verfasserin aut Yuntao Guo verfasserin aut Xiaohang Wang verfasserin aut Ling Rong verfasserin aut Jianmin Tang verfasserin aut Xiumei Ma verfasserin aut Jun Ma verfasserin aut Lei Zhang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1001173 kostenfrei https://doaj.org/article/0be1b2100f30458a9fe22f1882215b44 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001173/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfieldsGer	10.3389/fimmu.2022.1001173 doi (DE-627)DOAJ023977132 (DE-599)DOAJ0be1b2100f30458a9fe22f1882215b44 DE-627 ger DE-627 rakwb eng RC581-607 Xin Xu verfasserin aut Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC. ESCC radiotherapy NOTCH1 survival immune Immunologic diseases. Allergy Yuming Wang verfasserin aut Yongrui Bai verfasserin aut Jun Lu verfasserin aut Yuntao Guo verfasserin aut Xiaohang Wang verfasserin aut Ling Rong verfasserin aut Jianmin Tang verfasserin aut Xiumei Ma verfasserin aut Jun Ma verfasserin aut Lei Zhang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1001173 kostenfrei https://doaj.org/article/0be1b2100f30458a9fe22f1882215b44 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001173/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
allfieldsSound	10.3389/fimmu.2022.1001173 doi (DE-627)DOAJ023977132 (DE-599)DOAJ0be1b2100f30458a9fe22f1882215b44 DE-627 ger DE-627 rakwb eng RC581-607 Xin Xu verfasserin aut Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC. ESCC radiotherapy NOTCH1 survival immune Immunologic diseases. Allergy Yuming Wang verfasserin aut Yongrui Bai verfasserin aut Jun Lu verfasserin aut Yuntao Guo verfasserin aut Xiaohang Wang verfasserin aut Ling Rong verfasserin aut Jianmin Tang verfasserin aut Xiumei Ma verfasserin aut Jun Ma verfasserin aut Lei Zhang verfasserin aut In Frontiers in Immunology Frontiers Media S.A., 2011 13(2022) (DE-627)657998354 (DE-600)2606827-8 16643224 nnns volume:13 year:2022 https://doi.org/10.3389/fimmu.2022.1001173 kostenfrei https://doaj.org/article/0be1b2100f30458a9fe22f1882215b44 kostenfrei https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001173/full kostenfrei https://doaj.org/toc/1664-3224 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 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 13 2022
language	English
source	In Frontiers in Immunology 13(2022) volume:13 year:2022
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topic_facet	ESCC radiotherapy NOTCH1 survival immune Immunologic diseases. Allergy
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container_title	Frontiers in Immunology
authorswithroles_txt_mv	Xin Xu @@aut@@ Yuming Wang @@aut@@ Yongrui Bai @@aut@@ Jun Lu @@aut@@ Yuntao Guo @@aut@@ Xiaohang Wang @@aut@@ Ling Rong @@aut@@ Jianmin Tang @@aut@@ Xiumei Ma @@aut@@ Jun Ma @@aut@@ Lei Zhang @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
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callnumber-first	R - Medicine
author	Xin Xu
spellingShingle	Xin Xu misc RC581-607 misc ESCC misc radiotherapy misc NOTCH1 misc survival misc immune misc Immunologic diseases. Allergy Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma
authorStr	Xin Xu
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topic_title	RC581-607 Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma ESCC radiotherapy NOTCH1 survival immune
topic	misc RC581-607 misc ESCC misc radiotherapy misc NOTCH1 misc survival misc immune misc Immunologic diseases. Allergy
topic_unstemmed	misc RC581-607 misc ESCC misc radiotherapy misc NOTCH1 misc survival misc immune misc Immunologic diseases. Allergy
topic_browse	misc RC581-607 misc ESCC misc radiotherapy misc NOTCH1 misc survival misc immune misc Immunologic diseases. Allergy
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title	Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma
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title_full	Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma
author_sort	Xin Xu
journal	Frontiers in Immunology
journalStr	Frontiers in Immunology
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author_browse	Xin Xu Yuming Wang Yongrui Bai Jun Lu Yuntao Guo Xiaohang Wang Ling Rong Jianmin Tang Xiumei Ma Jun Ma Lei Zhang
container_volume	13
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format_se	Elektronische Aufsätze
author-letter	Xin Xu
doi_str_mv	10.3389/fimmu.2022.1001173
author2-role	verfasserin
title_sort	identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma
callnumber	RC581-607
title_auth	Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma
abstract	BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.
abstractGer	BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.
abstract_unstemmed	BackgroundRadiotherapy plays an important effect on the standard therapy of esophageal squamous cell carcinoma (ESCC). However, the efficacy of the therapy is limited and a few patients do not achieve satisfactory treatment results due to the existence of radiation resistance. Therefore, it is necessary to identify the potential predictive biomarkers and treatment targets for ESCC.MethodsWe performed the whole-exome sequencing to determine the germline and somatic mutations in ESCC. Functional enrichment and pathway-based protein-protein interaction analyses were used to ascertain potential regulatory networks. Cell survival and cell death after treatment with radiotherapy were determined by CCK-8 and LDH release assays in ESCC cells. The correlations of NOTCH1 and tumor immune infiltration were also analyzed in ESCC.ResultsOur results showed that 344 somatic and 65 germline differentially mutated genes were detected to be radiosensitivity-related loci. The tumor mutational burdens (TMB) or microsatellite instability (MSI) were not significantly correlated with the response to radiotherapy in ESCC patients. Pathway-based protein-protein interaction analyses implied several hub genes with most nodes (such as PIK3CA, NOTCH1, STAT3 and KDR). The in vitro studies showed that the knockdown of NOTCH1 inhibited cell survival and rendered more cell death after the treatment with radiotherapy in ESCC cells, while NOTCH1 overexpression had the opposite effects. Moreover, NOTCH1, frequently up-regulated in ESCC, was negatively correlated with activated B cell and immature dendritic cell in ESCC. High expression of NOTCH1 was accompanied with the low levels of some immunotherapy-related cells, including CD8(+) T cells and NK cells.ConclusionsThese results indicate the differences of the germline mutations and somatic mutations between the radiosensitive and radioresistence groups in ESCC and imply that NOTCH1 plays important roles in regulating the radiosensitivity of ESCC. The findings might provide the biomarkers and potential treatment targets for improving the sensitivity to radiotherapy in ESCC.
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title_short	Identifying key mutations of radioresponsive genes in esophageal squamous cell carcinoma
url	https://doi.org/10.3389/fimmu.2022.1001173 https://doaj.org/article/0be1b2100f30458a9fe22f1882215b44 https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001173/full https://doaj.org/toc/1664-3224
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author2	Yuming Wang Yongrui Bai Jun Lu Yuntao Guo Xiaohang Wang Ling Rong Jianmin Tang Xiumei Ma Jun Ma Lei Zhang
author2Str	Yuming Wang Yongrui Bai Jun Lu Yuntao Guo Xiaohang Wang Ling Rong Jianmin Tang Xiumei Ma Jun Ma Lei Zhang
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