KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma

Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have grea...
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Gespeichert in:

Autor*in:	Hua He [verfasserIn] Lu Liang [verfasserIn] Jingjing Huang [verfasserIn] Shiyao Jiang [verfasserIn] Yueying Liu [verfasserIn] Xiaoyan Sun [verfasserIn] Yi Li [verfasserIn] Li Cong [verfasserIn] Yiqun Jiang [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A

Übergeordnetes Werk:	In: Frontiers in Pharmacology - Frontiers Media S.A., 2010, 13(2022)
Übergeordnetes Werk:	volume:13 ; year:2022

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fphar.2022.1007429

Katalog-ID:	DOAJ084895993

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520			\|a Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target.
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allfields	10.3389/fphar.2022.1007429 doi (DE-627)DOAJ084895993 (DE-599)DOAJdcdf245db76748968c5d8d612de8f1e6 DE-627 ger DE-627 rakwb eng RM1-950 Hua He verfasserin aut KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target. lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A Therapeutics. Pharmacology Hua He verfasserin aut Lu Liang verfasserin aut Lu Liang verfasserin aut Jingjing Huang verfasserin aut Jingjing Huang verfasserin aut Shiyao Jiang verfasserin aut Shiyao Jiang verfasserin aut Yueying Liu verfasserin aut Yueying Liu verfasserin aut Xiaoyan Sun verfasserin aut Xiaoyan Sun verfasserin aut Yi Li verfasserin aut Yi Li verfasserin aut Li Cong verfasserin aut Li Cong verfasserin aut Yiqun Jiang verfasserin aut Yiqun Jiang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.1007429 kostenfrei https://doaj.org/article/dcdf245db76748968c5d8d612de8f1e6 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.1007429/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 13 2022
spelling	10.3389/fphar.2022.1007429 doi (DE-627)DOAJ084895993 (DE-599)DOAJdcdf245db76748968c5d8d612de8f1e6 DE-627 ger DE-627 rakwb eng RM1-950 Hua He verfasserin aut KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target. lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A Therapeutics. Pharmacology Hua He verfasserin aut Lu Liang verfasserin aut Lu Liang verfasserin aut Jingjing Huang verfasserin aut Jingjing Huang verfasserin aut Shiyao Jiang verfasserin aut Shiyao Jiang verfasserin aut Yueying Liu verfasserin aut Yueying Liu verfasserin aut Xiaoyan Sun verfasserin aut Xiaoyan Sun verfasserin aut Yi Li verfasserin aut Yi Li verfasserin aut Li Cong verfasserin aut Li Cong verfasserin aut Yiqun Jiang verfasserin aut Yiqun Jiang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.1007429 kostenfrei https://doaj.org/article/dcdf245db76748968c5d8d612de8f1e6 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.1007429/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 13 2022
allfields_unstemmed	10.3389/fphar.2022.1007429 doi (DE-627)DOAJ084895993 (DE-599)DOAJdcdf245db76748968c5d8d612de8f1e6 DE-627 ger DE-627 rakwb eng RM1-950 Hua He verfasserin aut KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target. lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A Therapeutics. Pharmacology Hua He verfasserin aut Lu Liang verfasserin aut Lu Liang verfasserin aut Jingjing Huang verfasserin aut Jingjing Huang verfasserin aut Shiyao Jiang verfasserin aut Shiyao Jiang verfasserin aut Yueying Liu verfasserin aut Yueying Liu verfasserin aut Xiaoyan Sun verfasserin aut Xiaoyan Sun verfasserin aut Yi Li verfasserin aut Yi Li verfasserin aut Li Cong verfasserin aut Li Cong verfasserin aut Yiqun Jiang verfasserin aut Yiqun Jiang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.1007429 kostenfrei https://doaj.org/article/dcdf245db76748968c5d8d612de8f1e6 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.1007429/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 13 2022
allfieldsGer	10.3389/fphar.2022.1007429 doi (DE-627)DOAJ084895993 (DE-599)DOAJdcdf245db76748968c5d8d612de8f1e6 DE-627 ger DE-627 rakwb eng RM1-950 Hua He verfasserin aut KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target. lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A Therapeutics. Pharmacology Hua He verfasserin aut Lu Liang verfasserin aut Lu Liang verfasserin aut Jingjing Huang verfasserin aut Jingjing Huang verfasserin aut Shiyao Jiang verfasserin aut Shiyao Jiang verfasserin aut Yueying Liu verfasserin aut Yueying Liu verfasserin aut Xiaoyan Sun verfasserin aut Xiaoyan Sun verfasserin aut Yi Li verfasserin aut Yi Li verfasserin aut Li Cong verfasserin aut Li Cong verfasserin aut Yiqun Jiang verfasserin aut Yiqun Jiang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.1007429 kostenfrei https://doaj.org/article/dcdf245db76748968c5d8d612de8f1e6 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.1007429/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 13 2022
allfieldsSound	10.3389/fphar.2022.1007429 doi (DE-627)DOAJ084895993 (DE-599)DOAJdcdf245db76748968c5d8d612de8f1e6 DE-627 ger DE-627 rakwb eng RM1-950 Hua He verfasserin aut KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target. lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A Therapeutics. Pharmacology Hua He verfasserin aut Lu Liang verfasserin aut Lu Liang verfasserin aut Jingjing Huang verfasserin aut Jingjing Huang verfasserin aut Shiyao Jiang verfasserin aut Shiyao Jiang verfasserin aut Yueying Liu verfasserin aut Yueying Liu verfasserin aut Xiaoyan Sun verfasserin aut Xiaoyan Sun verfasserin aut Yi Li verfasserin aut Yi Li verfasserin aut Li Cong verfasserin aut Li Cong verfasserin aut Yiqun Jiang verfasserin aut Yiqun Jiang verfasserin aut In Frontiers in Pharmacology Frontiers Media S.A., 2010 13(2022) (DE-627)642889392 (DE-600)2587355-6 16639812 nnns volume:13 year:2022 https://doi.org/10.3389/fphar.2022.1007429 kostenfrei https://doaj.org/article/dcdf245db76748968c5d8d612de8f1e6 kostenfrei https://www.frontiersin.org/articles/10.3389/fphar.2022.1007429/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 13 2022
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callnumber-first	R - Medicine
author	Hua He
spellingShingle	Hua He misc RM1-950 misc lung adenocarcinoma misc gemcitabine misc ferroptosis misc synergistic effect misc risk model misc KIF20A misc Therapeutics. Pharmacology KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma
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topic_title	RM1-950 KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma lung adenocarcinoma gemcitabine ferroptosis synergistic effect risk model KIF20A
topic	misc RM1-950 misc lung adenocarcinoma misc gemcitabine misc ferroptosis misc synergistic effect misc risk model misc KIF20A misc Therapeutics. Pharmacology
topic_unstemmed	misc RM1-950 misc lung adenocarcinoma misc gemcitabine misc ferroptosis misc synergistic effect misc risk model misc KIF20A misc Therapeutics. Pharmacology
topic_browse	misc RM1-950 misc lung adenocarcinoma misc gemcitabine misc ferroptosis misc synergistic effect misc risk model misc KIF20A misc Therapeutics. Pharmacology
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title	KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma
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title_full	KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma
author_sort	Hua He
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title_sort	kif20a is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma
callnumber	RM1-950
title_auth	KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma
abstract	Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target.
abstractGer	Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target.
abstract_unstemmed	Gemcitabine (GEM), an antimetabolite that terminates DNA synthesis, is commonly used in the treatment of cancers including lung adenocarcinoma (LUAD). However, downregulation of sensitivity limits the therapeutic effect. Ferroptosis as the new form of regulated cell death has been shown to have great potential for cancer treatment with chemoresistance. Here, three genes with both ferroptosis and GEM-response-associated features were screened from RNA sequencing and public data for constructing an independent risk model. LUAD patients with different risk scores had differences in mutational landscape, gene enrichment pathways, and drug sensitivity. By Cell Counting Kit-8 assay, flow cytometry, and colony forming assay, we demonstrate that GEM and ferroptosis inducer (FIN) imidazole Ketone Erastin had a synergistic combined anti-proliferative effect on LUAD cells and knockdown of KIF20A (the core gene of our model) further enhanced cell death in vitro by inducing ferroptosis. In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target.
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title_short	KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma
url	https://doi.org/10.3389/fphar.2022.1007429 https://doaj.org/article/dcdf245db76748968c5d8d612de8f1e6 https://www.frontiersin.org/articles/10.3389/fphar.2022.1007429/full https://doaj.org/toc/1663-9812
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In conclusion, we identified a link between ferroptosis and GEM response in LUAD cells and developed a robust signature that can effectively classify LUAD patients into subgroups with different overall survival. For LUAD, the combined treatment modality of GEM and FIN is potentially effective and KIF20A may be a new therapeutic target.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">lung adenocarcinoma</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">gemcitabine</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">ferroptosis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">synergistic effect</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">risk model</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">KIF20A</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Therapeutics. 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KIF20A is associated with clinical prognosis and synergistic effect of gemcitabine combined with ferroptosis inducer in lung adenocarcinoma

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