Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas

Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and uro...
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Autor*in:	Kang, So Young [verfasserIn] Heo, You Jeong [verfasserIn] Kwon, Ghee Young [verfasserIn] Lee, Jeeyun [verfasserIn] Park, Se Hoon [verfasserIn] Kim, Kyoung-Mee [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial

Übergeordnetes Werk:	Enthalten in: Pathology, research and practice - München : Elsevier, 1978, 241
Übergeordnetes Werk:	volume:241

DOI / URN:	10.1016/j.prp.2022.154233

Katalog-ID:	ELV065216539

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245	1	0	\|a Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
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520			\|a Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas.
650		4	\|a Immune checkpoint inhibitors
650		4	\|a Prediction
650		4	\|a Biomarker
650		4	\|a CD274
650		4	\|a Gastric
650		4	\|a Urothelial
700	1		\|a Heo, You Jeong \|e verfasserin \|4 aut
700	1		\|a Kwon, Ghee Young \|e verfasserin \|4 aut
700	1		\|a Lee, Jeeyun \|e verfasserin \|4 aut
700	1		\|a Park, Se Hoon \|e verfasserin \|4 aut
700	1		\|a Kim, Kyoung-Mee \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|t Pathology, research and practice \|d München : Elsevier, 1978 \|g 241 \|h Online-Ressource \|w (DE-627)325789517 \|w (DE-600)2039756-2 \|w (DE-576)094480672 \|x 1618-0631 \|7 nnns
773	1	8	\|g volume:241
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912			\|a GBV_ILN_110
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912			\|a GBV_ILN_224
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2003
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912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2056
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912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4046
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
936	b	k	\|a 44.47 \|j Pathologie \|x Medizin \|q VZ
951			\|a AR
952			\|d 241

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publishDate	2022
allfields	10.1016/j.prp.2022.154233 doi (DE-627)ELV065216539 (ELSEVIER)S0344-0338(22)00477-0 DE-627 ger DE-627 rda eng 610 VZ 44.47 bkl Kang, So Young verfasserin aut Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas. Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial Heo, You Jeong verfasserin aut Kwon, Ghee Young verfasserin aut Lee, Jeeyun verfasserin aut Park, Se Hoon verfasserin aut Kim, Kyoung-Mee verfasserin aut Enthalten in Pathology, research and practice München : Elsevier, 1978 241 Online-Ressource (DE-627)325789517 (DE-600)2039756-2 (DE-576)094480672 1618-0631 nnns volume:241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.47 Pathologie Medizin VZ AR 241
spelling	10.1016/j.prp.2022.154233 doi (DE-627)ELV065216539 (ELSEVIER)S0344-0338(22)00477-0 DE-627 ger DE-627 rda eng 610 VZ 44.47 bkl Kang, So Young verfasserin aut Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas. Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial Heo, You Jeong verfasserin aut Kwon, Ghee Young verfasserin aut Lee, Jeeyun verfasserin aut Park, Se Hoon verfasserin aut Kim, Kyoung-Mee verfasserin aut Enthalten in Pathology, research and practice München : Elsevier, 1978 241 Online-Ressource (DE-627)325789517 (DE-600)2039756-2 (DE-576)094480672 1618-0631 nnns volume:241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.47 Pathologie Medizin VZ AR 241
allfields_unstemmed	10.1016/j.prp.2022.154233 doi (DE-627)ELV065216539 (ELSEVIER)S0344-0338(22)00477-0 DE-627 ger DE-627 rda eng 610 VZ 44.47 bkl Kang, So Young verfasserin aut Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas. Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial Heo, You Jeong verfasserin aut Kwon, Ghee Young verfasserin aut Lee, Jeeyun verfasserin aut Park, Se Hoon verfasserin aut Kim, Kyoung-Mee verfasserin aut Enthalten in Pathology, research and practice München : Elsevier, 1978 241 Online-Ressource (DE-627)325789517 (DE-600)2039756-2 (DE-576)094480672 1618-0631 nnns volume:241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.47 Pathologie Medizin VZ AR 241
allfieldsGer	10.1016/j.prp.2022.154233 doi (DE-627)ELV065216539 (ELSEVIER)S0344-0338(22)00477-0 DE-627 ger DE-627 rda eng 610 VZ 44.47 bkl Kang, So Young verfasserin aut Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas. Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial Heo, You Jeong verfasserin aut Kwon, Ghee Young verfasserin aut Lee, Jeeyun verfasserin aut Park, Se Hoon verfasserin aut Kim, Kyoung-Mee verfasserin aut Enthalten in Pathology, research and practice München : Elsevier, 1978 241 Online-Ressource (DE-627)325789517 (DE-600)2039756-2 (DE-576)094480672 1618-0631 nnns volume:241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.47 Pathologie Medizin VZ AR 241
allfieldsSound	10.1016/j.prp.2022.154233 doi (DE-627)ELV065216539 (ELSEVIER)S0344-0338(22)00477-0 DE-627 ger DE-627 rda eng 610 VZ 44.47 bkl Kang, So Young verfasserin aut Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas 2022 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas. Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial Heo, You Jeong verfasserin aut Kwon, Ghee Young verfasserin aut Lee, Jeeyun verfasserin aut Park, Se Hoon verfasserin aut Kim, Kyoung-Mee verfasserin aut Enthalten in Pathology, research and practice München : Elsevier, 1978 241 Online-Ressource (DE-627)325789517 (DE-600)2039756-2 (DE-576)094480672 1618-0631 nnns volume:241 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.47 Pathologie Medizin VZ AR 241
language	English
source	Enthalten in Pathology, research and practice 241 volume:241
sourceStr	Enthalten in Pathology, research and practice 241 volume:241
format_phy_str_mv	Article
bklname	Pathologie
institution	findex.gbv.de
topic_facet	Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial
dewey-raw	610
isfreeaccess_bool	false
container_title	Pathology, research and practice
authorswithroles_txt_mv	Kang, So Young @@aut@@ Heo, You Jeong @@aut@@ Kwon, Ghee Young @@aut@@ Lee, Jeeyun @@aut@@ Park, Se Hoon @@aut@@ Kim, Kyoung-Mee @@aut@@
publishDateDaySort_date	2022-01-01T00:00:00Z
hierarchy_top_id	325789517
dewey-sort	3610
id	ELV065216539
language_de	englisch
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author	Kang, So Young
spellingShingle	Kang, So Young ddc 610 bkl 44.47 misc Immune checkpoint inhibitors misc Prediction misc Biomarker misc CD274 misc Gastric misc Urothelial Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
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topic_title	610 VZ 44.47 bkl Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas Immune checkpoint inhibitors Prediction Biomarker CD274 Gastric Urothelial
topic	ddc 610 bkl 44.47 misc Immune checkpoint inhibitors misc Prediction misc Biomarker misc CD274 misc Gastric misc Urothelial
topic_unstemmed	ddc 610 bkl 44.47 misc Immune checkpoint inhibitors misc Prediction misc Biomarker misc CD274 misc Gastric misc Urothelial
topic_browse	ddc 610 bkl 44.47 misc Immune checkpoint inhibitors misc Prediction misc Biomarker misc CD274 misc Gastric misc Urothelial
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title	Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
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title_full	Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
author_sort	Kang, So Young
journal	Pathology, research and practice
journalStr	Pathology, research and practice
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author_browse	Kang, So Young Heo, You Jeong Kwon, Ghee Young Lee, Jeeyun Park, Se Hoon Kim, Kyoung-Mee
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title_sort	five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
title_auth	Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
abstract	Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas.
abstractGer	Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas.
abstract_unstemmed	Background: Ample evidence supports the potential of programmed death-ligand 1 (PD-L1) expression, detected by immunohistochemistry, as a predictive biomarker for immunotherapy in patients with advanced cancers. To predict the response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas, we aimed to replace PD-L1 combined positive score (CPS) with CD274 mRNA in the original four-gene signature and PD-L1 CPS model developed by us.Method: We used quantitative real-time polymerase chain reaction (qRT-PCR) to measure the expression levels of five target genes in a cohort of 49 patients (33 with gastric cancer and 16 with urothelial carcinoma) who had received immunotherapy and whose therapeutic responses were available. The predictive performance was evaluated using R package maxstat.Results: Cutoff values of mRNA expression level were measured using the log-rank statistics for progression-free survival (PFS). Based on these cutoffs, immunotherapy responses were predicted and sorted into responder (n = 12, 24.5%) and non-responder (n = 37, 75.5%) groups. The median PFS values of predicted responders and non-responders were 14.8 months (95% confidence interval [CI]: 0–34.7) and 4.7 months (95% CI: 1.0–8.4, p = 0.02), respectively. Among the 12 predicted responders, 10 had microsatellite-stable tumors with a low tumor mutational burden. The actual clinical responses (complete and partial) were higher in the responder group than those in the non-responder group: 83.3% and 16.2%, respectively.Conclusion: We modified a predictive biomarker for CD274 mRNA expression to predict the response to immunotherapy in patients with gastric or urothelial carcinomas.
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title_short	Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas
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author2	Heo, You Jeong Kwon, Ghee Young Lee, Jeeyun Park, Se Hoon Kim, Kyoung-Mee
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doi_str	10.1016/j.prp.2022.154233
up_date	2024-07-06T22:14:53.542Z
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Five-gene signature for the prediction of response to immune checkpoint inhibitors in patients with gastric and urothelial carcinomas

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