Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging

Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compa...
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Autor*in:	Vanarsa, Kamala [verfasserIn] Castillo, Jessica Wang, Long Lee, Kyung Hyun Pedroza, Claudia Lotan, Yair Mohan, Chandra

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Bladder cancer Proteomics Biomarkers Protein biomarkers Diagnostic biomarkers Surveillance biomarkers

Anmerkung:	© The Author(s) 2023

Übergeordnetes Werk:	Enthalten in: BMC medicine - London : BioMed Central, 2003, 21(2023), 1 vom: 05. Apr.
Übergeordnetes Werk:	volume:21 ; year:2023 ; number:1 ; day:05 ; month:04

Links:	Volltext

DOI / URN:	10.1186/s12916-023-02813-x

Katalog-ID:	SPR049947990

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245	1	0	\|a Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
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520			\|a Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test.
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650		4	\|a Protein biomarkers \|7 (dpeaa)DE-He213
650		4	\|a Diagnostic biomarkers \|7 (dpeaa)DE-He213
650		4	\|a Surveillance biomarkers \|7 (dpeaa)DE-He213
700	1		\|a Castillo, Jessica \|4 aut
700	1		\|a Wang, Long \|4 aut
700	1		\|a Lee, Kyung Hyun \|4 aut
700	1		\|a Pedroza, Claudia \|4 aut
700	1		\|a Lotan, Yair \|4 aut
700	1		\|a Mohan, Chandra \|4 aut
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allfields	10.1186/s12916-023-02813-x doi (DE-627)SPR049947990 (SPR)s12916-023-02813-x-e DE-627 ger DE-627 rakwb eng Vanarsa, Kamala verfasserin aut Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. Bladder cancer (dpeaa)DE-He213 Proteomics (dpeaa)DE-He213 Biomarkers (dpeaa)DE-He213 Protein biomarkers (dpeaa)DE-He213 Diagnostic biomarkers (dpeaa)DE-He213 Surveillance biomarkers (dpeaa)DE-He213 Castillo, Jessica aut Wang, Long aut Lee, Kyung Hyun aut Pedroza, Claudia aut Lotan, Yair aut Mohan, Chandra aut Enthalten in BMC medicine London : BioMed Central, 2003 21(2023), 1 vom: 05. Apr. (DE-627)377271225 (DE-600)2131669-7 1741-7015 nnns volume:21 year:2023 number:1 day:05 month:04 https://dx.doi.org/10.1186/s12916-023-02813-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 21 2023 1 05 04
spelling	10.1186/s12916-023-02813-x doi (DE-627)SPR049947990 (SPR)s12916-023-02813-x-e DE-627 ger DE-627 rakwb eng Vanarsa, Kamala verfasserin aut Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. Bladder cancer (dpeaa)DE-He213 Proteomics (dpeaa)DE-He213 Biomarkers (dpeaa)DE-He213 Protein biomarkers (dpeaa)DE-He213 Diagnostic biomarkers (dpeaa)DE-He213 Surveillance biomarkers (dpeaa)DE-He213 Castillo, Jessica aut Wang, Long aut Lee, Kyung Hyun aut Pedroza, Claudia aut Lotan, Yair aut Mohan, Chandra aut Enthalten in BMC medicine London : BioMed Central, 2003 21(2023), 1 vom: 05. Apr. (DE-627)377271225 (DE-600)2131669-7 1741-7015 nnns volume:21 year:2023 number:1 day:05 month:04 https://dx.doi.org/10.1186/s12916-023-02813-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 21 2023 1 05 04
allfields_unstemmed	10.1186/s12916-023-02813-x doi (DE-627)SPR049947990 (SPR)s12916-023-02813-x-e DE-627 ger DE-627 rakwb eng Vanarsa, Kamala verfasserin aut Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. Bladder cancer (dpeaa)DE-He213 Proteomics (dpeaa)DE-He213 Biomarkers (dpeaa)DE-He213 Protein biomarkers (dpeaa)DE-He213 Diagnostic biomarkers (dpeaa)DE-He213 Surveillance biomarkers (dpeaa)DE-He213 Castillo, Jessica aut Wang, Long aut Lee, Kyung Hyun aut Pedroza, Claudia aut Lotan, Yair aut Mohan, Chandra aut Enthalten in BMC medicine London : BioMed Central, 2003 21(2023), 1 vom: 05. Apr. (DE-627)377271225 (DE-600)2131669-7 1741-7015 nnns volume:21 year:2023 number:1 day:05 month:04 https://dx.doi.org/10.1186/s12916-023-02813-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 21 2023 1 05 04
allfieldsGer	10.1186/s12916-023-02813-x doi (DE-627)SPR049947990 (SPR)s12916-023-02813-x-e DE-627 ger DE-627 rakwb eng Vanarsa, Kamala verfasserin aut Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. Bladder cancer (dpeaa)DE-He213 Proteomics (dpeaa)DE-He213 Biomarkers (dpeaa)DE-He213 Protein biomarkers (dpeaa)DE-He213 Diagnostic biomarkers (dpeaa)DE-He213 Surveillance biomarkers (dpeaa)DE-He213 Castillo, Jessica aut Wang, Long aut Lee, Kyung Hyun aut Pedroza, Claudia aut Lotan, Yair aut Mohan, Chandra aut Enthalten in BMC medicine London : BioMed Central, 2003 21(2023), 1 vom: 05. Apr. (DE-627)377271225 (DE-600)2131669-7 1741-7015 nnns volume:21 year:2023 number:1 day:05 month:04 https://dx.doi.org/10.1186/s12916-023-02813-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 21 2023 1 05 04
allfieldsSound	10.1186/s12916-023-02813-x doi (DE-627)SPR049947990 (SPR)s12916-023-02813-x-e DE-627 ger DE-627 rakwb eng Vanarsa, Kamala verfasserin aut Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2023 Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. Bladder cancer (dpeaa)DE-He213 Proteomics (dpeaa)DE-He213 Biomarkers (dpeaa)DE-He213 Protein biomarkers (dpeaa)DE-He213 Diagnostic biomarkers (dpeaa)DE-He213 Surveillance biomarkers (dpeaa)DE-He213 Castillo, Jessica aut Wang, Long aut Lee, Kyung Hyun aut Pedroza, Claudia aut Lotan, Yair aut Mohan, Chandra aut Enthalten in BMC medicine London : BioMed Central, 2003 21(2023), 1 vom: 05. Apr. (DE-627)377271225 (DE-600)2131669-7 1741-7015 nnns volume:21 year:2023 number:1 day:05 month:04 https://dx.doi.org/10.1186/s12916-023-02813-x kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 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 21 2023 1 05 04
language	English
source	Enthalten in BMC medicine 21(2023), 1 vom: 05. Apr. volume:21 year:2023 number:1 day:05 month:04
sourceStr	Enthalten in BMC medicine 21(2023), 1 vom: 05. Apr. volume:21 year:2023 number:1 day:05 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Bladder cancer Proteomics Biomarkers Protein biomarkers Diagnostic biomarkers Surveillance biomarkers
isfreeaccess_bool	true
container_title	BMC medicine
authorswithroles_txt_mv	Vanarsa, Kamala @@aut@@ Castillo, Jessica @@aut@@ Wang, Long @@aut@@ Lee, Kyung Hyun @@aut@@ Pedroza, Claudia @@aut@@ Lotan, Yair @@aut@@ Mohan, Chandra @@aut@@
publishDateDaySort_date	2023-04-05T00:00:00Z
hierarchy_top_id	377271225
id	SPR049947990
language_de	englisch
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The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. 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author	Vanarsa, Kamala
spellingShingle	Vanarsa, Kamala misc Bladder cancer misc Proteomics misc Biomarkers misc Protein biomarkers misc Diagnostic biomarkers misc Surveillance biomarkers Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
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topic_title	Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging Bladder cancer (dpeaa)DE-He213 Proteomics (dpeaa)DE-He213 Biomarkers (dpeaa)DE-He213 Protein biomarkers (dpeaa)DE-He213 Diagnostic biomarkers (dpeaa)DE-He213 Surveillance biomarkers (dpeaa)DE-He213
topic	misc Bladder cancer misc Proteomics misc Biomarkers misc Protein biomarkers misc Diagnostic biomarkers misc Surveillance biomarkers
topic_unstemmed	misc Bladder cancer misc Proteomics misc Biomarkers misc Protein biomarkers misc Diagnostic biomarkers misc Surveillance biomarkers
topic_browse	misc Bladder cancer misc Proteomics misc Biomarkers misc Protein biomarkers misc Diagnostic biomarkers misc Surveillance biomarkers
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title	Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
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title_full	Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
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author_browse	Vanarsa, Kamala Castillo, Jessica Wang, Long Lee, Kyung Hyun Pedroza, Claudia Lotan, Yair Mohan, Chandra
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author-letter	Vanarsa, Kamala
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title_sort	comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
title_auth	Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
abstract	Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. © The Author(s) 2023
abstractGer	Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. © The Author(s) 2023
abstract_unstemmed	Background Bladder cancer (BC) is among the most common cancers diagnosed in men in the USA. The current gold standards for the diagnosis of BC are invasive or lack the sensitivity to correctly identify the disease. Methods An aptamer-based screen analyzed the expression of 1317 proteins in BC compared to urology clinic controls. The top hits were subjected to systems biology analyses. Next, 30 urine proteins were ELISA-validated in an independent cohort of 68 subjects. Three of these proteins were next validated in an independent BC cohort of differing ethnicity. Results Systems biology analysis implicated molecular functions related to the extracellular matrix, collagen, integrin, heparin, and transmembrane tyrosine kinase signaling in BC susceptibility, with HNF4A and NFKB1 emerging as key molecular regulators. STEM analysis of the dysregulated pathways implicated a functional role for the immune system, complement, and interleukins in BC disease progression. Of 21 urine proteins that discriminated BC from urology clinic controls (UC), urine d-dimer displayed the highest accuracy (0.96) and sensitivity of 97%. Furthermore, 8 urine proteins significantly discriminated MIBC from NMIBC (AUC = 0.75–0.99), with IL-8 and IgA being the best performers. Urine IgA and fibronectin exhibited the highest specificity of 80% at fixed sensitivity for identifying advanced BC. Conclusions Given the high sensitivity (97%) of urine d-dimer for BC, it may have a role in the initial diagnosis or detection of cancer recurrence. On the other hand, urine IL-8 and IgA may have the potential in identifying disease progression during patient follow-up. The use of these biomarkers for initial triage could have a significant impact as the current cystoscopy-based diagnostic and surveillance approach is costly and invasive when compared to a simple urine test. © The Author(s) 2023
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title_short	Comprehensive proteomics and platform validation of urinary biomarkers for bladder cancer diagnosis and staging
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author2	Castillo, Jessica Wang, Long Lee, Kyung Hyun Pedroza, Claudia Lotan, Yair Mohan, Chandra
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