Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis
Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large...
Ausführliche Beschreibung
Autor*in: |
Abdo Alnabulsi [verfasserIn] Tiehui Wang [verfasserIn] Wei Pang [verfasserIn] Marius Ionescu [verfasserIn] Stephanie G Craig [verfasserIn] Matthew P Humphries [verfasserIn] Kris McCombe [verfasserIn] Manuel Salto Tellez [verfasserIn] Ayham Alnabulsi [verfasserIn] Graeme I Murray [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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In: The Journal of Pathology: Clinical Research - Wiley, 2016, 8(2022), 3, Seite 245-256 |
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Übergeordnetes Werk: |
volume:8 ; year:2022 ; number:3 ; pages:245-256 |
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DOI / URN: |
10.1002/cjp2.258 |
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Katalog-ID: |
DOAJ063530481 |
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520 | |a Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. | ||
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10.1002/cjp2.258 doi (DE-627)DOAJ063530481 (DE-599)DOAJf715cd1b985a4e41b854e404ec01f2b3 DE-627 ger DE-627 rakwb eng RB1-214 Abdo Alnabulsi verfasserin aut Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. biomarker colorectal cancer combinatorial analysis combinatorial algorithm immunohistochemistry prognosis Pathology Tiehui Wang verfasserin aut Wei Pang verfasserin aut Marius Ionescu verfasserin aut Stephanie G Craig verfasserin aut Matthew P Humphries verfasserin aut Kris McCombe verfasserin aut Manuel Salto Tellez verfasserin aut Ayham Alnabulsi verfasserin aut Graeme I Murray verfasserin aut In The Journal of Pathology: Clinical Research Wiley, 2016 8(2022), 3, Seite 245-256 (DE-627)820686514 (DE-600)2814357-7 20564538 nnns volume:8 year:2022 number:3 pages:245-256 https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/article/f715cd1b985a4e41b854e404ec01f2b3 kostenfrei https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/toc/2056-4538 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2022 3 245-256 |
spelling |
10.1002/cjp2.258 doi (DE-627)DOAJ063530481 (DE-599)DOAJf715cd1b985a4e41b854e404ec01f2b3 DE-627 ger DE-627 rakwb eng RB1-214 Abdo Alnabulsi verfasserin aut Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. biomarker colorectal cancer combinatorial analysis combinatorial algorithm immunohistochemistry prognosis Pathology Tiehui Wang verfasserin aut Wei Pang verfasserin aut Marius Ionescu verfasserin aut Stephanie G Craig verfasserin aut Matthew P Humphries verfasserin aut Kris McCombe verfasserin aut Manuel Salto Tellez verfasserin aut Ayham Alnabulsi verfasserin aut Graeme I Murray verfasserin aut In The Journal of Pathology: Clinical Research Wiley, 2016 8(2022), 3, Seite 245-256 (DE-627)820686514 (DE-600)2814357-7 20564538 nnns volume:8 year:2022 number:3 pages:245-256 https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/article/f715cd1b985a4e41b854e404ec01f2b3 kostenfrei https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/toc/2056-4538 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2022 3 245-256 |
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10.1002/cjp2.258 doi (DE-627)DOAJ063530481 (DE-599)DOAJf715cd1b985a4e41b854e404ec01f2b3 DE-627 ger DE-627 rakwb eng RB1-214 Abdo Alnabulsi verfasserin aut Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. biomarker colorectal cancer combinatorial analysis combinatorial algorithm immunohistochemistry prognosis Pathology Tiehui Wang verfasserin aut Wei Pang verfasserin aut Marius Ionescu verfasserin aut Stephanie G Craig verfasserin aut Matthew P Humphries verfasserin aut Kris McCombe verfasserin aut Manuel Salto Tellez verfasserin aut Ayham Alnabulsi verfasserin aut Graeme I Murray verfasserin aut In The Journal of Pathology: Clinical Research Wiley, 2016 8(2022), 3, Seite 245-256 (DE-627)820686514 (DE-600)2814357-7 20564538 nnns volume:8 year:2022 number:3 pages:245-256 https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/article/f715cd1b985a4e41b854e404ec01f2b3 kostenfrei https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/toc/2056-4538 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2022 3 245-256 |
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10.1002/cjp2.258 doi (DE-627)DOAJ063530481 (DE-599)DOAJf715cd1b985a4e41b854e404ec01f2b3 DE-627 ger DE-627 rakwb eng RB1-214 Abdo Alnabulsi verfasserin aut Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. biomarker colorectal cancer combinatorial analysis combinatorial algorithm immunohistochemistry prognosis Pathology Tiehui Wang verfasserin aut Wei Pang verfasserin aut Marius Ionescu verfasserin aut Stephanie G Craig verfasserin aut Matthew P Humphries verfasserin aut Kris McCombe verfasserin aut Manuel Salto Tellez verfasserin aut Ayham Alnabulsi verfasserin aut Graeme I Murray verfasserin aut In The Journal of Pathology: Clinical Research Wiley, 2016 8(2022), 3, Seite 245-256 (DE-627)820686514 (DE-600)2814357-7 20564538 nnns volume:8 year:2022 number:3 pages:245-256 https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/article/f715cd1b985a4e41b854e404ec01f2b3 kostenfrei https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/toc/2056-4538 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2022 3 245-256 |
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10.1002/cjp2.258 doi (DE-627)DOAJ063530481 (DE-599)DOAJf715cd1b985a4e41b854e404ec01f2b3 DE-627 ger DE-627 rakwb eng RB1-214 Abdo Alnabulsi verfasserin aut Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. biomarker colorectal cancer combinatorial analysis combinatorial algorithm immunohistochemistry prognosis Pathology Tiehui Wang verfasserin aut Wei Pang verfasserin aut Marius Ionescu verfasserin aut Stephanie G Craig verfasserin aut Matthew P Humphries verfasserin aut Kris McCombe verfasserin aut Manuel Salto Tellez verfasserin aut Ayham Alnabulsi verfasserin aut Graeme I Murray verfasserin aut In The Journal of Pathology: Clinical Research Wiley, 2016 8(2022), 3, Seite 245-256 (DE-627)820686514 (DE-600)2814357-7 20564538 nnns volume:8 year:2022 number:3 pages:245-256 https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/article/f715cd1b985a4e41b854e404ec01f2b3 kostenfrei https://doi.org/10.1002/cjp2.258 kostenfrei https://doaj.org/toc/2056-4538 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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_171 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_636 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2022 3 245-256 |
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Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis |
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Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis |
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identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis |
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Identification of a prognostic signature in colorectal cancer using combinatorial algorithm‐driven analysis |
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Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. |
abstractGer |
Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. |
abstract_unstemmed |
Abstract Colorectal carcinoma is one of the most common types of malignancy and a leading cause of cancer‐related death. Although clinicopathological parameters provide invaluable prognostic information, the accuracy of prognosis can be improved by using molecular biomarker signatures. Using a large dataset of immunohistochemistry‐based biomarkers (n = 66), this study has developed an effective methodology for identifying optimal biomarker combinations as a prognostic tool. Biomarkers were screened and assigned to related subsets before being analysed using an iterative algorithm customised for evaluating combinatorial interactions between biomarkers based on their combined statistical power. A signature consisting of six biomarkers was identified as the best combination in terms of prognostic power. The combination of biomarkers (STAT1, UCP1, p‐cofilin, LIMK2, FOXP3, and ICOS) was significantly associated with overall survival when computed as a linear variable (χ2 = 53.183, p < 0.001) and as a cluster variable (χ2 = 67.625, p < 0.001). This signature was also significantly independent of age, extramural vascular invasion, tumour stage, and lymph node metastasis (Wald = 32.898, p < 0.001). Assessment of the results in an external cohort showed that the signature was significantly associated with prognosis (χ2 = 14.217, p = 0.007). This study developed and optimised an innovative discovery approach which could be adapted for the discovery of biomarkers and molecular interactions in a range of biological and clinical studies. Furthermore, this study identified a protein signature that can be utilised as an independent prognostic method and for potential therapeutic interventions. |
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