Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model
Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction m...
Ausführliche Beschreibung
Autor*in: |
Yasunori Nishida [verfasserIn] Akiko Kawano Nagatsuma [verfasserIn] Motohiro Kojima [verfasserIn] Naoto Gotohda [verfasserIn] Atsushi Ochiai [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2020 |
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Übergeordnetes Werk: |
In: BMC Gastroenterology - BMC, 2003, 20(2020), 1, Seite 9 |
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Übergeordnetes Werk: |
volume:20 ; year:2020 ; number:1 ; pages:9 |
Links: |
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DOI / URN: |
10.1186/s12876-020-01556-w |
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Katalog-ID: |
DOAJ048788309 |
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520 | |a Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. | ||
650 | 4 | |a Pancreatic cancer | |
650 | 4 | |a Fibroblasts | |
650 | 4 | |a Tumor microenvironment | |
650 | 4 | |a Biomarkers | |
653 | 0 | |a Diseases of the digestive system. Gastroenterology | |
700 | 0 | |a Akiko Kawano Nagatsuma |e verfasserin |4 aut | |
700 | 0 | |a Motohiro Kojima |e verfasserin |4 aut | |
700 | 0 | |a Naoto Gotohda |e verfasserin |4 aut | |
700 | 0 | |a Atsushi Ochiai |e verfasserin |4 aut | |
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10.1186/s12876-020-01556-w doi (DE-627)DOAJ048788309 (DE-599)DOAJ4186c7cb3d524e6d92a3dd1374d3d472 DE-627 ger DE-627 rakwb eng RC799-869 Yasunori Nishida verfasserin aut Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. Pancreatic cancer Fibroblasts Tumor microenvironment Biomarkers Diseases of the digestive system. Gastroenterology Akiko Kawano Nagatsuma verfasserin aut Motohiro Kojima verfasserin aut Naoto Gotohda verfasserin aut Atsushi Ochiai verfasserin aut In BMC Gastroenterology BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643702 (DE-600)2041351-8 1471230X nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/article/4186c7cb3d524e6d92a3dd1374d3d472 kostenfrei https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/toc/1471-230X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 20 2020 1 9 |
spelling |
10.1186/s12876-020-01556-w doi (DE-627)DOAJ048788309 (DE-599)DOAJ4186c7cb3d524e6d92a3dd1374d3d472 DE-627 ger DE-627 rakwb eng RC799-869 Yasunori Nishida verfasserin aut Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. Pancreatic cancer Fibroblasts Tumor microenvironment Biomarkers Diseases of the digestive system. Gastroenterology Akiko Kawano Nagatsuma verfasserin aut Motohiro Kojima verfasserin aut Naoto Gotohda verfasserin aut Atsushi Ochiai verfasserin aut In BMC Gastroenterology BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643702 (DE-600)2041351-8 1471230X nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/article/4186c7cb3d524e6d92a3dd1374d3d472 kostenfrei https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/toc/1471-230X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 20 2020 1 9 |
allfields_unstemmed |
10.1186/s12876-020-01556-w doi (DE-627)DOAJ048788309 (DE-599)DOAJ4186c7cb3d524e6d92a3dd1374d3d472 DE-627 ger DE-627 rakwb eng RC799-869 Yasunori Nishida verfasserin aut Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. Pancreatic cancer Fibroblasts Tumor microenvironment Biomarkers Diseases of the digestive system. Gastroenterology Akiko Kawano Nagatsuma verfasserin aut Motohiro Kojima verfasserin aut Naoto Gotohda verfasserin aut Atsushi Ochiai verfasserin aut In BMC Gastroenterology BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643702 (DE-600)2041351-8 1471230X nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/article/4186c7cb3d524e6d92a3dd1374d3d472 kostenfrei https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/toc/1471-230X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 20 2020 1 9 |
allfieldsGer |
10.1186/s12876-020-01556-w doi (DE-627)DOAJ048788309 (DE-599)DOAJ4186c7cb3d524e6d92a3dd1374d3d472 DE-627 ger DE-627 rakwb eng RC799-869 Yasunori Nishida verfasserin aut Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. Pancreatic cancer Fibroblasts Tumor microenvironment Biomarkers Diseases of the digestive system. Gastroenterology Akiko Kawano Nagatsuma verfasserin aut Motohiro Kojima verfasserin aut Naoto Gotohda verfasserin aut Atsushi Ochiai verfasserin aut In BMC Gastroenterology BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643702 (DE-600)2041351-8 1471230X nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/article/4186c7cb3d524e6d92a3dd1374d3d472 kostenfrei https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/toc/1471-230X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 20 2020 1 9 |
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10.1186/s12876-020-01556-w doi (DE-627)DOAJ048788309 (DE-599)DOAJ4186c7cb3d524e6d92a3dd1374d3d472 DE-627 ger DE-627 rakwb eng RC799-869 Yasunori Nishida verfasserin aut Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. Pancreatic cancer Fibroblasts Tumor microenvironment Biomarkers Diseases of the digestive system. Gastroenterology Akiko Kawano Nagatsuma verfasserin aut Motohiro Kojima verfasserin aut Naoto Gotohda verfasserin aut Atsushi Ochiai verfasserin aut In BMC Gastroenterology BMC, 2003 20(2020), 1, Seite 9 (DE-627)326643702 (DE-600)2041351-8 1471230X nnns volume:20 year:2020 number:1 pages:9 https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/article/4186c7cb3d524e6d92a3dd1374d3d472 kostenfrei https://doi.org/10.1186/s12876-020-01556-w kostenfrei https://doaj.org/toc/1471-230X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ 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 20 2020 1 9 |
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Yasunori Nishida Akiko Kawano Nagatsuma Motohiro Kojima Naoto Gotohda Atsushi Ochiai |
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novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model |
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Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model |
abstract |
Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. |
abstractGer |
Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. |
abstract_unstemmed |
Abstract Background Stromal fibroblasts associated with pancreatic ductal adenocarcinoma (PDAC) play an important role in tumor progression through interactions with cancer cells. Our proposed combination strategies of in vitro and in silico biomarker screening through a cancer-stromal interaction model were previously identified several actin-binding proteins in human colon cancer stroma. The main aim of the present study was to identify novel prognostic markers in human PDAC stroma using our strategies. Methods Five primary cultivated fibroblasts from human pancreas were stimulated by two types of pancreatic cancer-cell-conditioned medium (Capan-1 and MIA PaCa-2) followed by gene expression analysis to identify up-regulated genes. Publicly available microarray data set concomitant with overall survival was collected and prognostic marker candidates were selected among the genes that were found to be up-regulated. The mRNA expression levels of the selected genes were evaluated in 5 human fresh PDAC tissues. Finally, survival analysis was performed based on immunohistochemical results on tissue microarrays consisting of 216 surgically resected PDAC tissues. Results The microarray data of the cancer-stromal interaction model revealed that 188 probes were significantly regulated in pancreatic fibroblasts. Further, six genes were selected using publicly available microarray data set, and a single Diaphanous-related formin-3 (DIAPH3), actin-binding protein, was identified as a stromal biomarker in PDAC fibroblasts by RNA validation analysis. DIAPH3 exhibited strong immunohistochemical expression in stromal fibroblasts. The high stromal expression of DIAPH3 was associated with shorter survival times of PDAC patients. Conclusions DIAPH3 was identified as a prognostic marker in PDAC fibroblasts using our biomarker screening strategies through the cancer-stromal interaction model, indicating that stromal actin-binding proteins might have an important biological role in cancer progression. These strategies were also available in PDAC, and can be used for stromal biomarker screening in various cancers. |
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Novel stromal biomarker screening in pancreatic cancer patients using the in vitro cancer-stromal interaction model |
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