Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors
Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Lee, Su Jin [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2013 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag France 2013 |
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| Übergeordnetes Werk: |
Enthalten in: Targeted oncology - Paris : Springer Verlag France S.A.R.L., 2006, 8(2013), 4 vom: 01. Feb., Seite 271-280 |
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| Übergeordnetes Werk: |
volume:8 ; year:2013 ; number:4 ; day:01 ; month:02 ; pages:271-280 |
| Links: |
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| DOI / URN: |
10.1007/s11523-013-0253-1 |
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| Katalog-ID: |
SPR020531133 |
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| 245 | 1 | 0 | |a Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors |
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| 520 | |a Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. | ||
| 650 | 4 | |a Gastric cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PTCH1 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a SMO |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hedgehog pathway |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Prognosis |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Do, In-Gu |4 aut | |
| 700 | 1 | |a Lee, Jeeyun |4 aut | |
| 700 | 1 | |a Kim, Kyoung-Mee |4 aut | |
| 700 | 1 | |a Jang, Jiryeon |4 aut | |
| 700 | 1 | |a Sohn, Insuk |4 aut | |
| 700 | 1 | |a Kang, Won Ki |4 aut | |
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10.1007/s11523-013-0253-1 doi (DE-627)SPR020531133 (SPR)s11523-013-0253-1-e DE-627 ger DE-627 rakwb eng Lee, Su Jin verfasserin aut Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag France 2013 Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. Gastric cancer (dpeaa)DE-He213 PTCH1 (dpeaa)DE-He213 SMO (dpeaa)DE-He213 Hedgehog pathway (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Do, In-Gu aut Lee, Jeeyun aut Kim, Kyoung-Mee aut Jang, Jiryeon aut Sohn, Insuk aut Kang, Won Ki aut Enthalten in Targeted oncology Paris : Springer Verlag France S.A.R.L., 2006 8(2013), 4 vom: 01. Feb., Seite 271-280 (DE-627)507903838 (DE-600)2222136-0 1776-260X nnns volume:8 year:2013 number:4 day:01 month:02 pages:271-280 https://dx.doi.org/10.1007/s11523-013-0253-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 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_4393 GBV_ILN_4700 AR 8 2013 4 01 02 271-280 |
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10.1007/s11523-013-0253-1 doi (DE-627)SPR020531133 (SPR)s11523-013-0253-1-e DE-627 ger DE-627 rakwb eng Lee, Su Jin verfasserin aut Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag France 2013 Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. Gastric cancer (dpeaa)DE-He213 PTCH1 (dpeaa)DE-He213 SMO (dpeaa)DE-He213 Hedgehog pathway (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Do, In-Gu aut Lee, Jeeyun aut Kim, Kyoung-Mee aut Jang, Jiryeon aut Sohn, Insuk aut Kang, Won Ki aut Enthalten in Targeted oncology Paris : Springer Verlag France S.A.R.L., 2006 8(2013), 4 vom: 01. Feb., Seite 271-280 (DE-627)507903838 (DE-600)2222136-0 1776-260X nnns volume:8 year:2013 number:4 day:01 month:02 pages:271-280 https://dx.doi.org/10.1007/s11523-013-0253-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 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_4393 GBV_ILN_4700 AR 8 2013 4 01 02 271-280 |
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10.1007/s11523-013-0253-1 doi (DE-627)SPR020531133 (SPR)s11523-013-0253-1-e DE-627 ger DE-627 rakwb eng Lee, Su Jin verfasserin aut Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag France 2013 Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. Gastric cancer (dpeaa)DE-He213 PTCH1 (dpeaa)DE-He213 SMO (dpeaa)DE-He213 Hedgehog pathway (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Do, In-Gu aut Lee, Jeeyun aut Kim, Kyoung-Mee aut Jang, Jiryeon aut Sohn, Insuk aut Kang, Won Ki aut Enthalten in Targeted oncology Paris : Springer Verlag France S.A.R.L., 2006 8(2013), 4 vom: 01. Feb., Seite 271-280 (DE-627)507903838 (DE-600)2222136-0 1776-260X nnns volume:8 year:2013 number:4 day:01 month:02 pages:271-280 https://dx.doi.org/10.1007/s11523-013-0253-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 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_4393 GBV_ILN_4700 AR 8 2013 4 01 02 271-280 |
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10.1007/s11523-013-0253-1 doi (DE-627)SPR020531133 (SPR)s11523-013-0253-1-e DE-627 ger DE-627 rakwb eng Lee, Su Jin verfasserin aut Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag France 2013 Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. Gastric cancer (dpeaa)DE-He213 PTCH1 (dpeaa)DE-He213 SMO (dpeaa)DE-He213 Hedgehog pathway (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Do, In-Gu aut Lee, Jeeyun aut Kim, Kyoung-Mee aut Jang, Jiryeon aut Sohn, Insuk aut Kang, Won Ki aut Enthalten in Targeted oncology Paris : Springer Verlag France S.A.R.L., 2006 8(2013), 4 vom: 01. Feb., Seite 271-280 (DE-627)507903838 (DE-600)2222136-0 1776-260X nnns volume:8 year:2013 number:4 day:01 month:02 pages:271-280 https://dx.doi.org/10.1007/s11523-013-0253-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 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_4393 GBV_ILN_4700 AR 8 2013 4 01 02 271-280 |
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10.1007/s11523-013-0253-1 doi (DE-627)SPR020531133 (SPR)s11523-013-0253-1-e DE-627 ger DE-627 rakwb eng Lee, Su Jin verfasserin aut Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors 2013 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag France 2013 Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. Gastric cancer (dpeaa)DE-He213 PTCH1 (dpeaa)DE-He213 SMO (dpeaa)DE-He213 Hedgehog pathway (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 Do, In-Gu aut Lee, Jeeyun aut Kim, Kyoung-Mee aut Jang, Jiryeon aut Sohn, Insuk aut Kang, Won Ki aut Enthalten in Targeted oncology Paris : Springer Verlag France S.A.R.L., 2006 8(2013), 4 vom: 01. Feb., Seite 271-280 (DE-627)507903838 (DE-600)2222136-0 1776-260X nnns volume:8 year:2013 number:4 day:01 month:02 pages:271-280 https://dx.doi.org/10.1007/s11523-013-0253-1 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 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_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 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_4393 GBV_ILN_4700 AR 8 2013 4 01 02 271-280 |
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Enthalten in Targeted oncology 8(2013), 4 vom: 01. Feb., Seite 271-280 volume:8 year:2013 number:4 day:01 month:02 pages:271-280 |
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Enthalten in Targeted oncology 8(2013), 4 vom: 01. Feb., Seite 271-280 volume:8 year:2013 number:4 day:01 month:02 pages:271-280 |
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Lee, Su Jin @@aut@@ Do, In-Gu @@aut@@ Lee, Jeeyun @@aut@@ Kim, Kyoung-Mee @@aut@@ Jang, Jiryeon @@aut@@ Sohn, Insuk @@aut@@ Kang, Won Ki @@aut@@ |
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We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. 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|
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Lee, Su Jin |
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Lee, Su Jin misc Gastric cancer misc PTCH1 misc SMO misc Hedgehog pathway misc Prognosis Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors |
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Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors Gastric cancer (dpeaa)DE-He213 PTCH1 (dpeaa)DE-He213 SMO (dpeaa)DE-He213 Hedgehog pathway (dpeaa)DE-He213 Prognosis (dpeaa)DE-He213 |
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misc Gastric cancer misc PTCH1 misc SMO misc Hedgehog pathway misc Prognosis |
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misc Gastric cancer misc PTCH1 misc SMO misc Hedgehog pathway misc Prognosis |
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Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors |
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Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors |
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Lee, Su Jin Do, In-Gu Lee, Jeeyun Kim, Kyoung-Mee Jang, Jiryeon Sohn, Insuk Kang, Won Ki |
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gastric cancer (gc) patients with hedgehog pathway activation: ptch1 and gli2 as independent prognostic factors |
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Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors |
| abstract |
Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. © Springer-Verlag France 2013 |
| abstractGer |
Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. © Springer-Verlag France 2013 |
| abstract_unstemmed |
Abstract Activation of sonic hedgehog (HH) signaling pathway has been implicated in aggressiveness and progression of gastrointestinal tumors. We planned this study to identify a subgroup of gastric cancer (GC) patients with HH activation and to assess the effect of a HH inhibitor in HH activated GC in vitro. We surveyed HH pathway activation among 512 GC specimens for protein expression of various target genes involved in HH pathway: Indian hedgehog (IHH), patched-1 (PTCH1), smoothened (SMO), GLI2, and FOXA2. We analyzed the correlations between the expression of these factors and clinicopathological features and prognosis. In vitro, ten gastric cancer cell lines were screened for anti-tumoractivity of an HH inhibitor, GDC-0449. Among the 512 specimens, 105 (20.0 %), 83 (16.3 %), 130 (25.5 %), 61 (12.0 %), and 206 (40.8 %) were positive for IHH, PTCH1, GLI2, SMO, and FOXA2 expression, respectively. PTCH1 expression was more frequently observed in well- or moderately differentiated tubular adenocarcinoma, intestinal type and low stage GC. GLI2 was correlated with lymphovascular invasion and intestinal type GC. A high-stage and negative PTCH1 staining were identified as unfavorable independent risk factors for overall survival in multivariate analysis (P < 0.001, 0.045, respectively). For IHH, SMO, and FOXA2, there was no statistical difference in clinicopathologic variables and survival outcome. An HH inhibitor had particularly potent effects on GC cell lines with SMO mRNA overexpression. This is the largest report to analyze the hedgehog pathway in GC. PTCH1 overexpression was an independent prognostic factor for survival and SMO overexpression which was found in 12.0 % of GC patients might be the potential predictive marker of HH inhibitor. © Springer-Verlag France 2013 |
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| title_short |
Gastric cancer (GC) patients with hedgehog pathway activation: PTCH1 and GLI2 as independent prognostic factors |
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https://dx.doi.org/10.1007/s11523-013-0253-1 |
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Do, In-Gu Lee, Jeeyun Kim, Kyoung-Mee Jang, Jiryeon Sohn, Insuk Kang, Won Ki |
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10.1007/s11523-013-0253-1 |
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| score |
7.4010954 |