The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance
Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression...
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| Veröffentlicht in: | Virchows Archiv : an international journal of pathology 2014-07, Vol.465 (1), p.25-33 |
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| creator | Tapia, Oscar Riquelme, Ismael Leal, Pamela Sandoval, Alejandra Aedo, Susana Weber, Helga Letelier, Pablo Bellolio, Enrique Villaseca, Miguel Garcia, Patricia Roa, Juan Carlos |
| description | Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval,
p
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| doi_str_mv | 10.1007/s00428-014-1588-4 |
| format | Article |
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p
< 0.05). For survival analyses, the Kaplan–Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (
p
= 0.02) and tumors with lymph node metastases (
p
< 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (
p
= 0.03). Moreover, PI3K (
p
= 0.004), AKT (
p
= 0.01), p-AKT (
p
= 0.01), P70S6K1 (
p
= 0.04), p-P70S6K1 (
p
= 0.001), and eIF-4E (
p
= 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (
p
= 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.</description><identifier>ISSN: 0945-6317</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s00428-014-1588-4</identifier><identifier>PMID: 24844205</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adaptor Proteins, Signal Transducing - biosynthesis ; Aged ; Case-Control Studies ; Deregulation ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphatic Metastasis - physiopathology ; Male ; Medicine ; Medicine & Public Health ; Middle Aged ; Original Article ; Pathology ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphoproteins - biosynthesis ; Prognosis ; Proto-Oncogene Proteins c-akt - metabolism ; Signal Transduction ; Stomach Neoplasms - mortality ; Stomach Neoplasms - pathology ; Stomach Neoplasms - physiopathology ; TOR Serine-Threonine Kinases - metabolism ; Tumors</subject><ispartof>Virchows Archiv : an international journal of pathology, 2014-07, Vol.465 (1), p.25-33</ispartof><rights>Springer-Verlag Berlin Heidelberg 2014</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c405t-510b63f20e36a6e07efea48d89631c0768bb4278968b4b8ad4c984b8fec32c903</citedby><cites>FETCH-LOGICAL-c405t-510b63f20e36a6e07efea48d89631c0768bb4278968b4b8ad4c984b8fec32c903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00428-014-1588-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00428-014-1588-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24844205$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tapia, Oscar</creatorcontrib><creatorcontrib>Riquelme, Ismael</creatorcontrib><creatorcontrib>Leal, Pamela</creatorcontrib><creatorcontrib>Sandoval, Alejandra</creatorcontrib><creatorcontrib>Aedo, Susana</creatorcontrib><creatorcontrib>Weber, Helga</creatorcontrib><creatorcontrib>Letelier, Pablo</creatorcontrib><creatorcontrib>Bellolio, Enrique</creatorcontrib><creatorcontrib>Villaseca, Miguel</creatorcontrib><creatorcontrib>Garcia, Patricia</creatorcontrib><creatorcontrib>Roa, Juan Carlos</creatorcontrib><title>The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance</title><title>Virchows Archiv : an international journal of pathology</title><addtitle>Virchows Arch</addtitle><addtitle>Virchows Arch</addtitle><description>Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval,
p
< 0.05). For survival analyses, the Kaplan–Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (
p
= 0.02) and tumors with lymph node metastases (
p
< 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (
p
= 0.03). Moreover, PI3K (
p
= 0.004), AKT (
p
= 0.01), p-AKT (
p
= 0.01), P70S6K1 (
p
= 0.04), p-P70S6K1 (
p
= 0.001), and eIF-4E (
p
= 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (
p
= 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.</description><subject>Adaptor Proteins, Signal Transducing - biosynthesis</subject><subject>Aged</subject><subject>Case-Control Studies</subject><subject>Deregulation</subject><subject>Female</subject><subject>Humans</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphatic Metastasis - physiopathology</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Original Article</subject><subject>Pathology</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphoproteins - biosynthesis</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Signal Transduction</subject><subject>Stomach Neoplasms - mortality</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - physiopathology</subject><subject>TOR Serine-Threonine Kinases - 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Academic</collection><jtitle>Virchows Archiv : an international journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tapia, Oscar</au><au>Riquelme, Ismael</au><au>Leal, Pamela</au><au>Sandoval, Alejandra</au><au>Aedo, Susana</au><au>Weber, Helga</au><au>Letelier, Pablo</au><au>Bellolio, Enrique</au><au>Villaseca, Miguel</au><au>Garcia, Patricia</au><au>Roa, Juan Carlos</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance</atitle><jtitle>Virchows Archiv : an international journal of pathology</jtitle><stitle>Virchows Arch</stitle><addtitle>Virchows Arch</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>465</volume><issue>1</issue><spage>25</spage><epage>33</epage><pages>25-33</pages><issn>0945-6317</issn><eissn>1432-2307</eissn><abstract>Signaling pathway alterations are important in the development of gastric cancer (GC). Deregulation of the PI3K/AKT/mTOR pathway plays a crucial role in the regulation of multiple cellular functions including cell growth, proliferation, metabolism, and angiogenesis. Our goal was to assess expression of proteins involved in the PI3K/AKT/mTOR pathway by immunohistochemistry (IHC) in tumor and nontumor gastric mucosa from patients with advanced GC. We evaluated 71 tumor and 71 nontumor gastric mucosa samples from advanced GC patients, selected from Hernán Henríquez Aravena Hospital (Temuco, Chile). The targets studied were PI3K, AKT, p-AKT, PTEN, mTOR, p-mTOR, P70S6K1, p-P70S6K1, 4E-BP1, p-4E-BP1, eIF4E, and p-eIF4E. Expression data were correlated with clinicomorphological data. Descriptive and analytical statistics were used (95 % confidence interval,
p
< 0.05). For survival analyses, the Kaplan–Meier method and the log-rank test were used. PI3K, AKT, p-AKT, p-mTOR, p-4E-BP1, P70S6K1, p-P70S6K1, eIF-4E, and p-eIF-4E proteins were significantly overexpressed in tumor tissue. Conversely, PTEN was underexpressed in tumor tissue, notably in pT3-pT4 tumors (
p
= 0.02) and tumors with lymph node metastases (
p
< 0.001). P70S6K1 expression was associated with pT3-pT4 tumors (
p
= 0.03). Moreover, PI3K (
p
= 0.004), AKT (
p
= 0.01), p-AKT (
p
= 0.01), P70S6K1 (
p
= 0.04), p-P70S6K1 (
p
= 0.001), and eIF-4E (
p
= 0.004) were overexpressed in tumors with lymph node metastases. Low expression of 4E-BP1 was associated with poor overall survival (
p
= 0.03). Our results suggest that the PI3K/AKT/mTOR pathway is activated in GC, with overexpression in tumor tissue of most of the studied proteins (total and phosphorylated). These might be considered as target for specific targeted therapy in GC.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>24844205</pmid><doi>10.1007/s00428-014-1588-4</doi><tpages>9</tpages></addata></record> |
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| ispartof | Virchows Archiv : an international journal of pathology, 2014-07, Vol.465 (1), p.25-33 |
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| language | eng |
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| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Adaptor Proteins, Signal Transducing - biosynthesis Aged Case-Control Studies Deregulation Female Humans Kaplan-Meier Estimate Lymphatic Metastasis - physiopathology Male Medicine Medicine & Public Health Middle Aged Original Article Pathology Phosphatidylinositol 3-Kinases - metabolism Phosphoproteins - biosynthesis Prognosis Proto-Oncogene Proteins c-akt - metabolism Signal Transduction Stomach Neoplasms - mortality Stomach Neoplasms - pathology Stomach Neoplasms - physiopathology TOR Serine-Threonine Kinases - metabolism Tumors |
| title | The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance |
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