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High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients

BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to inves...

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Autores principales: Bai, Tuya, Yokobori, Takehiko, Altan, Bolag, Ide, Munenori, Mochiki, Erito, Yanai, Mitsuhiro, Kimura, Akiharu, Kogure, Norimichi, Yanoma, Toru, Suzuki, Masaki, Bao, Pinjie, Kaira, Kyoichi, Asao, Takayuki, Katayama, Ayaka, Handa, Tadashi, Gombodorj, Navchaa, Nishiyama, Masahiko, Oyama, Tetsunari, Ogata, Kyoichi, Kuwano, Hiroyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418450/
https://www.ncbi.nlm.nih.gov/pubmed/28334732
http://dx.doi.org/10.1038/bjc.2017.76
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author Bai, Tuya
Yokobori, Takehiko
Altan, Bolag
Ide, Munenori
Mochiki, Erito
Yanai, Mitsuhiro
Kimura, Akiharu
Kogure, Norimichi
Yanoma, Toru
Suzuki, Masaki
Bao, Pinjie
Kaira, Kyoichi
Asao, Takayuki
Katayama, Ayaka
Handa, Tadashi
Gombodorj, Navchaa
Nishiyama, Masahiko
Oyama, Tetsunari
Ogata, Kyoichi
Kuwano, Hiroyuki
author_facet Bai, Tuya
Yokobori, Takehiko
Altan, Bolag
Ide, Munenori
Mochiki, Erito
Yanai, Mitsuhiro
Kimura, Akiharu
Kogure, Norimichi
Yanoma, Toru
Suzuki, Masaki
Bao, Pinjie
Kaira, Kyoichi
Asao, Takayuki
Katayama, Ayaka
Handa, Tadashi
Gombodorj, Navchaa
Nishiyama, Masahiko
Oyama, Tetsunari
Ogata, Kyoichi
Kuwano, Hiroyuki
author_sort Bai, Tuya
collection PubMed
description BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines. RESULTS: Multivariate and Kaplan–Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis. CONCLUSIONS: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.
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spelling pubmed-54184502018-04-25 High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients Bai, Tuya Yokobori, Takehiko Altan, Bolag Ide, Munenori Mochiki, Erito Yanai, Mitsuhiro Kimura, Akiharu Kogure, Norimichi Yanoma, Toru Suzuki, Masaki Bao, Pinjie Kaira, Kyoichi Asao, Takayuki Katayama, Ayaka Handa, Tadashi Gombodorj, Navchaa Nishiyama, Masahiko Oyama, Tetsunari Ogata, Kyoichi Kuwano, Hiroyuki Br J Cancer Translational Therapeutics BACKGROUND: Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. Despite several reports, its roles in gastric cancer (GC) remain unclear owing to a lack of analyses of highly metastatic cases. This study aimed to investigate STMN1 as a prognostic and predictive indicator of response to paclitaxel therapy in patients with GC, including inoperable cases. METHODS: Immunohistochemical analysis of STMN1 was performed on both operable (n=95) and inoperable GC (n=61) samples. The roles of STMN1 in cancer cell proliferation and sensitivity to a microtubule-targeting drug, paclitaxel, were confirmed by knockdown experiments using GC cell lines. RESULTS: Multivariate and Kaplan–Meier analyses demonstrated that high STMN1 was predictive of poor prognosis in both the groups. In the operable cohort, STMN1 expression correlated with cancer curability, recurrence, and resistance to adjuvant therapy. A correlation with paclitaxel resistance was observed in inoperable cases. Knockdown of STMN1 in GC cell lines inhibited proliferation and sensitised the cells to paclitaxel by enhancing apoptosis. CONCLUSIONS: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC. Nature Publishing Group 2017-04-25 2017-03-23 /pmc/articles/PMC5418450/ /pubmed/28334732 http://dx.doi.org/10.1038/bjc.2017.76 Text en Copyright © 2017 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Translational Therapeutics
Bai, Tuya
Yokobori, Takehiko
Altan, Bolag
Ide, Munenori
Mochiki, Erito
Yanai, Mitsuhiro
Kimura, Akiharu
Kogure, Norimichi
Yanoma, Toru
Suzuki, Masaki
Bao, Pinjie
Kaira, Kyoichi
Asao, Takayuki
Katayama, Ayaka
Handa, Tadashi
Gombodorj, Navchaa
Nishiyama, Masahiko
Oyama, Tetsunari
Ogata, Kyoichi
Kuwano, Hiroyuki
High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
title High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
title_full High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
title_fullStr High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
title_full_unstemmed High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
title_short High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
title_sort high stmn1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418450/
https://www.ncbi.nlm.nih.gov/pubmed/28334732
http://dx.doi.org/10.1038/bjc.2017.76
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