High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients
| Autor: | Mitsuhiro Yanai, Munenori Ide, Norimichi Kogure, Pinjie Bao, Kyoichi Kaira, Takehiko Yokobori, Navchaa Gombodorj, Bolag Altan, Hiroyuki Kuwano, Tadashi Handa, Tetsunari Oyama, Ayaka Katayama, Masaki Suzuki, Toru Yanoma, Erito Mochiki, Akiharu Kimura, Masahiko Nishiyama, Kyoichi Ogata, Tuya Bai, Takayuki Asao |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Paclitaxel Colorectal cancer Apoptosis Kaplan-Meier Estimate 03 medical and health sciences Prostate cancer chemistry.chemical_compound 0302 clinical medicine Breast cancer Stomach Neoplasms Internal medicine medicine Adjuvant therapy Biomarkers Tumor Humans Lung cancer Aged Cell Proliferation business.industry gastric cancer Cancer Middle Aged poor prognosis medicine.disease Prognosis Stathmin1 Gene Expression Regulation Neoplastic chemosensitivity 030104 developmental biology chemistry Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer cell Stathmin Female business Translational Therapeutics |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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