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High STMN1 level is associated with chemo-resistance and poor prognosis in gastric cancer patients.
- Source :
-
British journal of cancer [Br J Cancer] 2017 Apr 25; Vol. 116 (9), pp. 1177-1185. Date of Electronic Publication: 2017 Mar 23. - Publication Year :
- 2017
-
Abstract
- 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.<br />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.<br />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.<br />Conclusions: STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC.
- Subjects :
- Aged
Apoptosis drug effects
Cell Proliferation drug effects
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Paclitaxel administration & dosage
Prognosis
Stomach Neoplasms genetics
Stomach Neoplasms pathology
Biomarkers, Tumor genetics
Drug Resistance, Neoplasm genetics
Stathmin genetics
Stomach Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 116
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 28334732
- Full Text :
- https://doi.org/10.1038/bjc.2017.76