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 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.
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Tuya
T
Bai
Research Program for Omics-based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma 3718511, Japan.
Takehiko
T
Yokobori
Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Bolag
B
Altan
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Munenori
M
Ide
Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, kawagoe, saitama 3508550, Japan.
Erito
E
Mochiki
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Mitsuhiro
M
Yanai
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Akiharu
A
Kimura
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Norimichi
N
Kogure
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Toru
T
Yanoma
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Masaki
M
Suzuki
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Pinjie
P
Bao
Department of Oncology Clinical Development, Gunma University, Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Kyoichi
K
Kaira
Big Data Center for Integrative Analysis, Gunma University Initiative for Advance Research (GIAR), Maebashi, Gunma 3718511, Japan.
Takayuki
T
Asao
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Ayaka
A
Katayama
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Tadashi
T
Handa
Department of Molecular Pharmacology and Oncology, Gunma University, Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Navchaa
N
Gombodorj
Research Program for Omics-based Medical Science, Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), Maebashi, Gunma 3718511, Japan.|Department of Molecular Pharmacology and Oncology, Gunma University, Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Masahiko
M
Nishiyama
Department of Diagnostic Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Tetsunari
T
Oyama
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Kyoichi
K
Ogata
Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Gunma 3718511, Japan.
Hiroyuki
H
Kuwano
D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D011379:Prognosis; D050777:Stathmin / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D014408:Biomarkers, Tumor; C493995:STMN1 protein, human; D050777:Stathmin; D017239:Paclitaxel