High Tumoral STMN1 Expression Is Associated with Malignant Potential and Poor Prognosis in Patients with Neuroblastoma

Author:

Ogushi Kenjiro1ORCID,Yokobori Takehiko12ORCID,Nobusawa Sumihito3,Shirakura Takahiro3,Hirato Junko4,Erkhem-Ochir Bilguun2,Okami Haruka1,Dorjkhorloo Gendensuren1,Nishi Akira5,Suzuki Makoto16ORCID,Otake Sayaka1,Saeki Hiroshi1,Shirabe Ken1

Affiliation:

1. Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan

2. Division of Integrated Oncology Research, Initiative for Advanced Research (GIAR), Gunma University, Maebashi 371-8511, Japan

3. Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi 371-8510, Japan

4. Department of Pathology, Public Tomioka General Hospital, Tomioka 370-2393, Japan

5. Department of Surgery, Gunma Children’s Medical Center, Shibukawa 377-8577, Japan

6. Department of Surgery, Iwate Medical University School of Medicine, Morioka 028-3895, Japan

Abstract

Background. Stathmin 1 (STMN1), a marker for immature neurons and tumors, controls microtubule dynamics by destabilizing tubulin. It plays an essential role in cancer progression and indicates poor prognosis in several cancers. This potential protein has not been clarified in clinical patients with neuroblastoma. Therefore, this study aimed to assess the clinical significance and STMN1 function in neuroblastoma with and without MYCN amplification. Methods. Using immunohistochemical staining, STMN1 expression was examined in 81 neuroblastoma samples. Functional analysis revealed the association among STMN1 suppression, cellular viability, and endogenous or exogenous MYCN expression in neuroblastoma cell lines. Result. High levels of STMN1 expression were associated with malignant potential, proliferation potency, and poor prognosis in neuroblastoma. STMN1 expression was an independent prognostic factor in patients with neuroblastoma. Furthermore, STMN1 knockdown inhibited neuroblastoma cell growth regardless of endogenous and exogenous MYCN overexpression. Conclusion. Our data suggest that assessing STMN1 expression in neuroblastoma could be a powerful indicator of prognosis and that STMN1 might be a promising therapeutic candidate against refractory neuroblastoma with and without MYCN amplification.

Funder

Japan Society for the Promotion of Science

GIAR Linkage Grant 2022

Research Grant of the Princess Takamatsu Cancer Research Fund

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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