High Tumoral KPNA2 Expression Is a Potential Biomarker for Poor Prognosis in Advanced Neuroblastoma Patients - Research Article

Sep 23, 2026

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KPNA2 is a nuclear transport protein implicated in cancer aggressiveness and treatment resistance, yet its clinical significance in neuroblastoma had not been clarified. Using immunohistochemical staining, KPNA2 expression was assessed in 81 resected neuroblastoma specimens. Tumoral nuclear KPNA2 was present in neuroblastoma cells, and high KPNA2 predicted worse outcomes in nonradically resected patients. Database validation confirmed the association with poor prognosis in large cohorts, supporting KPNA2 as a prognostic indicator and potential therapeutic target.

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5: 1-7 (2025) doi: 10.21873/cdp.10404 High Tumoral KPNA2 Expression Is a Potential Biomarker for Poor Prognosis in Advanced Neuroblastoma Patients SAYAKA OTAKE 1* , KENJIRO OGUSHI 1* , GENDENSUREN DORJKHORLOO 1* , TAKEHIKO YOKOBORI2 , AKIRA NISHI3 , HIROYUKI KUWANO 1 , HIROSHI SAEKI 1 and KEN SHIRABE 1 1Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan; 2Division of Gene Therapy Science, Gunma University, Initiative for Advanced Research (GIAR), Maebashi, Japan; 3Department of Surgery, Gunma Children’s Medical Center, Shibukawa, Japan Abstract. Background/Aim: Karyopherin alpha 2 (KPNA2) has been reported to be associated with cancer aggressiveness and treatment resistance via transporting several cargo proteins into the nucleus, such as cancer-promoting E2F and DNA repair-related MRN complex. Recent studies have highlighted the KPNA2 functions in tumorigenesis and the progression of various cancers. However, the importance of KPNA2 expression has yet to be elucidated in clinical neuroblastoma patients. This study aimed to analyze the clinical impact of KPNA2 expression in neuroblastoma. Materials and Methods: KPNA2 expression in 81 resected neuroblastoma sections was examined using immunohistochemical staining. The significance and prognostic value of tumoral KPNA2 expression were analyzed using our cohort and R2 database. Results: The KPNA2 was expressed in the nucleus of neuroblastoma cells. The expression level of nuclear KPNA2 was not associated with clinicopathological factors in neuroblastoma. Among our cohort (n=81), nonradically resected neuroblastoma patients (n=37) with high KPNA2 expression had poorer prognoses than those with low *These Authors contributed equally to this study. Correspondence to: Takehiko Yokobori (ORCID: 0000-0003-3284- 4796), MD, Ph.D. , Division of Gene Therapy Science, Gunma University Initiative for Advanced Research (GIAR), 3-39-22 Showamachi, Maebashi 371-8511 Japan. Tel: +81 0272208022, Fax: +81 0272208230, e-mail: [bori45@gunma-u.ac.jp](bori45@gunma-u.ac.jp) [Key Words:](Key Words: Neuroblastoma)[ Neuroblastoma](Key Words: Neuroblastoma) , importin, prognostic markers. ©2025 The Author(s) . Published by the International Institute of Anticancer Research. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license ([https://creativecommons.org/licenses/by-nc-nd/4.0](https://creativecommons.org/licenses/by-nc-nd/4.0)). KPNA2 expression. The R2 database analysis validated that the high KPNA2 expression was related to the poor prognosis in the large-scale neuroblastoma cohort. Conclusion: KPNA2 expression evaluation in neuroblastoma is a promising indicator of prognosis in non-curative resected cases. KPNA2 targeting may be a promising therapeutic strategy against advanced neuroblastoma. Neuroblastoma is one of the most common extracranial solid tumors in pediatric patients. Several critical factors, such as MYCN (proto-oncogene BHLH transcription factor) amplification and copy number variations, are essential for diagnosing high-risk neuroblastoma (1, 2) . These molecular markers have been pivotal in identifying high-risk patients who require more aggressive treatments (3) . However, despite the implementation of multidisciplinary treatment strategies, the prognosis for high-risk neuroblastoma patients remains dismal. Therefore, developing new biomarkers is crucial for diagnosing tumor aggressiveness correctly and selecting a suitable therapeutic strategy against neuroblastoma. Karyopherin subunit alpha 2 (KPNA2), a nuclear transport protein, has been implicated in cancer aggressiveness of various cancers through the nuclear translocation of several oncogenic proteins (4, 5) . Notably, KPNA2 facilitates the nuclear import of cancer-related proteins such as E2F, a crucial regulator of the cell cycle, and the MRN c

FAQs

What was the study’s main goal regarding KPNA2 in neuroblastoma?

To clarify the clinical significance and prognostic value of tumoral KPNA2 expression in clinical neuroblastoma patients.

How was KPNA2 expression measured in the neuroblastoma samples?

KPNA2 expression was examined by immunohistochemical staining in 81 resected neuroblastoma sections.

Does tumoral KPNA2 expression relate to prognosis?

High nuclear KPNA2 expression was associated with poorer prognosis in nonradically resected patients, and R2 database analysis supported this finding in a large-scale cohort.

Sep 23, 2026

Uploaded by Jiven