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肿瘤组织中高表达的KPNA2是晚期神经母细胞瘤患者预后不良的潜在生物标志物。

High Tumoral KPNA2 Expression Is a PotentialBiomarker for Poor Prognosis in Advanced Neuroblastoma Patients.

作者信息

Otake Sayaka, Ogushi Kenjiro, Dorjkhorloo Gendensuren, Yokobori Takehiko, Nishi Akira, Kuwano Hiroyuki, Saeki Hiroshi, Shirabe Ken

机构信息

Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.

Division of Gene Therapy Science, Gunma University, Initiative for Advanced Research (GIAR), Maebashi, Japan.

出版信息

Cancer Diagn Progn. 2025 Jan 3;5(1):1-7. doi: 10.21873/cdp.10404. eCollection 2025 Jan-Feb.

DOI:10.21873/cdp.10404
PMID:39758242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11696343/
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 immuno-histochemical 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), non-radically resected neuroblastoma patients (n=37) with high KPNA2 expression had poorer prognoses than those with low 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.

摘要

背景/目的:据报道,核转运蛋白α2(KPNA2)通过将几种货物蛋白转运到细胞核中,如促进癌症的E2F和DNA修复相关的MRN复合物,与癌症侵袭性和治疗耐药性相关。最近的研究强调了KPNA2在肿瘤发生和各种癌症进展中的作用。然而,KPNA2表达在临床神经母细胞瘤患者中的重要性尚未阐明。本研究旨在分析KPNA2表达在神经母细胞瘤中的临床影响。

材料与方法

采用免疫组织化学染色检测81例切除的神经母细胞瘤切片中KPNA2的表达。使用我们的队列和R2数据库分析肿瘤KPNA2表达的意义和预后价值。

结果

KPNA2在神经母细胞瘤细胞核中表达。神经母细胞瘤中细胞核KPNA2的表达水平与临床病理因素无关。在我们的队列(n = 81)中,KPNA2高表达的非根治性切除神经母细胞瘤患者(n = 37)的预后比KPNA2低表达的患者差。R2数据库分析证实,在大规模神经母细胞瘤队列中,KPNA2高表达与预后不良有关。

结论

神经母细胞瘤中KPNA2表达评估是未根治性切除病例预后的一个有前景的指标。靶向KPNA2可能是一种有前景的晚期神经母细胞瘤治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/f4996f186971/cdp-5-6-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/e3403e78aa71/cdp-5-3-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/682aedbe967b/cdp-5-4-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/f4996f186971/cdp-5-6-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/e3403e78aa71/cdp-5-3-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/682aedbe967b/cdp-5-4-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89ef/11696343/f4996f186971/cdp-5-6-g0001.jpg

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本文引用的文献

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Cancers (Basel). 2023 Sep 8;15(18):4482. doi: 10.3390/cancers15184482.
2
Novel roles of karyopherin subunit alpha 2 in hepatocellular carcinoma.核孔蛋白亚单位 α2 在肝细胞癌中的新作用。
Biomed Pharmacother. 2023 Jul;163:114792. doi: 10.1016/j.biopha.2023.114792. Epub 2023 Apr 28.
3
MiR-101-3p targets KPNA2 to inhibit the progression of lung squamous cell carcinoma cell lines.
微小RNA-101-3p靶向核转运蛋白α2以抑制肺鳞癌细胞系的进展。
Histol Histopathol. 2023 Oct;38(10):1169-1178. doi: 10.14670/HH-18-573. Epub 2022 Dec 13.
4
Prognostic analysis of E2F transcription factors E2F1 and E2F3 in four independent pediatric neuroblastoma cohorts.E2F 转录因子 E2F1 和 E2F3 在四个独立的小儿神经母细胞瘤队列中的预后分析。
BMC Pediatr. 2022 Jun 29;22(1):376. doi: 10.1186/s12887-022-03424-w.
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Neuroblastoma.神经母细胞瘤。
Pediatr Blood Cancer. 2021 May;68 Suppl 2(Suppl 2):e28473. doi: 10.1002/pbc.28473.
6
The emerging roles of KPNA2 in cancer.KPNA2 在癌症中的新兴作用。
Life Sci. 2020 Jan 15;241:117140. doi: 10.1016/j.lfs.2019.117140. Epub 2019 Dec 6.
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Jpn J Clin Oncol. 2018 Mar 1;48(3):214-241. doi: 10.1093/jjco/hyx176.
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Pancreatology. 2017 Jul-Aug;17(4):611-616. doi: 10.1016/j.pan.2017.04.011. Epub 2017 Apr 23.
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