SRSF1表达增加预示多发性骨髓瘤预后不良。

Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma.

作者信息

Zhang Jiawei, Wang Zanzan, Wang Kailai, Xin Dijia, Wang Luyao, Fan Yili, Xu Yang

机构信息

Department of Hematology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

Zhejiang University Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.

出版信息

J Oncol. 2023 May 10;2023:9998927. doi: 10.1155/2023/9998927. eCollection 2023.

DOI:10.1155/2023/9998927

PMID:37206090

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10191755/

Abstract

BACKGROUND

Multiple myeloma (MM) is a clonal plasma cell disorder which still lacks sufficient prognostic factors. The serine/arginine-rich splicing factor (SRSF) family serves as an important splicing regulator in organ development. Among all members, SRSF1 plays an important role in cell proliferation and renewal. However, the role of SRSF1 in MM is still unknown.

METHODS

SRSF1 was selected from the primary bioinformatics analysis of SRSF family members, and then we integrated 11 independent datasets and analyzed the relationship between SRSF1 expression and MM clinical characteristics. Gene set enrichment analysis (GSEA) was conducted to explore the potential mechanism of SRSF1 in MM progression. ImmuCellAI was used to estimate the abundance of immune infiltrating cells between the SRSF1 and SRSF1 groups. The ESTIMATE algorithm was used to evaluate the tumor microenvironment in MM. The expression of immune-related genes was compared between the groups. Additionally, SRSF1 expression was validated in clinical samples. SRSF1 knockdown was conducted to explore the role of SRSF1 in MM development.

RESULTS

SRSF1 expression showed an increasing trend with the progression of myeloma. Besides, SRSF1 expression increased as the age, ISS stage, 1q21 amplification level, and relapse times increased. MM patients with higher SRSF1 expression had worse clinical features and poorer outcomes. Univariate and multivariate analysis indicated that upregulated SRSF1 expression was an independent poor prognostic factor for MM. Enrichment pathway analysis confirmed that SRSF1 takes part in the myeloma progression via tumor-associated and immune-related pathways. Several checkpoints and immune-activating genes were significantly downregulated in the SRSF1 groups. Furthermore, we detected that SRSF1 expression was significantly higher in MM patients than that in control donors. SRSF1 knockdown resulted in proliferation arrest in MM cell lines.

CONCLUSION

The expression value of SRSF1 is positively associated with myeloma progression, and high SRSF1 expression might be a poor prognostic biomarker in MM patients.

摘要

背景

多发性骨髓瘤（MM）是一种克隆性浆细胞疾病，目前仍缺乏足够的预后因素。富含丝氨酸/精氨酸的剪接因子（SRSF）家族在器官发育中作为重要的剪接调节因子。在所有成员中，SRSF1在细胞增殖和更新中起重要作用。然而，SRSF1在MM中的作用仍不清楚。

方法

从SRSF家族成员的初步生物信息学分析中选择SRSF1，然后整合11个独立数据集，分析SRSF1表达与MM临床特征之间的关系。进行基因集富集分析（GSEA）以探索SRSF1在MM进展中的潜在机制。使用ImmuCellAI估计SRSF1高表达组和低表达组之间免疫浸润细胞的丰度。采用ESTIMATE算法评估MM中的肿瘤微环境。比较两组之间免疫相关基因的表达。此外，在临床样本中验证SRSF1表达。进行SRSF1敲低以探索SRSF1在MM发展中的作用。

结果

SRSF1表达随骨髓瘤进展呈上升趋势。此外，SRSF1表达随着年龄、国际分期系统（ISS）分期、1q21扩增水平和复发次数的增加而增加。SRSF1表达较高的MM患者具有更差的临床特征和更差的预后。单因素和多因素分析表明，SRSF1表达上调是MM的独立不良预后因素。富集通路分析证实，SRSF1通过肿瘤相关和免疫相关通路参与骨髓瘤进展。在SRSF1高表达组中，几个检查点和免疫激活基因显著下调。此外，我们检测到MM患者中SRSF1表达明显高于对照供体。SRSF1敲低导致MM细胞系增殖停滞。