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Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma

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 prolifer...

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Autores principales: Zhang, Jiawei, Wang, Zanzan, Wang, Kailai, Xin, Dijia, Wang, Luyao, Fan, Yili, Xu, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191755/
https://www.ncbi.nlm.nih.gov/pubmed/37206090
http://dx.doi.org/10.1155/2023/9998927
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author Zhang, Jiawei
Wang, Zanzan
Wang, Kailai
Xin, Dijia
Wang, Luyao
Fan, Yili
Xu, Yang
author_facet Zhang, Jiawei
Wang, Zanzan
Wang, Kailai
Xin, Dijia
Wang, Luyao
Fan, Yili
Xu, Yang
author_sort Zhang, Jiawei
collection PubMed
description 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(high) and SRSF1(low) 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(high) 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.
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spelling pubmed-101917552023-05-18 Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma Zhang, Jiawei Wang, Zanzan Wang, Kailai Xin, Dijia Wang, Luyao Fan, Yili Xu, Yang J Oncol Research Article 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(high) and SRSF1(low) 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(high) 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. Hindawi 2023-05-10 /pmc/articles/PMC10191755/ /pubmed/37206090 http://dx.doi.org/10.1155/2023/9998927 Text en Copyright © 2023 Jiawei Zhang et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Jiawei
Wang, Zanzan
Wang, Kailai
Xin, Dijia
Wang, Luyao
Fan, Yili
Xu, Yang
Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma
title Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma
title_full Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma
title_fullStr Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma
title_full_unstemmed Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma
title_short Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma
title_sort increased expression of srsf1 predicts poor prognosis in multiple myeloma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10191755/
https://www.ncbi.nlm.nih.gov/pubmed/37206090
http://dx.doi.org/10.1155/2023/9998927
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