Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer

BackgroundProstate cancer is the most common tumor in men worldwide, seriously threatening the health of older men, and 5-methylcytosine (m5C) RNA modification has been shown to have a significant impact on the development and progression of various tumors. However, as the most critical methyltransf...

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Main Authors: Guangyu Sun, Shenfei Ma, Zhiwen Zheng, Xiaohua Wang, Shuaiqi Chen, Taihao Chang, Zhengxin Liang, Yuchen Jiang, Shengxian Xu, Ranlu Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2022.965571/full
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author Guangyu Sun
Shenfei Ma
Zhiwen Zheng
Xiaohua Wang
Shuaiqi Chen
Taihao Chang
Zhengxin Liang
Yuchen Jiang
Shengxian Xu
Ranlu Liu
author_facet Guangyu Sun
Shenfei Ma
Zhiwen Zheng
Xiaohua Wang
Shuaiqi Chen
Taihao Chang
Zhengxin Liang
Yuchen Jiang
Shengxian Xu
Ranlu Liu
author_sort Guangyu Sun
collection DOAJ
description BackgroundProstate cancer is the most common tumor in men worldwide, seriously threatening the health of older men, and 5-methylcytosine (m5C) RNA modification has been shown to have a significant impact on the development and progression of various tumors. However, as the most critical methyltransferase for m5c RNA modification, the role of the NSUN members (NSUN1-7) in prostate cancer is unclear.MethodsWe obtained sequencing data of genes and related clinical data of prostate cancer from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database and analyzed the correlation between NSUN members’ expression and prognosis. we found that NSUN2 was closely implicated in the prognosis of prostate cancer, then verified the expression of NSUN2 in clinical samples, and obtained the correlation between NSUN2 and immune cell infiltration through CIBERSORT algorithm and ESTIMATE method. The relationship between NSUN2 copy number variation and immune cell infiltration was further analyzed in the TIMER database and identified signaling pathways associated with NSUN2 expression by GO, KEGG, and GSEA analysis. Finally, we verified the expression of NSUN2 in prostate cancer cell lines and confirmed the role of NSUN2 on the biological behavior of prostate cancer cells by proliferation and migration-related assays.ResultsNOP2 and NSUN2 were upregulated in prostate tumor tissues. NSUN2 expression is closely associated with tumor prognosis. NSUN2 high expression implies poor clinical features, and the NSUN family is significantly associated with tumor stromal score and immune score. Besides, NSUN2 is associated with a variety of immune infiltrating cells (B cells memory, T cells CD4 memory resting, T cells CD4 memory activated, NK cells resting, and so on). High NSUN2 expression lowers the sensitivity of many chemotherapy drugs, such as docetaxel, doxorubicin, fluorouracil, cisplatin, and etoposide. In prostate cancer, the most common type of mutation in NSUN2 is amplification, and NSUN2 copy number variation is closely associated with NSUN2 expression and immune cell infiltration. GSEA analysis showed that the related genes were mainly enriched in ubiquitin-mediated protein hydrolysis, cell cycle, RNA degradation, endometrial cancer, prostate cancer, p53 signaling pathway, and NSUN2 potentiated the proliferation and migration of prostate cancer cells.ConclusionsNSUN2 is highly expressed in prostate cancer, which contributes to the progression of prostate cancer, and is closely implicated in immune cell infiltration and chemotherapy drugs. NSUN2 is expected to be a prospective marker and a new treatment target for prostate cancer.
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spelling doaj.art-27feae422be34cf28304a7eeff8ca7482022-12-22T01:33:28ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-08-011210.3389/fonc.2022.965571965571Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancerGuangyu SunShenfei MaZhiwen ZhengXiaohua WangShuaiqi ChenTaihao ChangZhengxin LiangYuchen JiangShengxian XuRanlu LiuBackgroundProstate cancer is the most common tumor in men worldwide, seriously threatening the health of older men, and 5-methylcytosine (m5C) RNA modification has been shown to have a significant impact on the development and progression of various tumors. However, as the most critical methyltransferase for m5c RNA modification, the role of the NSUN members (NSUN1-7) in prostate cancer is unclear.MethodsWe obtained sequencing data of genes and related clinical data of prostate cancer from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database and analyzed the correlation between NSUN members’ expression and prognosis. we found that NSUN2 was closely implicated in the prognosis of prostate cancer, then verified the expression of NSUN2 in clinical samples, and obtained the correlation between NSUN2 and immune cell infiltration through CIBERSORT algorithm and ESTIMATE method. The relationship between NSUN2 copy number variation and immune cell infiltration was further analyzed in the TIMER database and identified signaling pathways associated with NSUN2 expression by GO, KEGG, and GSEA analysis. Finally, we verified the expression of NSUN2 in prostate cancer cell lines and confirmed the role of NSUN2 on the biological behavior of prostate cancer cells by proliferation and migration-related assays.ResultsNOP2 and NSUN2 were upregulated in prostate tumor tissues. NSUN2 expression is closely associated with tumor prognosis. NSUN2 high expression implies poor clinical features, and the NSUN family is significantly associated with tumor stromal score and immune score. Besides, NSUN2 is associated with a variety of immune infiltrating cells (B cells memory, T cells CD4 memory resting, T cells CD4 memory activated, NK cells resting, and so on). High NSUN2 expression lowers the sensitivity of many chemotherapy drugs, such as docetaxel, doxorubicin, fluorouracil, cisplatin, and etoposide. In prostate cancer, the most common type of mutation in NSUN2 is amplification, and NSUN2 copy number variation is closely associated with NSUN2 expression and immune cell infiltration. GSEA analysis showed that the related genes were mainly enriched in ubiquitin-mediated protein hydrolysis, cell cycle, RNA degradation, endometrial cancer, prostate cancer, p53 signaling pathway, and NSUN2 potentiated the proliferation and migration of prostate cancer cells.ConclusionsNSUN2 is highly expressed in prostate cancer, which contributes to the progression of prostate cancer, and is closely implicated in immune cell infiltration and chemotherapy drugs. NSUN2 is expected to be a prospective marker and a new treatment target for prostate cancer.https://www.frontiersin.org/articles/10.3389/fonc.2022.965571/fullprostate cancerimmune cell infiltrationmutationNSun25-Methylcytosine (5mC)
spellingShingle Guangyu Sun
Shenfei Ma
Zhiwen Zheng
Xiaohua Wang
Shuaiqi Chen
Taihao Chang
Zhengxin Liang
Yuchen Jiang
Shengxian Xu
Ranlu Liu
Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
Frontiers in Oncology
prostate cancer
immune cell infiltration
mutation
NSun2
5-Methylcytosine (5mC)
title Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
title_full Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
title_fullStr Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
title_full_unstemmed Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
title_short Multi-omics analysis of expression and prognostic value of NSUN members in prostate cancer
title_sort multi omics analysis of expression and prognostic value of nsun members in prostate cancer
topic prostate cancer
immune cell infiltration
mutation
NSun2
5-Methylcytosine (5mC)
url https://www.frontiersin.org/articles/10.3389/fonc.2022.965571/full
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