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鉴定和验证三个与去势抵抗性前列腺癌细胞增殖和预后相关的枢纽基因。

Identification and Validation of Three Hub Genes Involved in Cell Proliferation and Prognosis of Castration-Resistant Prostate Cancer.

机构信息

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

出版信息

Oxid Med Cell Longev. 2022 Aug 17;2022:8761112. doi: 10.1155/2022/8761112. eCollection 2022.

DOI:10.1155/2022/8761112
PMID:36035209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9402298/
Abstract

BACKGROUND

The acquisition of castration resistance is lethal and inevitable in most prostate cancer patients under hormone therapy. However, effective biomarkers and therapeutic targets for castration-resistant prostate cancer remain to be defined.

METHODS

Comprehensive bioinformatics tools were used to screen hub genes in castration-resistant prostate cancer and were verified in androgen-dependent prostate cancer and castration-resistant prostate cancer in TCGA and the SU2C/PCF Dream Team database, respectively. Gene set enrichment analysis and in vitro experiments were performed to determine the potential functions of hub genes involved in castration-resistant prostate cancer progression.

RESULTS

Three hub genes were screened out by bioinformatics analysis: MCM4, CENPI, and KNTC1. These hub genes were upregulated in castration-resistant prostate cancer and showed high diagnostic and prognostic value. Moreover, the expression levels of the hub genes were positively correlated with neuroendocrine prostate cancer scores, which represent the degree of castration-resistant prostate cancer aggression. Meanwhile, in vitro experiments confirmed that hub gene expression was increased in castration-resistant prostate cancer cell lines and that inhibition of hub genes hindered cell cycle transition, resulting in suppression of castration-resistant prostate cancer cell proliferation, which confirmed the gene set enrichment analysis results.

CONCLUSIONS

MCM4, CENPI, and KNTC1 could serve as candidate diagnostic and prognostic biomarkers of castration-resistant prostate cancer and may provide potential preventive and therapeutic targets.

摘要

背景

在大多数接受激素治疗的前列腺癌患者中，获得去势抵抗是致命且不可避免的。然而，去势抵抗性前列腺癌的有效生物标志物和治疗靶点仍有待确定。

方法

综合生物信息学工具筛选去势抵抗性前列腺癌的枢纽基因，并分别在 TCGA 和 SU2C/PCF Dream Team 数据库中的雄激素依赖性前列腺癌和去势抵抗性前列腺癌中进行验证。进行基因集富集分析和体外实验，以确定参与去势抵抗性前列腺癌进展的枢纽基因的潜在功能。

结果

通过生物信息学分析筛选出三个枢纽基因：MCM4、CENPI 和 KNTC1。这些枢纽基因在去势抵抗性前列腺癌中上调，具有较高的诊断和预后价值。此外，枢纽基因的表达水平与神经内分泌前列腺癌评分呈正相关，代表去势抵抗性前列腺癌侵袭的程度。同时，体外实验证实，去势抵抗性前列腺癌细胞系中枢纽基因表达增加，抑制枢纽基因阻碍细胞周期转换，从而抑制去势抵抗性前列腺癌细胞增殖，这证实了基因集富集分析的结果。

结论

MCM4、CENPI 和 KNTC1 可作为去势抵抗性前列腺癌的候选诊断和预后生物标志物，并可能为预防和治疗提供潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/46a2d1daa3a9/OMCL2022-8761112.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/1685096d67a8/OMCL2022-8761112.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/dc78fe8e5527/OMCL2022-8761112.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/b3088cd7fd0f/OMCL2022-8761112.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/927f323dc6ac/OMCL2022-8761112.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/db3f7304b4e4/OMCL2022-8761112.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/899492db2837/OMCL2022-8761112.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/e94cf23b8a32/OMCL2022-8761112.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/46a2d1daa3a9/OMCL2022-8761112.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/1685096d67a8/OMCL2022-8761112.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/dc78fe8e5527/OMCL2022-8761112.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/b3088cd7fd0f/OMCL2022-8761112.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/927f323dc6ac/OMCL2022-8761112.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/db3f7304b4e4/OMCL2022-8761112.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/899492db2837/OMCL2022-8761112.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/e94cf23b8a32/OMCL2022-8761112.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/790a/9402298/46a2d1daa3a9/OMCL2022-8761112.008.jpg

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