探讨细胞周期相关基因 CHMP4C 在前列腺癌中的临床和生物学意义。
Exploring the clinical and biological significance of the cell cycle-related gene CHMP4C in prostate cancer.
机构信息
Department of Urology, Lanzhou University Second Hospital, Lanzhou, 730030, China.
Department of plastic surgery, Lanzhou University Second Hospital, Lanzhou, 730030, China.
出版信息
BMC Med Genomics. 2024 Aug 13;17(1):210. doi: 10.1186/s12920-024-01970-z.
BACKGROUND
Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease's evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear.
METHODS
In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells.
RESULTS
The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency.
CONCLUSIONS
Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.
背景
前列腺癌（PCa）是影响男性健康的第二大常见恶性肿瘤，在患者治疗和预后管理方面，该疾病的进化过程极具挑战性。多泡体蛋白 4C（CHMP4C）通过调节细胞周期功能参与多种癌症的发生。然而，CHMP4C 在前列腺癌中的作用尚不清楚。
方法
在生物信息学方面，使用多个 PCa 数据集研究 CHMP4C 的表达情况。通过生存分析和列线图方法探讨 CHMP4C 的预后意义。进行基因集富集分析（GSEA）以探究 CHMP4C 的功能意义。在细胞实验方面，通过 qRT-PCR 和 Western blot 检测 RNA 和蛋白表达水平的验证。在建立稳定敲低 CHMP4C 的细胞系后，进行一系列实验，包括细胞计数试剂盒-8（CCK-8）、划痕愈合、Transwell 和流式细胞术，以探究 CHMP4C 对 PCa 细胞增殖、迁移、侵袭和细胞周期功能的影响。
结果
CHMP4C 在 PCa 细胞和组织中均呈上调表达，且表达水平升高的患者预后明显较差。使用 CHMP4C 结合临床病理特征构建的列线图表现出出色的预后预测能力。CHMP4C 敲低显著抑制 PCa 细胞（LNcaP 和 PC3）的增殖、迁移和侵袭。CHMP4C 可影响 PCa 细胞周期的进展，其表达可能受小檗碱调节。PCa 患者中 CHMP4C 的不同表达可能导致免疫细胞浸润和基因突变频率的改变。
结论
我们的研究结果表明，CHMP4C 可能是 PCa 的预后生物标志物，为 PCa 的精准治疗提供了新的视角。
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