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细胞分裂周期20促进肿瘤进展,并预示儿童和成人肾上腺皮质癌的临床预后不良。

Cell division cycle 20 promotes tumor progression and predicts poor clinical outcome in childhood and adult adrenocortical carcinoma.

作者信息

Chen Jiahong, Huang Peisheng, Shi Yongcheng, Mo Shanshan, Hsu Cheng-Ya, Fang Shumin, Zhong Chuanfan, Zhang Le, Zuo Lanting, Lu Jianming, Zhong Weide, Huang Zhuoya, Dong Zhong

机构信息

Department of Urology, Huizhou Central People's Hospital, Huizhou 516001 Guangdong, China.

The First Clinical Medical College, Guangdong Medical University, Zhanjiang 524023 Guangdong, China.

出版信息

J Clin Transl Endocrinol. 2025 Jul 2;41:100406. doi: 10.1016/j.jcte.2025.100406. eCollection 2025 Sep.

Abstract

BACKGROUND

Adrenocortical carcinoma (ACC) is an uncommon and highly aggressive tumor with a grim prognosis. Numerous investigations have elucidated a close association between the dysregulated expression of multiple genes within tumors and the initiation as well as progression of neoplasms. These dysregulated genes not only exert pivotal roles in tumorigenesis but also harbor significant potential as prognostic biomarkers.

METHODS

This study utilized transcriptomic data from public databases of ACC and normal tissue samples to screen for differentially expressed genes (DEGs). Subsequently, univariate Cox regression and receiver operating characteristic (ROC) curve were employed to identify potential prognostic biomarkers for ACC. Immunohistochemistry and in vitro cell experiments were conducted to validate the expression and potential functions of Cell division cycle 20 (CDC20) in ACC cells. Additionally, we analyzed the relationship between CDC20 and CD8+ T cells, immunotherapy response, somatic mutations, and copy number variations.

RESULTS

CDC20 has emerged as an independent adverse prognostic factor in ACC, with significantly elevated expression levels. In vitro cell experiments have demonstrated that downregulation of CDC20 expression suppresses proliferation and migration of ACC cells. Notably, our study has identified CDC20 expression as most closely associated with TP53 mutation. Additionally, CDC20 expression levels exhibit a negative correlation with infiltration of CD8+ T cells. Patients with low CDC20 expression may show improved response to anti-PD-1 immunotherapy.

CONCLUSION

CDC20 serves as a reliable and robust biomarker in ACC, playing a crucial role in predicting survival outcomes and assessing immunotherapy response in adult and childhood ACC patients.

摘要

背景

肾上腺皮质癌(ACC)是一种罕见且侵袭性很强的肿瘤,预后很差。大量研究阐明了肿瘤内多个基因的表达失调与肿瘤的发生及进展密切相关。这些失调的基因不仅在肿瘤发生中起关键作用,而且作为预后生物标志物具有巨大潜力。

方法

本研究利用ACC和正常组织样本公共数据库中的转录组数据筛选差异表达基因(DEG)。随后,采用单变量Cox回归和受试者工作特征(ROC)曲线来识别ACC的潜在预后生物标志物。进行免疫组织化学和体外细胞实验以验证细胞分裂周期20(CDC20)在ACC细胞中的表达及潜在功能。此外,我们分析了CDC20与CD8 + T细胞、免疫治疗反应、体细胞突变及拷贝数变异之间的关系。

结果

CDC20已成为ACC中一个独立的不良预后因素,其表达水平显著升高。体外细胞实验表明,下调CDC20表达可抑制ACC细胞的增殖和迁移。值得注意的是,我们的研究发现CDC20表达与TP53突变关系最为密切。此外,CDC20表达水平与CD8 + T细胞浸润呈负相关。CDC20表达低的患者对抗PD - 1免疫治疗可能有更好的反应。

结论

CDC20是ACC中一种可靠且强大的生物标志物,在预测成人和儿童ACC患者的生存结果及评估免疫治疗反应方面发挥着关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5088/12272758/46f0acbe7943/gr1.jpg

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