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透明细胞肾细胞癌中预后标志物及过氧化物酶体相关关键基因的鉴定与实验验证

Identification and Experimental Validation of Prognostic Signature and Peroxisome-Related Key Genes in Clear Cell Renal Cell Carcinoma.

作者信息

Fan Congcong, Li Yifei, Zhang Weizhi, Wang Yining, Li Yanzhen, Zheng Jianjian, Yu Zhixian, Guo Yong

机构信息

Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.

Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People's Republic of China.

出版信息

Int J Gen Med. 2025 May 23;18:2687-2702. doi: 10.2147/IJGM.S513102. eCollection 2025.

Abstract

INTRODUCTION

Clear cell renal cell carcinoma (ccRCC) is a common urological malignant tumor. Dysregulated peroxisomes contribute to the progression of cancers. However, the prognostic significance of peroxisome-related genes (PGs) in ccRCC is still poorly understood.

METHODS

PGs were collected from MsigDB. Prognostic differentially expressed genes were filtered via differentially expression analysis and univariate Cox regression analysis. The construction of risk model was performed by the least absolute shrinkage selection operator Cox regression analysis. Subsequently, the clinical application of risk model in prognosis prediction, tumor microenvironment (TME) and drug sensitivity was comprehensively evaluated. The expression levels of genes were measured by qRT-PCR and immunohistochemistry. Finally, the role of the genes of this risk model in biological behaviors of RCC cells was further verified via CCK-8, transwell invasion and wound healing assay.

RESULTS

A risk model, including 9 PGs, was established. The risk model exhibited a robust and accurate performance in prognostic prediction across TCGA, GSE167573 and the local cohorts. Moreover, the risk model was closely correlated with clinical characteristics, TME and drug sensitivity. Silencing of the key genes attenuated the proliferation, migration, and invasion ability of RCC cells.

CONCLUSION

The novel peroxisome-related risk model holds promise as a prognostic tool for estimating the prognosis of ccRCC patients and provides insights into treatment strategies.

摘要

引言

透明细胞肾细胞癌(ccRCC)是一种常见的泌尿系统恶性肿瘤。过氧化物酶体失调会促进癌症进展。然而,过氧化物酶体相关基因(PGs)在ccRCC中的预后意义仍知之甚少。

方法

从MsigDB中收集PGs。通过差异表达分析和单变量Cox回归分析筛选预后差异表达基因。采用最小绝对收缩选择算子Cox回归分析构建风险模型。随后,全面评估风险模型在预后预测、肿瘤微环境(TME)和药物敏感性方面的临床应用。通过qRT-PCR和免疫组织化学检测基因表达水平。最后,通过CCK-8、Transwell侵袭和伤口愈合试验进一步验证该风险模型的基因在肾癌细胞生物学行为中的作用。

结果

建立了一个包含9个PGs的风险模型。该风险模型在TCGA、GSE167573和本地队列的预后预测中表现出强大而准确的性能。此外,风险模型与临床特征、TME和药物敏感性密切相关。关键基因的沉默减弱了肾癌细胞的增殖、迁移和侵袭能力。

结论

新的过氧化物酶体相关风险模型有望作为评估ccRCC患者预后的预后工具,并为治疗策略提供见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/73c9/12109615/e689f86ff016/IJGM-18-2687-g0001.jpg

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