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泛癌中 ERCC 家族和膀胱癌中 ERCC2 的生物信息学分析。

Bioinformatics analysis of ERCC family in pan-cancer and ERCC2 in bladder cancer.

机构信息

Department of Urology, The affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China.

Postgraduate Training Base of Dalian Medical University, The affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, Jiangsu, China.

出版信息

Front Immunol. 2024 Aug 13;15:1402548. doi: 10.3389/fimmu.2024.1402548. eCollection 2024.

Abstract

BACKGROUND

Single nucleotide polymorphisms (SNPs) in DNA repair genes can impair protein function and hinder DNA repair, leading to genetic instability and increased cancer risk. The Excision Repair Cross-Complementation (ERCC) family plays a crucial role in nucleotide excision repair, yet their comprehensive multi-omics characterization and roles in tumor prognosis and immune microenvironment remain unexplored.

METHODS AND MATERIALS

We performed bioinformatics analysis using publicly available data from 33 cancer types to investigate associations between ERCC gene expression, patient prognosis, and clinical features. We also validated the role of ERCC2 in bladder cancer through assays, including CCK-8, colony formation, wound healing, and Transwell assays.

RESULTS

By utilizing the most recent database, we have conducted an analysis that reveals associations between variations in ERCC expression across multiple cancer types and both patient prognosis and the tumor microenvironment. To ensure the reliability of our findings, we applied the Benjamini-Hochberg procedure to adjust for multiple testing. After correction, we identified that ERCC expression levels remained significantly correlated with patient prognosis in various cancer types (p < 0.05). In addition, according to the results of drug sensitivity studies of anticancer drugs, there is a large correlation between ERCC expression and the sensitivity of different anticancer drugs. Finally, cell behavioral assays determined that knockdown of ERCC2 gene expression significantly inhibited the proliferation, migration and invasion of bladder cancer cells.

CONCLUSION

Through in-depth exploration of ERCC differential expression and its correlation with immune-related indicators, the unique microenvironment of tumors, and patient prognosis, we verified the potential role of ERCC2 in the process of bladder cancer genesis and progression. Therefore, we believe that the ERCC family of genes is expected to be a new option for cancer treatment and deserves to be further explored in the future.

摘要

背景

DNA 修复基因中的单核苷酸多态性(SNPs)会损害蛋白质功能并阻碍 DNA 修复,导致遗传不稳定性增加和癌症风险增加。切除修复交叉互补(ERCC)家族在核苷酸切除修复中发挥着关键作用,但它们在肿瘤预后和免疫微环境中的综合多组学特征和作用仍未被探索。

方法和材料

我们使用来自 33 种癌症类型的公共可用数据进行了生物信息学分析,以研究 ERCC 基因表达与患者预后和临床特征之间的关联。我们还通过 CCK-8、集落形成、划痕愈合和 Transwell assays 等实验验证了 ERCC2 在膀胱癌中的作用。

结果

通过利用最新的数据库,我们进行了一项分析,揭示了 ERCC 表达在多种癌症类型中的变化与患者预后和肿瘤微环境之间的关联。为了确保我们发现的可靠性,我们应用了 Benjamini-Hochberg 程序来调整多重检验。校正后,我们发现 ERCC 表达水平在各种癌症类型中与患者预后仍显著相关(p < 0.05)。此外,根据抗癌药物药物敏感性研究的结果,ERCC 表达与不同抗癌药物的敏感性之间存在很大的相关性。最后,细胞行为学测定表明,敲低 ERCC2 基因表达显著抑制了膀胱癌细胞的增殖、迁移和侵袭。

结论

通过深入探讨 ERCC 差异表达及其与免疫相关指标、肿瘤独特的微环境以及患者预后的相关性,我们验证了 ERCC2 在膀胱癌发生和进展过程中的潜在作用。因此,我们认为 ERCC 基因家族有望成为癌症治疗的新选择,值得在未来进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7692/11347307/7a2539088d8c/fimmu-15-1402548-g001.jpg

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