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全面的泛癌分析显示,CDC6是一种潜在的免疫调节因子,也是胰腺癌中有前景的治疗靶点。

Comprehensive pan-cancer analysis reveals CDC6 as a potential immunomodulatory agent and promising therapeutic target in pancreatic cancer.

作者信息

Pu Dongyao, Xu Yingkun, Yu Haochen, Yang Ting, Tang Lingfeng, Tan Wenhao, Zhang Wenjie, Liu Shengchun

机构信息

Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.

出版信息

Transl Cancer Res. 2024 Aug 31;13(8):4096-4112. doi: 10.21037/tcr-24-505. Epub 2024 Aug 23.

Abstract

BACKGROUND

CDC6 is critical in DNA replication initiation, but its expression patterns and clinical implications in cancer are underexplored. This study uses multi-omics data from The Cancer Genome Atlas (TCGA) to comprehensively analyze CDC6 across various cancers, aiming to evaluate its potential as a prognostic biomarker and explore its role in immunotherapy.

METHODS

By leveraging multi-omics data from TCGA, we conducted a comprehensive analysis of CDC6 expression across a variety of cancer types. Least absolute shrinkage and selection operator (LASSO) regression was employed to assess the association of CDC6 with key molecules implicated in pancreatic cancer.

RESULTS

CDC6 expression was found to be significantly upregulated across a broad spectrum of cancers. High levels of CDC6 expression were associated with poor prognosis in several cancer types. Notable associations were observed between CDC6 expression and tumor mutational burden (TMB), microsatellite instability (MSI), as well as immune cell infiltration. Co-expression analysis revealed significant associations between CDC6 and prevalent immune checkpoint genes. A risk model incorporating CDC6-related genes, including CCNA1, CCNA2, CCND1, CCND2, CDC25B, CDC6, and CDK2, was developed for pancreatic cancer.

CONCLUSIONS

CDC6 emerges as a promising prognostic biomarker and a potential target for immunotherapy across various cancers, including pancreatic cancer. It appears to modulate immune responses across cancer types, highlighting its regulatory role. Further exploration into the biological functions and clinical implications of CDC6 is warranted.

摘要

背景

细胞分裂周期蛋白6(CDC6)在DNA复制起始过程中至关重要,但其在癌症中的表达模式及临床意义尚未得到充分研究。本研究利用来自癌症基因组图谱(TCGA)的多组学数据,全面分析了CDC6在各种癌症中的情况,旨在评估其作为预后生物标志物的潜力,并探索其在免疫治疗中的作用。

方法

通过利用TCGA的多组学数据,我们对多种癌症类型中CDC6的表达进行了全面分析。采用最小绝对收缩和选择算子(LASSO)回归来评估CDC6与胰腺癌相关关键分子的关联。

结果

发现CDC6在广泛的癌症中表达显著上调。在几种癌症类型中,高水平的CDC6表达与预后不良相关。观察到CDC6表达与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)以及免疫细胞浸润之间存在显著关联。共表达分析揭示了CDC6与常见免疫检查点基因之间存在显著关联。为胰腺癌建立了一个包含与CDC6相关基因的风险模型,这些基因包括CCNA1、CCNA2、CCND1、CCND2、CDC25B、CDC6和CDK2。

结论

CDC6成为一种有前景的预后生物标志物,也是包括胰腺癌在内的各种癌症免疫治疗的潜在靶点。它似乎在不同癌症类型中调节免疫反应,凸显了其调节作用。有必要进一步探索CDC6的生物学功能和临床意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/606a/11384319/143b3150a794/tcr-13-08-4096-f1.jpg

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