Yan Huaqing, Zhang Liqi, Xu Fan, Chen Tieding, Li Rubing
Department of Urology, Ningbo Medical Center Lihuili Hospital, Ningbo, 315000, Zhejiang, People's Republic of China.
Department of Reproductive Medicine, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, Zhejiang, People's Republic of China.
Discov Oncol. 2025 Jun 16;16(1):1119. doi: 10.1007/s12672-025-02974-6.
BACKGROUND: DCAF5 encodes a component of ubiquitin ligase complex, thereby influencing protein ubiquitination. Recent research underscored its potential to revert the malignant phenotype, as evidenced in vivo studies, while the scarcity of research about DCAF5 challenges for its development as a novel target for cancer treatment. METHODS: We conducted an immunohistochemical analysis to compare the expression levels of DCAF5 in renal clear cell carcinoma tissues with those in adjacent non-neoplastic tissues. Subsequently, we performed survival analyses to explore the correlation between DCAF5 expression and patient outcomes. Multiple public databases were used such as the UCSC Xena platform, The Cancer Genome Atlas, and the Genotype-Tissue Expression project. The raw data extracted from the UCSC Xena platform was subsequently processed utilizing online analytical tools to facilitate further in-depth examination. RESULTS: Our investigation has discovered a significant reduction in DCAF5 expression within renal clear cell carcinoma tissues when juxtaposed with adjacent non-cancerous tissues. Further experimental validation demonstrated that patients with higher pathology grades exhibited lower DCAF5 expression. In a broader oncological context, our comprehensive analysis across various cancer types revealed a heterogeneous expression pattern of DCAF5. Concurrently, an examination of publicly accessible databases has highlighted a notable correlation between DCAF5 expression and both immune scores and immune cell infiltration in a range of cancer types. It is noteworthy that DCAF5 's potential as an immunotherapy biomarker was recognized, distinguishing it from several established markers in this domain. Finally, our analysis of genetic alterations identified gene amplification as the predominant form of aberration affecting the DCAF5 gene. CONCLUSION: Our findings reveal that DCAF5 exhibits context-dependent dual roles across cancers and demonstrates superior predictive value over traditional biomarkers like TMB in immunotherapy. This highlights its potential as a dual-functional biomarker for prognosis and immunotherapy personalization, particularly in SMARCB1-deficient malignancies.
背景：DCAF5编码泛素连接酶复合物的一个组成部分，从而影响蛋白质泛素化。最近的研究强调了其逆转恶性表型的潜力，体内研究证明了这一点，而关于DCAF5的研究稀缺，这对其作为癌症治疗新靶点的开发构成了挑战。 方法：我们进行了免疫组织化学分析，以比较肾透明细胞癌组织与相邻非肿瘤组织中DCAF5的表达水平。随后，我们进行了生存分析，以探讨DCAF5表达与患者预后之间的相关性。使用了多个公共数据库，如UCSC Xena平台、癌症基因组图谱和基因型-组织表达项目。从UCSC Xena平台提取的原始数据随后利用在线分析工具进行处理，以便于进一步深入研究。 结果：我们的研究发现，与相邻的非癌组织相比，肾透明细胞癌组织中DCAF5表达显著降低。进一步的实验验证表明，病理分级较高的患者DCAF5表达较低。在更广泛的肿瘤学背景下，我们对各种癌症类型的综合分析揭示了DCAF5的异质表达模式。同时，对公开可用数据库的检查突出了DCAF5表达与一系列癌症类型的免疫评分和免疫细胞浸润之间的显著相关性。值得注意的是，DCAF5作为免疫治疗生物标志物的潜力得到了认可，使其与该领域的几个既定标志物区分开来。最后，我们对基因改变的分析确定基因扩增是影响DCAF5基因的主要畸变形式。 结论：我们的研究结果表明，DCAF5在癌症中表现出依赖于背景的双重作用，并且在免疫治疗中比TMB等传统生物标志物具有更高的预测价值。这突出了其作为预后和免疫治疗个性化的双功能生物标志物的潜力，特别是在SMARCB1缺陷的恶性肿瘤中。
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