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IF 1 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Protein and Peptide Letters Pub Date : 2025-01-24 DOI:10.2174/0109298665351592250106062250

Guizhen Lyu, Dongbing Li

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引用次数: 0

摘要

背景：ZNF165在少数肿瘤中的作用仅有报道。ZNF165在肝癌、胃癌和乳腺癌中发挥着重要作用，尤其是在调节免疫微环境、促进肿瘤细胞增殖和迁移以及作为免疫治疗的潜在靶点方面：本研究旨在加深对 ZNF165 基因如何发挥作用并影响癌症发展的了解：我们利用一整套在线资源，包括 TIMER、TCGA、GTEx、GEPIA2、cBioPortal、TIMER2、STRING、DAVID、RNAactDrug、CancerSEA 和 UCSC，并结合综合统计分析，对 ZNF165 的泛癌症图谱进行了深入研究。这项研究包括对 ZNF165 水平、其与患者预后的关系以及临床相关性的评估。我们研究了 ZNF165 与微卫星不稳定性 (MSI)、肿瘤突变负荷 (TMB)、免疫细胞浸润和免疫检查点基因表达等关键癌症生物标志物之间的相互作用。我们深入研究了 ZNF165 的遗传变异、它在各种癌症类型中的生物学作用及其与药物反应性的潜在联系。我们分析了 ZNF165 的单细胞表达模式及其对癌症功能动态的影响。我们采用定量反转录 PCR（qRT-PCR）技术测量卵巢癌（OC）细胞系中的 ZNF165 水平：结果：ZNF165的表达在多种人类癌症中均出现异常，并与临床分期相关。ZNF165在KIRC、KIRP、STAD和UCEC中的高表达与总生存率低密切相关。ZNF165在特定肿瘤类型中具有令人鼓舞的诊断价值，基因扩增是主要的基因改变。我们的分析进一步发现，ZNF165 水平与三种不同癌症类型中的 MSI 以及六种不同恶性肿瘤中的 TMB 之间存在显著关联。我们发现 ZNF165 水平与免疫细胞浸润以及免疫检查点基因的表达之间存在很大的相关性。研究发现，ZNF165 参与了多种癌症类型的几种普遍信号通路。ZNF165可能会导致化疗和化疗耐药性，并被观察到参与癌症进展。为 OC 构建了一个涉及 AFDN-DT、miR-191-5p 和 ZNF165 的 ceRNA 调控网络，发现在 OC 细胞系中 ZNF165 水平显著升高。ZNF165在各种恶性肿瘤中的表达失调可能通过多种生物学途径在癌症的发生和发展中发挥作用：结论：ZNF165 可能是治疗人类癌症的一个很有前景的治疗靶点。

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ZNF165: A Pan-Cancer Biomarker with Prognostic and Therapeutic Potential.

Background: The role of ZNF165 in only a few tumors has been reported. ZNF165 plays an important role in liver cancer, gastric cancer, and breast cancer, especially in regulating the immune microenvironment, promoting tumor cell proliferation and migration, and serving as a potential target for immunotherapy.

Objective: This study aimed to enhance an understanding of how the ZNF165 gene functions and influences cancer development.

Methods: Using a suite of online resources, including TIMER, TCGA, GTEx, GEPIA2, cBioPortal, TIMER2, STRING, DAVID, RNAactDrug, CancerSEA, and UCSC, along with comprehensive statistical analyses, we conducted a thorough investigation of the pan-cancer landscape of ZNF165. This study encompassed an assessment of ZNF165 levels, their associations with patient outcomes, and clinical correlates. We examined the interplay between ZNF165 and key cancer biomarkers, such as Microsatellite Instability (MSI), Tumor Mutational Burden (TMB), immune cell infiltration, and the expression of immune checkpoint genes. We delved into the genetic variations of ZNF165, its biological roles across various cancer types, and its potential links to drug responsiveness. We analyzed single-cell expression patterns of ZNF165 and their implications for the functional dynamics of cancer. We employed quantitative Reverse Transcription PCR (qRT-PCR) to measure ZNF165 levels in Ovarian Cancer (OC) cell lines.

Results: ZNF165 expression displayed aberrations across a diverse range of human cancers and exhibited correlations with clinical stages. High ZNF165 expression in KIRC, KIRP, STAD, and UCEC was significantly associated with poor overall survival. ZNF165 has encouraging diagnostic value in specific tumor types, with gene amplification identified as the predominant genetic alteration. Our analysis further uncovered significant associations between ZNF165 levels and MSI across three distinct cancer types, as well as with TMB in six different malignancies. We detected substantial correlations between ZNF165 levels and immune cell infiltration, as well as the expression of immune checkpoint genes. ZNF165 was found to be involved in several prevalent signaling pathways across various cancer types. ZNF165 may potentially contribute to chemotherapy and chemoresistance, and was observed to be involved in cancer progression. A ceRNA regulatory network involving AFDN-DT, miR-191-5p, and ZNF165 was constructed for OC, revealing significantly elevated ZNF165 levels in OC cell lines. Dysregulated ZNF165 expression across a spectrum of malignancies might play a role in cancer initiation and advancement via multiple biological pathways.

Conclusion: ZNF165 may serve as a promising therapeutic target for the treatment of cancer in human patients.

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来源期刊

Protein and Peptide Letters 生物-生化与分子生物学

CiteScore

2.90

自引率

0.00%

发文量

审稿时长

2 months

期刊介绍： Protein & Peptide Letters publishes letters, original research papers, mini-reviews and guest edited issues in all important aspects of protein and peptide research, including structural studies, advances in recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, and drug design. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallization and preliminary structure determination of biologically important proteins are considered only if they include significant new approaches or deal with proteins of immediate importance, and preliminary structure determinations of biologically important proteins. Purely theoretical/review papers should provide new insight into the principles of protein/peptide structure and function. Manuscripts describing computational work should include some experimental data to provide confirmation of the results of calculations. Protein & Peptide Letters focuses on: Structure Studies Advances in Recombinant Expression Drug Design Chemical Synthesis Function Pharmacology Enzymology Conformational Analysis Immunology Biotechnology Protein Engineering Protein Folding Sequencing Molecular Recognition Purification and Analysis