KLHL17 as a Prognostic Indicator and Therapeutic Target in Cervical Cancer: A Comprehensive Analysis.

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Combinatorial chemistry & high throughput screening Pub Date : 2025-05-13 DOI:10.2174/0113862073378446250417123724

Guizhen Lyu, Jinyuan Li, Dongbing Li

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引用次数: 0

Abstract

Background: The role of kelch like family member 17 (KLHL17) in cervical cancer (CESC) is unclear.

Objective: To clarify this uncertainty, our research employed bioinformatics analysis coupled with experimental corroboration.

Methods: We utilized the Cancer Genome Atlas (TCGA) database to assess the expression of KLHL17 in various cancers, specifically CESC, and to explore its association with clinical characteristics, diagnostic utility, and prognostic significance in CESC. The current investigation delved into the potential regulatory pathways related to KLHL17, examining its connection with the infiltration of immune cells, the expression of immune checkpoint genes, the status of microsatellite instability (MSI), and the efficacy of diverse therapeutic agents in CESC. The research analyzed KLHL17 expression patterns using single-cell sequencing data from CESC samples and investigated the genetic variations of KLHL17 within this context. KLHL17 expression was validated using GSE145372. The presence and levels of KLHL17 in different cell lines were validated through quantitative real-time PCR (qRT-PCR) assays.

Results: KLHL17 exhibited irregular expression profiles across various cancer types, including CESC. Furthermore, increased KLHL17 levels in CESC patients were significantly associated with a lower progression-free survival (PFS) rate (hazard ratio: 1.62; 95% confidence interval: 1.01-2.60, p = 0.044). Moreover, KLHL17 expression emerged as a distinct prognostic indicator for CESC patients (p = 0.031). It has been associated with various biological pathways, such as cytokine-cytokine receptor interaction, primary immunodeficiency, cell adhesion molecules (CAMs), chemokine signaling pathway, steroid hormone biosynthesis, and others. The expression levels of KLHL17 were found to correlate with the presence of immune cells, the expression of immune checkpoint genes, and the status of MSI within CESC. Furthermore, KLHL17 expression exhibited a significant and inverse correlation with XMD15-27, rTRAIL, Paclitaxel, tp4ek, and tp4ek-k6. Furthermore, KLHL17 was found to be significantly positively regulated in CESC cell lines.

Conclusion: KLHL17 is a promising prognostic marker and potential therapeutic target in CESC.

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KLHL17作为宫颈癌预后指标和治疗靶点的综合分析。

背景：kelch样家族成员17 （KLHL17）在宫颈癌（CESC）中的作用尚不清楚。目的：为了澄清这种不确定性，我们的研究采用了生物信息学分析和实验验证相结合的方法。方法：利用癌症基因组图谱（TCGA）数据库评估KLHL17在各种癌症，特别是CESC中的表达，并探讨其与CESC临床特征、诊断价值和预后的关系。目前的研究深入研究了与KLHL17相关的潜在调控途径，研究了其与免疫细胞浸润、免疫检查点基因表达、微卫星不稳定性（MSI）状态以及多种治疗药物在CESC中的疗效的关系。该研究利用来自CESC样本的单细胞测序数据分析了KLHL17的表达模式，并在此背景下研究了KLHL17的遗传变异。使用GSE145372验证KLHL17表达。通过实时荧光定量PCR （qRT-PCR）检测KLHL17在不同细胞系中的存在和水平。结果：KLHL17在包括CESC在内的各种癌症类型中表现出不规则的表达谱。此外，CESC患者中KLHL17水平升高与较低的无进展生存率（PFS）显著相关(风险比：1.62；95%置信区间：1.01-2.60,p = 0.044)。此外，KLHL17表达成为CESC患者的一个明显的预后指标（p = 0.031）。它与多种生物学途径有关，如细胞因子-细胞因子受体相互作用、原发性免疫缺陷、细胞粘附分子（CAMs）、趋化因子信号通路、类固醇激素生物合成等。发现KLHL17的表达水平与免疫细胞的存在、免疫检查点基因的表达以及CESC内MSI的状态相关。此外，KLHL17的表达与XMD15-27、rTRAIL、Paclitaxel、tp4ek和tp4ek-k6呈显著负相关。此外，发现KLHL17在CESC细胞系中显著正调控。结论：KLHL17是CESC的预后标志物和潜在的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Combinatorial chemistry & high throughput screening 化学-生化研究方法

CiteScore

3.10

自引率

5.60%

发文量

327

审稿时长

7.5 months

期刊介绍： Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.