SLC16A3 is a Prognostic Marker and Affects Immune Regulation in Bladder Cancer.

IF 1.6 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Chengjun Li, Guangdi Chu, Guofeng Ma, Xinlei Chen, Xiaocheng Ma, Haitao Niu
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引用次数: 0

Abstract

Background: Overexpression of SLC16A3 can contribute to the development of various tumors by regulating metabolism, but a systematic analysis of SLC16A3 in bladder cancer (BC) has been rarely reported.

Methods: We used the BC datasets from public databases to investigate SLC16A3 expression in BC. We first analysed the relationship between SLC16A3 expression and clinical characteristics of 412 bladder cancer patients. After that, gene function analyses and immunocorrelation analyses of SLC16A3 were conducted with the R package. For immunotherapy effect and drug sensitivity analysis, we also used the R package. We also analysed the relation between SLC16A3 expression and 20 m6A modification key genes. Finally, we determined the expression localization of SLC16A3 in bladder cancer by single-cell sequencing analysis using 3,115 BC cells. We further detected the expression of SLC16A3/MCT4 on BC samples by reversed transcriptionquantitative polymerase chain reaction and immunohistochemistry.

Results: The SLC16A3 was overexpressed in BC cells, including epithelial cells (p<0.001). The high SLC16A3 expression level of patients with BC was significantly related to poor prognosis (p=0.044), and we established a reliable prognosis model for BC patients. Statistically significant associations between SLC16A3 and m6A modification (ALKBH5) gene (p<0.001), key genes in aerobic glycolysis, M2 macrophage infiltration (p=0.0058), and immune checkpoint regulation were observed.

Conclusion: Overexpression of SLC16A3 is an independent prognostic factor in patients with BC. SLC16A3 may influence the immune infiltration of BC by regulating BC metabolism and m6A methylation, which ultimately can lead to the progress of BC. For the detection and therapy of BC, SLC16A3 may be a potent therapeutic target for BC.

SLC16A3 是膀胱癌的预后标志并影响免疫调节
背景:SLC16A3的过表达可通过调节新陈代谢导致多种肿瘤的发生,但系统分析SLC16A3在膀胱癌(BC)中的表达却鲜有报道:方法:我们利用公共数据库中的膀胱癌数据集研究 SLC16A3 在膀胱癌中的表达。我们首先分析了 412 例膀胱癌患者的 SLC16A3 表达与临床特征之间的关系。之后,我们使用 R 软件包对 SLC16A3 进行了基因功能分析和免疫相关性分析。在免疫治疗效果和药物敏感性分析方面,我们也使用了 R 软件包。我们还分析了 SLC16A3 表达与 20 个 m6A 修饰关键基因之间的关系。最后,我们利用 3,115 个 BC 细胞进行单细胞测序分析,确定了 SLC16A3 在膀胱癌中的表达定位。我们还通过反转录定量聚合酶链反应和免疫组化进一步检测了 SLC16A3/MCT4 在膀胱癌样本中的表达:结果:SLC16A3在包括上皮细胞在内的BC细胞中过表达(p<0.001)。SLC16A3的高表达水平与BC患者的不良预后显著相关(p=0.044),我们为BC患者建立了一个可靠的预后模型。SLC16A3与m6A修饰(ALKBH5)基因(p<0.001)、有氧糖酵解关键基因、M2巨噬细胞浸润(p=0.0058)和免疫检查点调控之间存在统计学意义的关联:结论:SLC16A3的过表达是BC患者的一个独立预后因素。结论:SLC16A3的过表达是BC患者的独立预后因素,SLC16A3可能通过调节BC代谢和m6A甲基化影响BC的免疫浸润,最终导致BC的进展。对于BC的检测和治疗,SLC16A3可能是BC的一个有效治疗靶点。
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来源期刊
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.
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