Prognostic and Immunologic Significance of SH2B2 in Colon Adenocarcinoma and its Relationship to Proliferation, Migration, and Invasion.

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS Combinatorial chemistry & high throughput screening Pub Date : 2024-12-18 DOI:10.2174/0113862073346075241118092413

Nan Bai, Minyan Liu, Qinghuai Li

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Abstract

Background: SH2B adaptor protein 2 (SH2B2, also named APS) is an adaptor protein implicated in the modulation of insulin signaling pathways and glucose metabolism. Its role in colon adenocarcinoma (COAD) is unknown.

Methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus database were utilized to assess SH2B2 expression and its clinical significance in COAD. We investigated the associations between SH2B2 expression with genomic instability, tumor mutational burden (TMB), DNA methylation, alternative splicing, immune infiltration, and drug sensitivity. A SH2B2 knockdown model was developed to examine its impact on COAD cellular functions.

Results: Highly expressed SH2B2 is associated with a poorer prognosis in COAD. SH2B2 expression in COAD is associated with copy number variations, microsatellite instability, methylation patterns, and alternative 5' splicing events, but not with TMB. SH2B2 is positively correlated with mostly immune cells and the expression of PD-1 and CTLA4. The IC50 values of ten drugs were significantly correlated with SH2B2 expression. BI-2536_1086 had a strong binding affinity with SH2B2. Furthermore, the knockdown of SH2B2 reduced the proliferation, migration, and invasion of COAD cells.

Conclusion: SH2B2 appears to act as an oncogene in COAD and may serve as a pivotal prognostic and therapeutic target, deserving further exploration.

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SH2B2在结肠腺癌中的预后和免疫学意义及其与增殖、迁移和侵袭的关系

背景：SH2B适配蛋白2 （SH2B2，也称为APS）是一种参与胰岛素信号通路和葡萄糖代谢调节的适配蛋白。它在结肠腺癌（COAD）中的作用尚不清楚。方法：利用Cancer Genome Atlas和Gene Expression Omnibus数据库的数据，评估SH2B2在COAD中的表达及其临床意义。我们研究了SH2B2表达与基因组不稳定性、肿瘤突变负担（TMB）、DNA甲基化、选择性剪接、免疫浸润和药物敏感性之间的关系。我们建立了一个SH2B2敲低模型来研究它对COAD细胞功能的影响。结果：高表达SH2B2与COAD患者预后较差相关。COAD中的SH2B2表达与拷贝数变化、微卫星不稳定性、甲基化模式和5'剪接事件相关，但与TMB无关。SH2B2与大部分免疫细胞及PD-1、CTLA4的表达呈正相关。10种药物的IC50值与SH2B2表达显著相关。BI-2536_1086与SH2B2具有较强的结合亲和力。此外，敲低SH2B2可降低COAD细胞的增殖、迁移和侵袭。结论：SH2B2在COAD中可能是一个癌基因，可能是一个关键的预后和治疗靶点，值得进一步探索。

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.