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研究OAS家族基因在乳腺癌中的临床意义:一项体外和计算机模拟研究。

Investigating the clinical significance of OAS family genes in breast cancer: an in vitro and in silico study.

作者信息

Lu Jinjun, Yang Lu, Yang Xinghai, Chen Bin, Liu Zheqi

机构信息

Department of General Surgery, Nantong Haimen People's Hospital, NanTong, JiangSu, 226100, China.

Department of Clinical Laboratory, Chongqing University Cancer Hospital, Chongqing, 400030, China.

出版信息

Hereditas. 2024 Dec 5;161(1):50. doi: 10.1186/s41065-024-00353-9.

Abstract

BACKGROUND

Breast cancer is the most common malignancy among women worldwide, characterized by complex molecular and cellular heterogeneity. Despite advances in diagnosis and treatment, there is an urgent need to identify reliable biomarkers and therapeutic targets to improve early detection and personalized therapy. The OAS (2'-5'-oligoadenylate synthetase) family genes, known for their roles in antiviral immunity, have emerged as potential regulators in cancer biology. This study aimed to explore the diagnostic and functional relevance of OAS family genes in breast cancer.

METHODOLOGY

Breast cancer cell lines and controls were cultured under specific conditions, and DNA and RNA were extracted for downstream analyses. RT-qPCR, bisulfite sequencing, and Western blotting were employed to assess gene expression, promoter methylation, and knockdown efficiency of OAS family genes. Functional assays, including CCK-8, colony formation, and wound healing, evaluated cellular behaviors, while bioinformatics tools (UALCAN, GEPIA, HPA, OncoDB, cBioPortal, and others) validated findings and explored correlations with clinical data.

RESULTS

The OAS family genes (OAS1, OAS2, OAS3, and OASL) were found to be significantly upregulated in breast cancer cell lines and tissues compared to normal controls. This overexpression was strongly associated with reduced promoter methylation. Receiver operating characteristic (ROC) analysis demonstrated high diagnostic accuracy, with area under the curve (AUC) values exceeding 0.93 for all four genes. Increased OAS expression correlated with advanced cancer stages and poor overall survival in breast cancer patients. Functional analysis revealed their involvement in critical biological processes, including immune modulation and oncogenic pathways. Silencing OAS genes in breast cancer cells significantly inhibited cell proliferation and colony formation, while unexpectedly enhancing migratory capacity. Additionally, correlations with immune cell infiltration, molecular subtypes, and drug sensitivity highlighted their potential roles in the tumor microenvironment and therapeutic response.

CONCLUSION

The findings of this study established OAS family genes as potential biomarkers and key players in breast cancer progression, offering promise as diagnostic biomarkers and therapeutic targets to address unmet clinical needs.

摘要

背景

乳腺癌是全球女性中最常见的恶性肿瘤,具有复杂的分子和细胞异质性。尽管在诊断和治疗方面取得了进展,但迫切需要确定可靠的生物标志物和治疗靶点,以改善早期检测和个性化治疗。OAS(2'-5'-寡腺苷酸合成酶)家族基因,因其在抗病毒免疫中的作用而闻名,已成为癌症生物学中的潜在调节因子。本研究旨在探讨OAS家族基因在乳腺癌中的诊断和功能相关性。

方法

乳腺癌细胞系和对照在特定条件下培养,提取DNA和RNA用于下游分析。采用RT-qPCR、亚硫酸氢盐测序和蛋白质免疫印迹法评估OAS家族基因的表达、启动子甲基化和敲低效率。功能测定,包括CCK-8、集落形成和伤口愈合,评估细胞行为,而生物信息学工具(UALCAN、GEPIA、HPA、OncoDB、cBioPortal等)验证研究结果并探索与临床数据的相关性。

结果

与正常对照相比,发现OAS家族基因(OAS1、OAS2、OAS3和OASL)在乳腺癌细胞系和组织中显著上调。这种过表达与启动子甲基化减少密切相关。受试者工作特征(ROC)分析显示诊断准确性高,所有四个基因的曲线下面积(AUC)值均超过0.93。OAS表达增加与乳腺癌患者的晚期癌症阶段和较差的总生存期相关。功能分析表明它们参与关键的生物学过程,包括免疫调节和致癌途径。在乳腺癌细胞中沉默OAS基因显著抑制细胞增殖和集落形成,同时意外地增强迁移能力。此外,与免疫细胞浸润、分子亚型和药物敏感性的相关性突出了它们在肿瘤微环境和治疗反应中的潜在作用。

结论

本研究结果确定OAS家族基因是乳腺癌进展中的潜在生物标志物和关键参与者,有望作为诊断生物标志物和治疗靶点来满足未满足的临床需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ab8/11619215/58784440924f/41065_2024_353_Fig1_HTML.jpg

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