研究动态
Articles below are published ahead of final publication in an issue. Please cite articles in the following format: authors, (year), title, journal, DOI.

膀胱癌免疫相关基因预后标志的开发以及潜在药物发现。

Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings.

发表日期:2023 Sep 23
作者: Zhang Xiaoqin, Lu Zhouqi, Pan Huan, Feng Xinyi, Shen Bin, Wu Jiming, Liu Shihui, Zhou Bangwei, Jin Jing, He Yi, Gao Jinlai
来源: Genes & Diseases

摘要:

膀胱癌是一种在尿系统中主要影响男性的常见恶性肿瘤。尽管与单纯手术相比,基于铂类的化疗已经证明在整体生存率方面有一定提高,但传统化疗药物的不良副作用影响了治疗效果。然而,免疫疗法在膀胱癌的治疗中表现出巨大潜力。本研究利用癌症基因组图谱数据库(TCGA)进行生物信息学分析,为膀胱癌建立了一个与免疫相关的预后特征。通过识别高风险组和低风险组之间的基因差异表达,利用连通性图谱数据库预测了一种潜在的治疗药物。随后,通过MTT测定和三维细胞培养技术验证了这种药物对T24细胞生长的影响。这个标志性特征包括1个免疫相关的长链非编码RNA(NR2F1-AS1)和16个免疫相关的mRNA(DEFB133、RBP7、PDGFRA、CGB3、PDGFD、SCG2、ADCYAP1R1、OPRL1、PGR、PSMD1、TANK、PRDX1、ADIPOR2、S100A8、AHNAK、EGFR)。根据风险评分的评估,病人被分为低风险和高风险的两个组别。低风险组的患者在生存方面表现出明显较高的概率。此外,这两个类别之间存在着免疫浸润的变化。通过分析基因表达的差异,发现了有可能的药物Cephaeline,它在抑制T24膀胱癌细胞的生存和生长方面显示出了希望。这种创新的预测模式可以高效地对膀胱癌患者进行分类,从而为那些预后较差的患者提供有针对性和严格的治疗。有可能的治疗药物的发现为膀胱癌的免疫疗法试验奠定了基础。©2023. 作者,由Springer Nature B.V.独家授权。
Bladder cancer, predominantly affecting men, is a prevalent malignancy of the urinary system. Although platinum-based chemotherapy has demonstrated certain enhancements in overall survival when compared to surgery alone, the efficacy of treatments is impeded by the unfavorable side effects of conventional chemotherapy medications. Nonetheless, immunotherapy exhibits potential in the treatment of bladder cancer.To create an immune-associated prognostic signature for bladder cancer, bioinformatics analyses were performed utilizing The Cancer Genome Atlas (TCGA) database in this study. By identifying differential gene expressions between the high-risk and low-risk groups, a potential therapeutic drug was predicted using the Connectivity Map database. Subsequently, the impact of this drug on the growth of T24 cells was validated through MTT assay and 3D cell culture techniques.The signature included 1 immune-associated LncRNA (NR2F1-AS1) and 16 immune-associated mRNAs (DEFB133, RBP7, PDGFRA, CGB3, PDGFD, SCG2, ADCYAP1R1, OPRL1, PGR, PSMD1, TANK, PRDX1, ADIPOR2, S100A8, AHNAK, EGFR). Based on the assessment of risk scores, the patients were classified into cohorts of low-risk and high-risk individuals. The cohort with low risk demonstrated a considerably higher likelihood of survival in comparison to the group with high risk. Furthermore, variations in immune infiltration were noted among the two categories. Cephaeline, a possible medication, was discovered by analyzing variations in gene expression. It exhibited promise in suppressing the viability and growth of T24 bladder cancer cells.The novel predictive pattern allows for efficient categorization of patients with bladder cancer, enabling focused and rigorous treatment for those expected to have a worse prognosis. The discovery of a possible curative medication establishes a basis for forthcoming immunotherapy trials in bladder cancer.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.