Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings
Development of a prognostic signature for immune-associated genes in bladder cancer and exploring potential drug findings
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DOI：
10.1007/s11255-023-03796-7
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发表时间：
2023-09-23
影响因子：
2
通讯作者：
Jinlai，Gao
中科院分区：
文献类型：
--
作者：
Xiaoqin，Zhang;Zhouqi，Lu;Jinlai，Gao
背景：膀胱癌是泌尿系统的一种常见恶性肿瘤，主要影响男性。尽管与单纯手术相比，以铂为基础的化疗在总生存率方面有一定的提高，但传统化疗药物的不良副作用阻碍了治疗的效果。尽管如此，免疫疗法在膀胱癌的治疗中显示出潜力。方法本研究利用癌症基因组图谱（TCGA）数据库进行生物信息学分析，建立膀胱癌免疫相关预后特征。通过识别高风险和低风险组之间的差异基因表达，使用Connectivity Map数据库预测潜在的治疗药物。随后，通过MTT实验和3D细胞培养技术验证该药物对T24细胞生长的影响。结果签名包括1个免疫相关LncRNA （NR2F1-AS1）和16个免疫相关mrna （DEFB133、RBP7、PDGFRA、CGB3、PDGFD、SCG2、ADCYAP1R1、OPRL1、PGR、PSMD1、TANK、PRDX1、ADIPOR2、S100A8、AHNAK、EGFR）。根据风险评分，将患者分为低危组和高危组。与高风险组相比，低风险组的生存可能性要高得多。此外，免疫浸润在两类之间也存在差异。通过分析基因表达的变化，发现了一种可能的药物头孢林。它显示出抑制T24膀胱癌细胞的活力和生长的希望。结论新的预测模式可以有效地对膀胱癌患者进行分类，从而对预后较差的患者进行集中和严格的治疗。一种可能的治疗药物的发现为即将进行的膀胱癌免疫治疗试验奠定了基础。
BackgroundBladder 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.MethodsTo 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.ResultsThe 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.ConclusionThe 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.