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多组学研究揭示 BTG2 是早期非小细胞肺癌的可靠预后标志物。

A multi-omic study reveals BTG2 as a reliable prognostic marker for early-stage non-small cell lung cancer.

机构信息

Department of Biostatistics, School of Public Health, Nanjing Medical University, China.

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.

出版信息

Mol Oncol. 2018 Jun;12(6):913-924. doi: 10.1002/1878-0261.12204. Epub 2018 May 4.

Abstract

B-cell translocation gene 2 (BTG2) is a tumour suppressor protein known to be downregulated in several types of cancer. In this study, we investigated a potential role for BTG2 in early-stage non-small cell lung cancer (NSCLC) survival. We analysed BTG2 methylation data from 1230 early-stage NSCLC patients from five international cohorts, as well as gene expression data from 3038 lung cancer cases from multiple cohorts. Three CpG probes (cg01798157, cg06373167, cg23371584) that detected BTG2 hypermethylation in tumour tissues were associated with lower overall survival. The prognostic model based on methylation could distinguish patient survival in the four cohorts [hazard ratio (HR) range, 1.51-2.21] and the independent validation set (HR = 1.85). In the expression analysis, BTG2 expression was positively correlated with survival in each cohort (HR range, 0.28-0.68), which we confirmed with meta-analysis (HR = 0.61, 95% CI 0.54-0.68). The three CpG probes were all negatively correlated with BTG2 expression. Importantly, an integrative model of BTG2 methylation, expression and clinical information showed better predictive ability in the training set and validation set. In conclusion, the methylation and integrated prognostic signatures based on BTG2 are stable and reliable biomarkers for early-stage NSCLC. They may have new applications for appropriate clinical adjuvant trials and personalized treatments in the future.

摘要

B 细胞易位基因 2(BTG2)是一种肿瘤抑制蛋白,已知在几种类型的癌症中下调。在这项研究中,我们研究了 BTG2 在早期非小细胞肺癌(NSCLC)生存中的潜在作用。我们分析了来自五个国际队列的 1230 例早期 NSCLC 患者的 BTG2 甲基化数据,以及来自多个队列的 3038 例肺癌病例的基因表达数据。三个 CpG 探针(cg01798157、cg06373167、cg23371584)检测到肿瘤组织中 BTG2 高甲基化,与总生存期降低相关。基于甲基化的预后模型可以区分四个队列中的患者生存情况[风险比(HR)范围为 1.51-2.21]和独立验证集(HR=1.85)。在表达分析中,BTG2 表达与每个队列的生存呈正相关(HR 范围为 0.28-0.68),我们通过荟萃分析得到了证实(HR=0.61,95%CI 0.54-0.68)。这三个 CpG 探针均与 BTG2 表达呈负相关。重要的是,BTG2 甲基化、表达和临床信息的综合模型在训练集和验证集中显示出更好的预测能力。总之,基于 BTG2 的甲基化和综合预后标志物是早期 NSCLC 的稳定可靠的生物标志物。它们可能在未来为适当的临床辅助试验和个性化治疗提供新的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6178/5983115/67f732270160/MOL2-12-913-g001.jpg

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