基于数据挖掘的肺腺癌和鳞癌鉴别潜能的表观遗传特征识别。

Data mining-based identification of epigenetic signatures with discrimination potential of lung adenocarcinoma and squamous cell carcinoma.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.

Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, China.

出版信息

Mol Biol Rep. 2024 Feb 1;51(1):255. doi: 10.1007/s11033-024-09216-y.

DOI:10.1007/s11033-024-09216-y

PMID:38302782

Abstract

BACKGROUND

Mounting evidence suggests that lung adenocarcinoma (LAC) and lung squamous cell carcinoma (LSC) have different biological behaviors and therapeutic regimens in clinical practice. However, limited improvements in molecular differential diagnosis of the two entities have been achieved in recent decades. We aimed to find novel markers that could define non-small cell lung cancer (NSCLC) subtypes.

METHODS

We first explored publically available databases to search for DNA methylation signatures that enable a precise discrimination of LAC and LSC. Next-generation sequencing (NGS) was then used to analyze the methylation status and sites of candidate genes in LAC/LSC tissue samples, and a quantitative methylation-sensitive PCR (qMS-PCR) assay was conducted to test the performance of the selected maker in tissue samples and bronchoalveolar lavage fluid (BALF) specimens.

RESULTS

We screened 19 top-ranked methylation loci that are differentially methylated between LAC and LSC. Among these hits, 6 methylation sites are enriched within the PREX1 gene promoter, thus becoming our focus. NGS analysis confirmed markedly higher PREX1 methylation levels in LAC than in LSC and revealed the right sites for detection of PREX1 methylation. Furthermore, PREX1 methylation analysis in lung cancer tissue samples defined 9 of 11 pathologically proven LACs, as well as 12 of 14 LSCs. In addition, ~ 80% LAC BALF samples showed methylated PREX1 compared to substantially lower test positivity (0-9%) of it in LSC and other lung conditions (P < 0.01).

CONCLUSION

Our pilot study identified a unique epigenetic signature that could effectively distinguish LAC from LSC in various lung samples. It may enhance our in-depth understanding of the biology of lung cancer and pave the way for better accurate diagnosis and treatment stratification in the future.

摘要

背景

越来越多的证据表明，肺腺癌（LAC）和肺鳞状细胞癌（LSC）在临床实践中有不同的生物学行为和治疗方案。然而，近几十年来，这两种实体在分子鉴别诊断方面的进展有限。我们旨在寻找新的标志物，以定义非小细胞肺癌（NSCLC）亚型。

方法

我们首先探索了公开可用的数据库，以寻找能够精确区分 LAC 和 LSC 的 DNA 甲基化特征。然后，使用下一代测序（NGS）分析 LAC/LSC 组织样本中候选基因的甲基化状态和位点，并进行定量甲基化敏感 PCR（qMS-PCR）检测以测试所选标志物在组织样本和支气管肺泡灌洗液（BALF）标本中的性能。

结果

我们筛选了 19 个在 LAC 和 LSC 之间差异甲基化的顶级甲基化基因座。在这些命中中，6 个甲基化位点在 PREX1 基因启动子内富集，因此成为我们的重点。NGS 分析证实，LAC 中 PREX1 的甲基化水平明显高于 LSC，并揭示了检测 PREX1 甲基化的正确位点。此外，肺癌组织样本中的 PREX1 甲基化分析定义了 11 个经病理证实的 LAC 中的 9 个，以及 14 个 LSC 中的 12 个。此外，与 LSC 和其他肺部疾病（P<0.01）相比，约 80%的 LAC BALF 样本显示 PREX1 甲基化。