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不同组织学亚型非小细胞肺癌中基因组改变和重金属的差异。

Differences of genomic alterations and heavy metals in non-small cell lung cancer with different histological subtypes.

机构信息

Department of Oncology, Affiliated Hospital of Chengde Medical University, Chengde, 067000, China.

Shanghai Zhangjiang Institute of Medical Innovation, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai, 200135, China.

出版信息

J Cancer Res Clin Oncol. 2023 Sep;149(12):9999-10013. doi: 10.1007/s00432-023-04929-2. Epub 2023 May 31.

Abstract

PURPOSE

This study aimed to explore the correlations among heavy metals concentration, histologic subtypes and molecular characteristics in patients with non-small cell lung cancer (NSCLC).

METHODS

In this study, an NGS panel of 82 tumor-associated genes was used to identify genomic alternations in 180 newly diagnosed patients with NSCLC. The concentrations of 18 heavy metals in the serum samples were detected by inductively coupled plasma emission spectrometry (ICP-MS).

RESULTS

A total of 243 somatic mutations of 25 mutant genes were identified in 115 of 148 patients with LUAD and 45 somatic mutations of 15 mutant genes were found in 24 of 32 patients with LUSC. The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were markedly different between patients with LUAD and LUSC. Moreover, patients with LUSC were significantly positively correlated with Ba, but not LUAD. Lastly, patients with EGFR mutations presented significant negative correlations with Cd and Sr, whereas patients with TP53 mutations showed a significant positive correlation with Pb.

CONCLUSION

The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were different between patients with LUAC and LUSC, and heavy metals (e.g., Ba, Pb, and Cd) may contribute to the tumorigenesis of NSCLC with different histological and molecular subtypes.

摘要

目的

本研究旨在探讨非小细胞肺癌(NSCLC)患者体内重金属浓度、组织学亚型和分子特征之间的相关性。

方法

在这项研究中,我们使用了一个包含 82 个肿瘤相关基因的 NGS 面板,对 180 名新诊断的 NSCLC 患者进行了基因组改变的鉴定。采用电感耦合等离子体发射光谱法(ICP-MS)检测血清样本中 18 种重金属的浓度。

结果

在 148 名 LUAD 患者中的 115 名和 32 名 LUSC 患者中的 24 名患者中,共发现了 25 个突变基因的 243 个体细胞突变和 15 个突变基因的 45 个体细胞突变。LUAD 和 LUSC 患者之间的基因组改变、体细胞相互作用、传统血清生物标志物和重金属明显不同。此外,LUSC 患者与 Ba 呈显著正相关,而 LUAD 患者则无此相关性。最后,EGFR 突变患者与 Cd 和 Sr 呈显著负相关,而 TP53 突变患者与 Pb 呈显著正相关。

结论

LUAC 和 LUSC 患者之间的基因组改变、体细胞相互作用、传统血清生物标志物和重金属明显不同,重金属(如 Ba、Pb 和 Cd)可能有助于不同组织学和分子亚型的 NSCLC 的肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bf2/11798269/8db7004b51df/432_2023_4929_Fig1_HTML.jpg

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