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基于生物信息学筛选酪氨酸激酶抑制剂耐药性肺腺癌转化为小细胞肺癌的关键基因

Bioinformatics-based screening of key genes for transformation of tyrosine kinase inhibitor-resistant lung adenocarcinoma to small cell lung cancer.

作者信息

Zhang Ying, Chen Qiang, Huang Ting, Zhu Di, Lu Yuanzhi

机构信息

Department of Oncology, First Affiliated Hospital of Jinan University, Guangzhou, China.

Department of Clinical Pathology, First Affiliated Hospital of Jinan University, Guangzhou, China.

出版信息

Front Med (Lausanne). 2023 Jul 31;10:1203461. doi: 10.3389/fmed.2023.1203461. eCollection 2023.

DOI:10.3389/fmed.2023.1203461
PMID:37583423
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10424445/
Abstract

PURPOSE

Lung adenocarcinoma (LUAD) is a common type of lung cancer. Cancer in a small number of patients with EGFR mutations will transform from LUAD to small cell lung cancer (SCLC) during epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapiesr. The purpose of the present study was to identify the core genes related to the transformation of LUAD into SCLC and to explore the associated molecular mechanisms.

METHODS

GSE29016, GSE1037, GSE6044 and GSE40275 mRNA microarray datasets from Gene Expression Omnibus (GEO) were analyzed to obtain differentially expressed genes (DEGs) between LUAD and SCLC tissues, and the results were used for network analysis of protein-protein interactions (PPIs). After identifying the hub gene by STRING and Cytoscape platform, we explored the relationship between hub genes and the occurrence and development of SCLC. Finally, the obtained hub genes were validated in treated LUAD cells.

RESULTS

A total of 41 DEGs were obtained, four hub genes (, , and ) were identified, and related prognostic information was obtained. The coexpressed genes of the hub gene set were further screened, and the analysis identified many genes related to the cell cycle. Subsequently, LUAD cell models with TP53 and RB1 inactivation and overexpression of ASCL1 were constructed, and then the expression of hub genes was detected, the results showed that the four hub genes were all elevated in the established cell model.

CONCLUSION

, , and may affect the transformation of LUAD to SCLC and represent new candidate molecular markers for the occurrence and development of SCLC.

摘要

目的

肺腺癌（LUAD）是肺癌的常见类型。少数表皮生长因子受体（EGFR）突变的患者在表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）治疗期间，其癌症会从肺腺癌转变为小细胞肺癌（SCLC）。本研究的目的是确定与肺腺癌转变为小细胞肺癌相关的核心基因，并探讨相关的分子机制。

方法

分析来自基因表达综合数据库（GEO）的GSE29016、GSE1037、GSE6044和GSE40275 mRNA微阵列数据集，以获得肺腺癌和小细胞肺癌组织之间的差异表达基因（DEG），并将结果用于蛋白质-蛋白质相互作用（PPI）的网络分析。通过STRING和Cytoscape平台鉴定出枢纽基因后，我们探讨了枢纽基因与小细胞肺癌发生发展的关系。最后，在经处理的肺腺癌细胞中验证获得的枢纽基因。

结果

共获得41个差异表达基因，鉴定出4个枢纽基因（、、和），并获得了相关的预后信息。进一步筛选枢纽基因集的共表达基因，分析确定了许多与细胞周期相关的基因。随后，构建了TP53和RB1失活且ASCL1过表达的肺腺癌细胞模型，然后检测枢纽基因的表达，结果表明在建立的细胞模型中这4个枢纽基因均升高。

结论

、、和可能影响肺腺癌向小细胞肺癌的转变，并代表小细胞肺癌发生发展的新候选分子标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/fc1e8a1518bf/fmed-10-1203461-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/502521e9df3e/fmed-10-1203461-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/40543c070bbe/fmed-10-1203461-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/77f86851bba4/fmed-10-1203461-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/9e128af58f14/fmed-10-1203461-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/0b217de33bc8/fmed-10-1203461-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/7e889e237286/fmed-10-1203461-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/fc1e8a1518bf/fmed-10-1203461-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/502521e9df3e/fmed-10-1203461-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/40543c070bbe/fmed-10-1203461-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/77f86851bba4/fmed-10-1203461-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/9e128af58f14/fmed-10-1203461-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/0b217de33bc8/fmed-10-1203461-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/7e889e237286/fmed-10-1203461-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2dd/10424445/fc1e8a1518bf/fmed-10-1203461-g007.jpg

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