Zeng Fan-Rui, Zhou Xu-Yang, Zeng Ling-Ge, Sun Jian-Cong, He Fen, Mo Wei, Wen Yang, Wang Shu-Yu, Liu Qin, Guo Lin-Lang
Department of Radiation Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Pathology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
Ann Transl Med. 2022 Sep;10(18):968. doi: 10.21037/atm-22-3642.
Small cell lung cancer (SCLC), the most malignant of all the lung cancer subtypes, is characterized by drug resistance. This study sought to explore the key genes and pathways associated with the chemoresistance of SCLC.
The drug sensitivity of chemosensitive and chemoresistance SCLC cell lines was measured by Cell Counting Kit-8 assays. The total RNA from chemosensitive cell line H69 and chemoresistance cell line H69AR cells was extracted and subjected to messenger RNA (mRNA) and long non-coding RNA (lncRNA) microarray analyses. The differentially expressed genes (DEGs) and the differentially expressed lncRNAs (DELs) were screened out with a threshold of a |log fold change | ≥1 and an adjusted P value <0.05. A protein-protein interaction network was constructed, and hub genes were screened out. A lncRNA-mRNA co-expression network was also constructed. Gene Ontology and Kyoto Encyclopedia of Genes, Genomes enrichment analyses and Cis-regulatory element analyses were conducted on the DEGs and the top 10 upregulated DEL-co-expressed DEGs. The expression of the key genes was further analyzed in the GSE149507 data set and validated in H69/H69AR and H446/H446DDP cells by quantitative polymerase chain reaction assays.
The microarray results showed that a total of 609 mRNAs and 394 lncRNAs were differentially expressed in the chemoresistant SCLC cells. The mammalian target of rapamycin (mTOR) signaling pathway was enriched among the DEGs, the top 10 upregulated DEL-co-expressed DEGs, and the -co-expressed DEGs, which included , , , , , and . , , and were downregulated, and was upregulated in the SCLC tumor tissues in the GSE149507 data set. Further, , , 1, and were lowlier expressed and and were more highly expressed in the chemoresistant cells than sensitive cells.
The top 10 upregulated DELs containing may be involved in the regulation of drug resistance in SCLC. These DELs may regulate the genes related to the mTOR signaling pathway. These genes may also be biomarkers and potential targets for the treatment of SCLC.
小细胞肺癌（SCLC）是所有肺癌亚型中恶性程度最高的，具有耐药性。本研究旨在探索与SCLC化疗耐药相关的关键基因和通路。
采用细胞计数试剂盒-8法检测化疗敏感和耐药SCLC细胞系的药物敏感性。提取化疗敏感细胞系H69和耐药细胞系H69AR细胞的总RNA，进行信使核糖核酸（mRNA）和长链非编码核糖核酸（lncRNA）微阵列分析。以|log倍数变化|≥1且校正P值<0.05为阈值筛选差异表达基因（DEG）和差异表达lncRNA（DEL）。构建蛋白质-蛋白质相互作用网络，并筛选出枢纽基因。还构建了lncRNA-mRNA共表达网络。对DEG和前10个上调的DEL共表达DEG进行基因本体论和京都基因与基因组百科全书富集分析以及顺式调控元件分析。通过定量聚合酶链反应分析在GSE149507数据集中进一步分析关键基因的表达，并在H69/H69AR和H446/H446DDP细胞中进行验证。
微阵列结果显示，耐药SCLC细胞中共有609个mRNA和394个lncRNA差异表达。雷帕霉素哺乳动物靶标（mTOR）信号通路在DEG、前10个上调的DEL共表达DEG和共表达DEG中富集，其中包括 、 、 、 、 、 和 。在GSE149507数据集中，SCLC肿瘤组织中 、 、 和 下调， 上调。此外，与敏感细胞相比，耐药细胞中 、 、 和 表达较低， 和 表达较高。
包含 的前10个上调的DEL可能参与SCLC耐药性的调控。这些DEL可能调节与mTOR信号通路相关的基因。这些基因也可能是SCLC治疗的生物标志物和潜在靶点。
