Ma Chunxu, Zhao Jihua, Wu Ying, Wang Jun, Wang Hao
Department of Nuclear Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
College of Physical Education, Yunnan Agricultural University, Kunming, Yunnan 650201, P.R. China.
Oncol Lett. 2022 May 16;24(1):209. doi: 10.3892/ol.2022.13330. eCollection 2022 Jul.
The diagnosis of small cell lung carcinoma (SCLC) remains a great challenge. Changes in chromosome 3p (chr3) genes are usually observed in the pathogenesis of lung cancer, which suggests that these chr3 genes may be a diagnostic marker in the early stage of SCLC. The present study explored the diagnostic value of the chr3 gene in SCLC using Bioinformatics. Furthermore, reverse transcription-quantitative PCR (RT-qPCR) was used to reveal the expression patterns of diagnostic biomarkers in human pulmonary alveolar epithelial cells and in the SCLC cell line NCI-H146. A total of 33 differentially expressed (DE) chr3 genes and 1,156 module genes associated with clinical features of patients with SCLC were identified and functional enrichment analysis indicated that all these genes were significantly enriched in cell cycle terms. The area under the receiver operating characteristic curve demonstrated that the overlapping genes of the DE-chr3 and module genes, namely cell division cycle 25 A (CDC25A), FYVE and coiled-coil domain autophagy adaptor 1 (FYCO1) and lipid raft linker 1 (RFTN1), were relatively accurate in distinguishing normal from SCLC samples, and may thus be considered diagnostic biomarkers. CDC25A was overexpressed in SCLC samples, while FYCO1 and RFTN1 were highly expressed in normal samples, as evidenced by the RT-qPCR results. Single-gene gene set enrichment analysis suggested that the diagnostic biomarkers were significantly associated with cell cycle, ATP-binding cassette transporter, immune cell differentiation, immune response and multiple respiratory disease pathways. Furthermore, a total of 141 drugs were predicted by The Comparative Toxicogenomics Database to be able to modulate the expression of the diagnostic biomarkers, of which 8 drugs were shared among the three aforementioned diagnostic biomarkers. The present study identified three novel and powerful diagnostic biomarkers for SCLC based on chr3 genes. Suggestions for the development and selection of drugs for clinical treatment based on diagnostic biomarkers were also provided.
小细胞肺癌（SCLC）的诊断仍然是一项巨大挑战。3号染色体（chr3）基因的改变在肺癌发病机制中通常可见，这表明这些chr3基因可能是SCLC早期阶段的诊断标志物。本研究利用生物信息学探索chr3基因在SCLC中的诊断价值。此外，采用逆转录定量PCR（RT-qPCR）揭示诊断生物标志物在人肺泡上皮细胞和SCLC细胞系NCI-H146中的表达模式。共鉴定出33个差异表达（DE）的chr3基因和1156个与SCLC患者临床特征相关的模块基因，功能富集分析表明所有这些基因在细胞周期术语中均显著富集。受试者工作特征曲线下面积表明，DE-chr3和模块基因的重叠基因，即细胞分裂周期25A（CDC25A）、FYVE和卷曲螺旋结构域自噬衔接蛋白1（FYCO1）以及脂筏连接蛋白1（RFTN1），在区分正常样本和SCLC样本方面相对准确，因此可被视为诊断生物标志物。RT-qPCR结果显示，CDC25A在SCLC样本中过表达，而FYCO1和RFTN1在正常样本中高表达。单基因基因集富集分析表明，诊断生物标志物与细胞周期、ATP结合盒转运蛋白、免疫细胞分化、免疫反应和多种呼吸系统疾病途径显著相关。此外，比较毒理基因组学数据库预测共有141种药物能够调节诊断生物标志物的表达，其中8种药物在上述三种诊断生物标志物中共有。本研究基于chr3基因鉴定出三种新型且强大的SCLC诊断生物标志物。还提供了基于诊断生物标志物进行临床治疗药物开发和选择的建议。
