Uşak University, School of Medicine, Department of Medical Biology, Uşak, Türkiye.
Nigde Omer Halisdemir University, School of Medicine, Department of Medical Biology, Niğde, Türkiye.
Immunobiology. 2024 Sep;229(5):152838. doi: 10.1016/j.imbio.2024.152838. Epub 2024 Jul 26.
Twenty to thirty percent of non-small cell lung cancers (NSCLC) are caused by lung squamous cell carcinoma (LUSC), especially in smokers and there has been limited study previously evaluating the situation in terms of the genome and gene expression profile, which demonstrates the relationship among DEL-1, leucocyte recruitment, and pro-inflammatory cytokines in LUSC.
In the current study, the m-RNA expression patterns and mutation profiles of our target genes, such as, pro-inflammatory cytokines, chemoattractant molecules, and DEL-1 genes, in 511 LUSC patients. To find the harmful mutations, the PolyPhen-2 and SNAP programs were employed. Not only gene expression was detected, but also survival analysis and correlation between DEL-1 and other target genes' expression levels were explored too.
Target genes such as, DEL-1, TNF, IL-18, IL-1, CXCL8, CXCL13, and IL-6 were found to have a total genetic anomaly carrying rate of 16.4%. Seven mutations were found, and two of those mutations have a pathogenic aspect. Deep deletion and gene amplification of the genetic anomalies were also observed. According to gene expression analysis results in the LUSC patient group; DEL-1 and IL-6 levels were significantly lower than those of the control group, whereas the CXCL13 level was found to be higher.
Findings of the current study revealed that, there is a significant role of DEL-1 in LUSC pathogenesis. Since present study is an in silico-centered study, this approach can give more insight on experimental studies. These events may support that one of the cancer improvement mechanisms depending on DEL-1 gene at the molecular level.
20%至 30%的非小细胞肺癌（NSCLC）是由肺鳞状细胞癌（LUSC）引起的，尤其是在吸烟者中，之前很少有研究评估其基因组和基因表达谱的情况，这表明了 DEL-1、白细胞募集和 LUSC 中的促炎细胞因子之间的关系。
在目前的研究中，我们检测了 511 名 LUSC 患者的目标基因（如促炎细胞因子、趋化因子分子和 DEL-1 基因）的 m-RNA 表达模式和突变谱。为了找到有害突变，使用了 PolyPhen-2 和 SNAP 程序。不仅检测了基因表达，还进行了生存分析，并探讨了 DEL-1 与其他目标基因表达水平之间的相关性。
DEL-1、TNF、IL-18、IL-1、CXCL8、CXCL13 和 IL-6 等目标基因被发现总遗传异常携带率为 16.4%。发现了 7 种突变，其中 2 种具有致病性。还观察到遗传异常的深度缺失和基因扩增。根据 LUSC 患者组的基因表达分析结果，DEL-1 和 IL-6 水平明显低于对照组，而 CXCL13 水平则较高。
本研究的结果表明，DEL-1 在 LUSC 的发病机制中起重要作用。由于本研究是一种基于计算机的研究，这种方法可以为实验研究提供更多的见解。这些事件可能支持在分子水平上依赖 DEL-1 基因的癌症改善机制之一。
