Alghamdi Rana A, Al-Zahrani Maryam H
Department of Chemistry, Science and Arts College, King Abdulaziz University, Rabigh, Saudi Arabia.
Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Saudi J Biol Sci. 2023 Apr;30(4):103596. doi: 10.1016/j.sjbs.2023.103596. Epub 2023 Feb 11.
Lung Squamous Cell Carcinoma (LUSC) is a major subtype of lung malignancies and is associated with the cause of cancer-mediated mortality worldwide. However, identification of transcriptomic signatures associated with survival-prognosis and immunity of tumor remains lacking.
The GSE2088, GSE6044, GSE19188, GSE21933, GSE33479, GSE33532, and GSE74706 were integrated for identifying differentially expressed genes (DEGs) with combined effect sizes. Also, the TCGA LUSC cohort was used for further analysis. A series of bioinformatics methods were utilized for conducting the whole study.
The 831 genes (such as and ) were found upregulated and the 731 genes (such as and ) were downregulated in the LUSC. The functional enrichment analysis identifies the upregulated KEGG pathways, including cell cycle, DNA replication, base excision repair, proteasome, mismatch repair, and cellular senescence. Also, the key hub genes (such as and ) were identified along with the eight gene modules that were significantly related to the protein-protein interaction (PPI) The clinical analyses identified that the overexpression group of and are substantially associated with a poor survival prognosis and the downregulated group of showed a similar trend. Moreover, our investigation demonstrated that the survival-associated genes were correlated with the stromal and immune scores in LUSC, indicating that the survival-associated genes regulate tumor immunity. The survival-associated genes were genetically altered in 27% of LUSC patients and showed excellent diagnostic efficiency. Finally, the consistent expression level of and were found in the TCGA LUSC cohort.
The identification of key transcriptomic signatures can be elucidated by the crucial mechanism of LUSC carcinogenesis.
肺鳞状细胞癌（LUSC）是肺恶性肿瘤的主要亚型，与全球癌症介导的死亡原因相关。然而，仍缺乏与肿瘤生存预后和免疫相关的转录组特征的鉴定。
整合GSE2088、GSE6044、GSE19188、GSE21933、GSE33479、GSE33532和GSE74706以鉴定具有联合效应大小的差异表达基因（DEG）。此外，使用TCGA LUSC队列进行进一步分析。采用一系列生物信息学方法进行整个研究。
在LUSC中发现831个基因（如 和 ）上调，731个基因（如 和 ）下调。功能富集分析确定了上调的KEGG通路，包括细胞周期、DNA复制、碱基切除修复、蛋白酶体、错配修复和细胞衰老。此外，还鉴定了关键枢纽基因（如 和 ）以及与蛋白质-蛋白质相互作用（PPI）显著相关的八个基因模块。临床分析表明， 和 的过表达组与较差的生存预后显著相关，而下调组也呈现类似趋势。此外，我们的研究表明，生存相关基因与LUSC中的基质和免疫评分相关，表明生存相关基因调节肿瘤免疫。生存相关基因在27%的LUSC患者中发生基因改变，并显示出优异的诊断效率。最后，在TCGA LUSC队列中发现了 和 的一致表达水平。
关键转录组特征的鉴定可以通过LUSC致癌的关键机制来阐明。
