Qian Duocheng, Wang Xin'an, Lv Tengfei, Li Dujian, Chen Xi
Department of Urology, School of Medicine, Shanghai Fourth People's Hospital, Tongji University, 1279 Sanmen Road, Shanghai, 200081, China.
Department of Urology, School of Medicine, Tongji Hospital, Tongji University, 389 Xincun Road, Shanghai, 200065, China.
Discov Oncol. 2024 Dec 3;15(1):741. doi: 10.1007/s12672-024-01645-2.
The morbidity and mortality rates of prostate cancer (PCa) are high among elderly men worldwide. Several factors, such as heredity, obesity, and environment are associated with the occurrence of PCa. Cigarette smoking, which is also an important factor in the development of PCa, can lead to genetic alterations and consequently promote PCa development. However, the smoking-induced genetic alterations in PCa are unclear. This study aimed to identify the potential smoking-related genes associated with PCa development. The smoking-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus (GEO) which included lots of PCa datasets. DEGs were subjected to protein-protein interaction (PPI) network analysis to identify the hub genes. The pathways in which these hub genes were enriched were identified. The Cancer Genome Atlas (TCGA) dataset was used to examine the expression of smoking-related genes in PCa samples and estimate their value in predicting tumor progression and prognosis. In total, 110 smoking-related DEGs were got from GSE68135 dataset which included microarray data of PCa patients with smoking or not and 14 smoking-related key genes associated with PCa were identified from PPI network. The expression of the following seven key genes was altered in TCGA PCa patients: EWSR1, SRSF6, COL6A3, FBLN1, DCN, CYP2J2, and PLA2G2A. EWSR1, SRSF6, FBLN1, and CYP2J2 also influenced PCa progression. Additionally, EWSR1 influenced disease-free survival. In the logistic regression model, CYP2J2, which exhibited the highest risk scores, was identified as the risk gene for PCa. We also found one of the smoking-related genes: EWSR1 was truly upregulated in clinical PCa patients and influenced PCa cells invasion and proliferation. This study identified the function of smoking-related genes involved in the progression of PCa.
在全球老年男性中，前列腺癌（PCa）的发病率和死亡率都很高。遗传、肥胖和环境等多种因素与PCa的发生有关。吸烟也是PCa发生发展的一个重要因素，它可导致基因改变，进而促进PCa的发展。然而，吸烟诱导的PCa基因改变尚不清楚。本研究旨在鉴定与PCa发生发展相关的潜在吸烟相关基因。利用包含大量PCa数据集的基因表达综合数据库（GEO）来鉴定吸烟相关的差异表达基因（DEG）。对DEG进行蛋白质-蛋白质相互作用（PPI）网络分析以鉴定枢纽基因。鉴定出这些枢纽基因富集的通路。使用癌症基因组图谱（TCGA）数据集来检测PCa样本中吸烟相关基因的表达，并评估它们在预测肿瘤进展和预后方面的价值。从GSE68135数据集中总共获得了110个吸烟相关的DEG，该数据集包含吸烟或不吸烟的PCa患者芯片数据，并且从PPI网络中鉴定出14个与PCa相关的吸烟相关关键基因。在TCGA的PCa患者中，以下七个关键基因的表达发生了改变：EWSR1、SRSF6、COL6A3、FBLN1、DCN、CYP2J2和PLA2G2A。EWSR1、SRSF6、FBLN1和CYP2J2也影响PCa的进展。此外，EWSR1影响无病生存期。在逻辑回归模型中，风险评分最高的CYP2J2被鉴定为PCa的风险基因。我们还发现吸烟相关基因之一：EWSR1在临床PCa患者中确实上调，并影响PCa细胞的侵袭和增殖。本研究确定了吸烟相关基因在PCa进展中的作用。
