Martinou Eirini G, Moller-Levet Carla S, Angelidi Angeliki M
Hepatobiliary and Pancreatic Surgery Department, Royal Surrey County Hospital Guildford GU2 7XX, UK.
Faculty of Health and Medical Sciences, University of Surrey Guildford GU2 7XH, UK.
Am J Cancer Res. 2022 Feb 15;12(2):585-600. eCollection 2022.
Pre-B-cell leukaemia (PBX) is a transcription factor family ( and ) that regulates important cellular functions and has been identified to be involved in human cancers. This study aimed to explore the expression of genes and their clinical significance in colorectal cancer (CRC). We analysed the differential expression of genes in CRC vs. normal tissue, using the Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/) and ONCOMINE platform (https://www.oncomine.org/). The UALCAN (http://ualcan.path.uab.edu/) interactive OMICS web-server was used to evaluate the epigenetic regulation of genes via their promoter methylation status. We found that only was upregulated whereas and were downregulated (644 tumour vs. 51 normal samples) (P<0.001). The methylation status of promoter appeared to be decreased (P=1.4e-07) whereas the methylation status of and promoters was increased (P=3.8e-04 and P=3.2e-07, respectively) in cancer vs. normal samples. To determine the prognostic value of , we conducted a Kaplan-Meier survival analysis and multivariable COX regression. We observed that high expression was associated with increased risk for a worse overall survival (OS) in the TCGA CRC patient cohort (n=639), (HR 1.46, 95% CI 1.14-1.88, P=0.003) adjusted for age, gender, tumour location and metastases. We conducted in vitro gene expression modulation experiments to investigate the impact of overexpression in CRC cell (HCT116) growth. Additionally, we evaluated the RNA expression of epithelial-mesenchymal transition (EMT) and angiogenesis markers. studies showed that overexpression increased CRC cell proliferation (P<0.001) and upregulated the expression of EMT markers (P<0.05) and angiomarker (P<0.0001). Lastly, through the Cistrome data browser (http://dbtoolkit.cistrome.org/) we investigated putative transcriptional regulators and we performed gene set enrichment analysis in Enrichr server (https://maayanlab.cloud/Enrichr/) to identify related biological processes. Nineteen factors were identified to be putative regulators of and gene set enrichment analysis showed that biological processes related to cell cycle and cell proliferation were enriched (GO:0051726: , and , P=0.001). In conclusion, our study identified as a potential novel oncopromoter in CRC and its overexpression was found to be associated with increased risk for worse survival rate.
前B细胞白血病（PBX）是一个转录因子家族，它调节重要的细胞功能，并且已被确定与人类癌症有关。本研究旨在探讨[基因名称]基因在结直肠癌（CRC）中的表达及其临床意义。我们使用癌症基因组图谱（TCGA）（https://portal.gdc.cancer.gov/）和ONCOMINE平台（https://www.oncomine.org/）分析了[基因名称]基因在CRC与正常组织中的差异表达。UALCAN（http://ualcan.path.uab.edu/）交互式组学网络服务器用于通过其启动子甲基化状态评估[基因名称]基因的表观遗传调控。我们发现只有[基因名称1]上调，而[基因名称2]和[基因名称3]下调（644个肿瘤样本与51个正常样本）（P<0.001）。与正常样本相比，癌症样本中[基因名称1]启动子的甲基化状态似乎降低（P=1.4e-07），而[基因名称2]和[基因名称3]启动子的甲基化状态增加（分别为P=3.8e-04和P=3.2e-07）。为了确定[基因名称]的预后价值，我们进行了Kaplan-Meier生存分析和多变量COX回归。我们观察到，在TCGA CRC患者队列（n=639）中，高[基因名称]表达与总体生存期（OS）较差的风险增加相关（HR 1.46，95%CI 1.14-1.88，P=0.003），并对年龄、性别、肿瘤位置和转移进行了调整。我们进行了体外基因表达调节实验，以研究[基因名称]过表达对CRC细胞（HCT116）生长的影响。此外，我们评估了上皮-间质转化（EMT）和血管生成标志物的RNA表达。[相关实验]研究表明，[基因名称]过表达增加了CRC细胞增殖（P<0.001），并上调了EMT标志物[标志物名称1]（P<0.05）和血管生成标志物[标志物名称2]（P<0.0001）的表达。最后，通过Cistrome数据浏览器（http://dbtoolkit.cistrome.org/），我们研究了假定的转录调节因子，并在Enrichr服务器（https://maayanlab.cloud/Enrichr/）中进行了基因集富集分析，以识别相关的生物学过程。19个因子被确定为[基因名称]的假定调节因子，基因集富集分析表明与细胞周期和细胞增殖相关的生物学过程得到了富集（GO:0051726:[相关生物学过程1]、[相关生物学过程2]和[相关生物学过程3]，P=0.001）。总之，我们的研究确定[基因名称]是CRC中一种潜在的新型癌基因启动子，发现其过表达与较差生存率风险增加相关。
