Table_1_A comprehensive role evaluation and mechanism exploration of POGLUT2 in pan-cancer.csv

ObjectiveTo evaluate the role of POGLUT2 in pan-cancer through bioinformatics analysis and experimental verification.MethodsExpression, gene mutation and amplification, methylation, and copy number alteration (CNA) of POGLUT2 were evaluated using The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx) databases. Moreover, POGLUT2 on survival and disease progression in pan-cancer was performed using TCGA data. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuneScore, ImmuCellAI, and TIMER databases. POGLUT2 correlated drug resistance analysis was performed using the GDSC2 database. Furthermore, POGLUT2 knockdown of breast cancer cells was established, followed by in vitro biological function assays and in vivo tumor growth study. The mechanisms of POGLUT2 in breast cancer were briefly evaluated via its connection with Notch signaling.ResultsIncreased levels of POGLUT2 were found in multiple types of cancer tissues and cell lines. Moreover, increased gene mutation and amplification, methylation, and CNA of POGLUT2 were found in several types of cancers. POGLUT2 was mainly expressed in stromal cells as verified by StromalScore, ESTIMATEScore, ImmuneScore, and Tumor purity, and POGLUT2 was positively correlated with cancer-associated fibroblasts, macrophages, monocytes, and neutrophils in the tumor microenvironment. In vitro and in vivo results showed that POGLUT2 knockdown could delay tumor growth and progression. Notch signaling components were related to the function of POGLUT2.ConclusionsIncreased levels of POGLUT2 could result in the dysregulated immune cell infiltration and tumor microenvironment and showed a significant regulatory effect on the progression of breast cancer through Notch-related signaling.

目的：通过生物信息学分析和实验验证，评估POGLUT2在泛癌中的作用。方法：利用癌症基因组图谱（TCGA）、癌症细胞系百科全书（CCLE）和基因型-组织表达（GTEx）数据库，对POGLUT2的表达、基因突变和扩增、甲基化和拷贝数改变（CNA）进行了评估。此外，使用TCGA数据对POGLUT2在泛癌中对生存和疾病进展的影响进行了分析。通过免疫评分、ImmuCellAI和TIMER数据库对免疫浸润和肿瘤微环境进行了评估。使用GDSC2数据库进行了POGLUT2相关耐药性分析。进一步地，建立了乳腺癌细胞的POGLUT2敲低模型，随后进行了体外生物学功能检测和体内肿瘤生长研究。通过POGLUT2与Notch信号通路的关系，简要评估了POGLUT2在乳腺癌中的作用机制。结果：在多种癌症组织和细胞系中发现了POGLUT2水平的增加。此外，在多种癌症中发现了POGLUT2的基因突变和扩增、甲基化和CNA的增加。通过StromalScore、ESTIMATEScore、免疫评分和肿瘤纯度验证，POGLUT2主要在间质细胞中表达，并且POGLUT2与肿瘤微环境中的癌症相关成纤维细胞、巨噬细胞、单核细胞和中性粒细胞呈正相关。体外和体内结果表明，POGLUT2敲低可以延缓肿瘤的生长和进展。Notch信号通路成分与POGLUT2的功能相关。结论：POGLUT2水平的增加可能导致免疫细胞浸润和肿瘤微环境的失调，并通过Notch相关信号通路对乳腺癌的进展产生显著的调控作用。