Bioinformatics Analysis Combined With Experiments Predicts PUDP as a Potential Prognostic Biomarker for Hepatocellular Carcinoma Through Its Interaction With Tumor Microenvironment.
Bioinformatics Analysis Combined With Experiments Predicts PUDP as a Potential Prognostic Biomarker for Hepatocellular Carcinoma Through Its Interaction With Tumor Microenvironment.
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生物信息学分析与实验相结合，通过与肿瘤微环境的相互作用预测 PUDP 作为肝细胞癌的潜在预后生物标志物
DOI：
10.3389/fonc.2022.830174
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发表时间：
2022
影响因子：
4.7
通讯作者：
Han Y
中科院分区：
文献类型：
--
作者：
Yu J;Zhang W;Ding D;Hu Y;Guo G;Wang J;Han Y
肝细胞癌是世界上最致命的肿瘤之一，以预后差而臭名昭著。越来越多的证据表明，假尿苷在几种癌症的发生和发展中发挥着关键作用。以往的研究表明，假尿苷5‘-磷酸酶(PUDP)可能是一种新的结直肠癌预后生物标志物。然而，在过去，我们对PUDP的关注很少，对其在癌症中的功能和作用仍不清楚。在这项研究中，我们首先利用癌症基因组图谱(TCGA)和基因-组织表达(GTEx)数据对PUDP的表达和预后进行了泛癌分析，我们发现PUDP可能是一个潜在的肝癌癌基因。通过表达分析、相关性分析和生存分析，确定与PUDP有关的最有潜力的上游microRNA为let-7c-5p。随后，单细胞RNA测序(scRNA-seq)结果表明，PUDP在肿瘤细胞中显著高表达。此外，PUDP与肿瘤免疫细胞浸润、免疫细胞生物标志物、免疫检查点表达呈显著正相关，尤其与促肿瘤免疫细胞如T细胞调节细胞(Treg)、髓系抑制细胞(MDSC)、肿瘤相关成纤维细胞(CAF)呈正相关。此外，我们还发现三个基因座的甲基化水平与PUDP的表达呈正相关，四个基因座的甲基化水平与PUDP的表达呈负相关。对本中心收治的15对肝癌及癌旁正常组织进行了生物信息学分析，实验结果与生物信息学分析结果基本一致。我们的研究表明，PUDP高表达的肝癌患者从免疫治疗中获益的可能性较小，此外，我们还探讨了PUDP与抗癌药物的关系。最后，我们探讨了PUDP的临床相关性，将PUDP确定为肝癌患者的独立危险因素，并构建了预后模型，使用国际癌症基因组联合会(ICGC)的数据进行外部验证。总之，我们的研究表明，PUDP的高表达提示预后不良，对免疫治疗的反应性低，为了解肝癌的治疗和预后提供了新的视角。
Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world and is notorious for poor prognosis. There is mounting evidence that pseudouridine performs key functions in the initiation and progression of several cancers. A previous study demonstrated that Pseudouridine 5’-phosphatase (PUDP) may be a novel prognostic biomarker in colorectal cancer. However, in the past, we have paid little attention to PUDP and we are still not clear about its function and role in cancer. In this study, a pan-cancer analysis of PUDP expression and prognosis was performed firstly using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data and we found that PUDP may be a potential oncogene for HCC. Then the most potential upstream microRNA contributing to PUDP was identified as let-7c-5p through expression analysis, correlation analysis, and survival analysis. Subsequently, the result of single cell RNA sequencing (scRNA-seq) demonstrated that PUDP was significantly highly expressed on malignant cells. In addition, there are significantly positive correlations between PUDP and tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression, especially with tumor-promoting immune cells such as T cell regulatory (Treg), Myeloid-derived suppressor cell (MDSC), cancer-associated fibroblast (CAF). Moreover, we found the methylation level of three loci was positively correlated with PUDP expression and four loci were negatively correlated. 15 pairs of HCC and normal adjacent tissues from HCC patients who were treated at our center were used to verify the results of the bioinformatics analysis and the results of experiments are similar to the bioinformatics analysis. Our study demonstrated that HCC patients with high PUDP expression are less likely to benefit from immunotherapy, and in addition, we explored the relationship between PUDP and anticancer drugs. Finally, we explored the clinical relevance of PUDP, identified PUDP as an independent risk factor for HCC patients and constructed a prognostic model, used International Cancer Genome Consortium (ICGC) data to do external validation. Collectively, our study demonstrated that high expression of PUDP suggested a poor prognosis and low response to immunotherapy, providing new insight into the treatment and prognosis of HCC.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
starBase v2.0：从大规模 CLIP-Seq 数据中解码 miRNA-ceRNA、miRNA-ncRNA 和蛋白质-RNA 相互作用网络
影响因子：
14.9
作者：
Li JH;Liu S;Zhou H;Qu LH;Yang JH
通讯作者：
Yang JH
DOI：
10.1186/s13046-017-0496-2
发表时间：
2017-02-06
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Grünow J;Rong C;Hischmann J;Zaoui K;Flechtenmacher C;Weber KJ;Plinkert P;Hess J
通讯作者：
Hess J
影响因子：
13.5
作者：
Giannini, Edoardo G.;Farinati, Fabio;Trevisani, Franco
通讯作者：
Trevisani, Franco
影响因子：
4.4
作者：
Koch A;De Meyer T;Jeschke J;Van Criekinge W
通讯作者：
Van Criekinge W