PUM1 is upregulated by DNA methylation to suppress antitumor immunity and results in poor prognosis in pancreatic cancer.
PUM1 is upregulated by DNA methylation to suppress antitumor immunity and results in poor prognosis in pancreatic cancer.
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PUM1 通过 DNA 甲基化上调，抑制抗肿瘤免疫，导致胰腺癌预后不良
DOI：
10.21037/tcr-20-3295
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发表时间：
2021-05
影响因子：
0.9
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Yang Y;Su X;Shen K;Zhang C;Dai H;Ma H;Jiang Y;Shuai L;Liu Z;You J;Min K;Chen Z
背景胰腺癌(PAAD)是一种恶性程度高、预后差、死亡率高的肿瘤。PUM1在非小细胞肺癌(NSCLC)、卵巢癌和淋巴细胞白血病等多种肿瘤中具有促进细胞生长、侵袭和转移、抑制细胞凋亡等作用。然而，PUM1在PAAD中的潜在机制和潜在作用尚未被研究。方法利用多种数据库[癌症基因组图谱(TCGA)、基因表达谱交互分析(GEPIA)、BBoma、人类蛋白质图谱(HPA)、MethSurv、cBioPortal、癌症影像档案(TCIA)、Xcell、基因表达总表(GEO)]进行生物信息学分析，探讨PUM1在PAAD患者中的诊断和预后作用，以及PUM1表达与预后的关系。使用Kaplan-Meier绘图仪进一步验证了这一分析。结果PUM1具有诊断和预测预后的作用。PUM1mRNA的表达水平与胰腺癌的预后和发病率密切相关。PUM1可作为胰腺癌的潜在诊断指标。此外，PUM1的DNA甲基化水平影响其在胰腺癌中的癌基因功能。PUM1还可通过改变免疫细胞的浸润抑制免疫微环境，从而影响胰腺癌的免疫治疗反应。结论PUM1在PAAD的免疫微环境和免疫治疗反应中起重要作用，可能有助于开发新的诊断和治疗策略。
Background Pancreatic carcinoma (PAAD) is a highly malignant cancer with a poor prognosis and high mortality rate. Pumilio homologous protein 1 (PUM1) promotes cell growth, invasion, and metastasis and suppresses apoptosis in many different kinds of cancers, such as non-small-cell lung carcinoma (NSCLC), ovarian cancer and lymphocyte leukemia. However, the underlying mechanism and potential role of PUM1 in PAAD have not been investigated. Methods Bioinformatics analysis was performed using multiple databases [The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), BBCancer, Human Protein Atlas (HPA), MethSurv, cBioPortal, The Cancer Imaging Archive (TCIA), xCell, Gene Expression Omnibus (GEO)] to explore the diagnostic and prognostic role of PUM1, and the relationship between expression of PUM1 and prognosis of patients with PAAD. The analysis was further validated using the Kaplan-Meier plotter. Results PUM1 plays a role in both diagnostic and prognostic prediction. The PUM1 mRNA expression level correlates with both the prognosis and incidence of pancreatic cancer. PUM1 can serve as a potential diagnostic indicator for pancreatic cancer. Furthermore, the DNA methylation levels of PUM1 affects its oncogene function in pancreatic cancer. PUM1 can also inhibit the immune microenvironment by altering immune cell infiltration, which affects immunotherapy response in pancreatic cancer. Conclusions PUM1 takes a crucial part in the immune microenvironment and immunotherapy response of PAAD and is potentially useful for the development of novel diagnostic and treatment strategies.