The DNA damage repair-related gene PKMYT1 is a potential biomarker in various malignancies.

The DNA damage repair-related gene PKMYT1 is a potential biomarker in various malignancies.
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DNA损伤修复相关基因PKMYT1是多种恶性肿瘤的潜在生物标志物

DOI:
10.21037/tlcr-21-973
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发表时间:
2021-12
影响因子:
4
通讯作者:
Yan X
Yan X
中科院分区:
医学3区
文献类型:
--
作者:
Shao C;Wang Y;Pan M;Guo K;Molnar TF;Kocher F;Seeber A;Barr MP;Navarro A;Han J;Ma Z;Yan X

文献摘要

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背景 蛋白激酶膜相关酪氨酸/苏氨酸 1 (PKMYT1) 调节细胞周期,是 DNA 损伤修复 (DDR) 相关信号传导的一部分。最近的研究已经确定 PKMYT1 在肿瘤免疫和 DDR 中的作用。因此,我们发起了这项研究,旨在表征癌症中 PKMYT1 的分子和免疫学特征。方法 使用从基因型组织表达 (GTEx)、癌症基因组图谱 (TCGA) 和癌细胞系百科全书 (CCLE) 数据集推断的转录组数据来确定 PKMYT1 的 mRNA 表达水平。 PKMYT1 mRNA 表达状态与患者的预后以及 34 种不同肿瘤中的免疫新抗原和免疫检查点相关。肿瘤免疫估计资源(TIMER)数据集用于分析免疫浸润评分。结果 PKMYT1 mRNA 在常见肿瘤中存在差异表达,除恶性胸腺瘤(THYM)外,PKMYT1 mRNA 高表达与预后不良相关。此外,PKMYT1 mRNA 表达与肿瘤浸润免疫细胞相关,特别是在肺鳞状细胞癌、食管癌、THYM 和肺腺癌中。在 PKMYT1 mRNA 高表达的肿瘤中观察到免疫检查点和新抗原的上调。基因集富集分析 (GSEA) 的数据显示 PKMYT1 参与肿瘤免疫原性、代谢和细胞周期进展。结论 PKMYT1在多种癌症中差异表达,对肿瘤免疫和进展发挥重要作用。 PKMYT1 基因具有作为新的潜在生物标志物的潜力。因此,显然需要进一步的研究来阐述我们的发现。
Background Protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) regulates cell cycle and is a part of DNA damage repair (DDR)-related signaling. Recent studies have identified a role for PKMYT1 in tumor immunity and DDR. Thus, we initiated this study aiming to characterize the molecular and immunological portrait of PKMYT1 in cancer. Methods Transcriptomic data extrapolated from Genotype-Tissue Expression (GTEx), The Cancer Genome Atlas (TCGA), and Cancer Cell Line Encyclopedia (CCLE) datasets were used to determine the mRNA expression levels of PKMYT1. PKMYT1 mRNA expression status was correlated with patients’ prognosis as well as immune neoantigens, and immune checkpoints in 34 different tumors. The Tumor Immune Estimation Resource (TIMER) dataset was used to analyze immune infiltrating scores. Results PKMYT1 mRNA is differentially expressed in common tumors and high expression levels of PKMYT1 mRNA is associated with poor prognosis except for malignant thymoma (THYM). In addition, PKMYT1 mRNA expression was correlated with tumor-infiltrating immune cells particularly in lung squamous cell carcinoma, esophageal carcinoma, THYM, and lung adenocarcinoma. An upregulation of immune checkpoints and neoantigens was observed in tumors with a high PKMYT1 mRNA expression. Data from gene set enrichment analysis (GSEA) revealed that PKMYT1 is involved in tumor immunogenicity, metabolism, and cell cycle progression. Conclusions PKMYT1 is differentially expressed in various cancers and exerts an important effect on tumor immunity and progression. The PKMYT1 gene holds the potential as a new potential biomarker. Therefore, further studies are clearly needed to elaborate our findings.