The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers
The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers
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Netrin家族的泛癌景观揭示了潜在的致癌生物标志物
DOI：
10.1038/s41598-020-62117-5
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发表时间：
2020-03-23
影响因子：
4.6
通讯作者：
Zhu, Yuyan
中科院分区：
文献类型：
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作者：
Hao, Wenjun;Yu, Meng;Zhu, Yuyan
最近的癌症研究发现，网状蛋白家族在某些癌症的发展中起着至关重要的作用。然而，这些蛋白质的许多变体在癌症中的功能仍然不完全清楚。在这项工作中，我们使用了最全面的数据库，包括30多种肿瘤类型的10000多个样本，来分析netrin家族的6个成员。我们对netrin基因的遗传变化和表达进行了综合分析，分析了netrin基因的表观遗传和通路关系，以及这些蛋白的表达与药物敏感性的相关性。虽然netrin家族在泛癌中的突变率较低，但在netrin突变的肿瘤患者中，以子宫体子宫内膜癌患者数量最多，占13.6%（397例中有54例）。有趣的是，netrin家族成员NTNG1的最高突变率为38%（397个中的152个）。Netrin蛋白可能参与内分泌相关肿瘤和性激素靶向器官肿瘤的发生发展。此外，NTNG1和NTNG2在各种癌症中的参与显示了它们作为新的肿瘤标志物和治疗靶点的潜力。这一分析为该蛋白家族提供了广阔的分子视角，并为癌症治疗提供了一些新的方向。
Recent cancer studies have found that the netrin family of proteins plays vital roles in the development of some cancers. However, the functions of the many variants of these proteins in cancer remain incompletely understood. In this work, we used the most comprehensive database available, including more than 10000 samples across more than 30 tumor types, to analyze the six members of the netrin family. We performed comprehensive analysis of genetic change and expression of the netrin genes and analyzed epigenetic and pathway relationships, as well as the correlation of expression of these proteins with drug sensitivity. Although the mutation rate of the netrin family is low in pan-cancer, among the tumor patients with netrin mutations, the highest number are Uterine Corpus Endometrial Carcinoma patients, accounting for 13.6% of cases (54 of 397). Interestingly, the highest mutation rate of a netrin family member is 38% for NTNG1 (152 of 397). Netrin proteins may participate in the development of endocrine-related tumors and sex hormone-targeting organ tumors. Additionally, the participation of NTNG1 and NTNG2 in various cancers shows their potential for use as new tumor markers and therapeutic targets. This analysis provides a broad molecular perspective of this protein family and suggests some new directions for the treatment of cancer.