Bioinformatics reveal elevated levels of Myosin Vb in uterine corpus endometrial carcinoma patients which correlates to increased cell metabolism and poor prognosis.
Bioinformatics reveal elevated levels of Myosin Vb in uterine corpus endometrial carcinoma patients which correlates to increased cell metabolism and poor prognosis.
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DOI：
10.1371/journal.pone.0280428
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Engevik, Amy C.
中科院分区：
文献类型：
--
作者：
Engevik, Kristen A.;Engevik, Melinda A.;Engevik, Amy C.
子宫内膜癌是最常见的女性盆腔恶性肿瘤。虽然子宫体子宫内膜癌（UCEC）如果早期切除的话预后良好，但肿瘤分期晚期的患者生存率较低。这些事实凸显了了解 UCEC 生物学的重要性。对 UCEC 患者 RNA 测序数据的计算分析显示，分子运动肌球蛋白 Vb (MYO5B) 在 UCEC 的早期阶段升高，并且发生在所有患者中，无论肿瘤分期、肿瘤类型、年龄、绝经状态或种族如何。尽管在 UCEC 患者的 MYO5B 基因中发现了一些突变，但这些突变与 mRNA 表达无关。 MYO5B 甲基化检查显示，UCEC 患者的 MYO5B 甲基化不足，且甲基化不足与 mRNA 和蛋白质水平增加呈正相关。免疫染色证实，与邻近组织相比，UCEC 患者的顶端 MYO5B 水平升高。正如生存曲线所反映的，具有高表达MYO5B肿瘤的UCEC患者的预后比具有低表达MYO5B肿瘤的UCEC患者差得多。代谢途径分析显示UCE患者代谢途径发生显着改变，关键代谢基因与MYO5B mRNA呈正相关。这些数据提供了MYO5B可能参与UCEC肿瘤发生的第一个证据。
Carcinoma of the endometrium of the uterus is the most common female pelvic malignancy. Although uterine corpus endometrial cancer (UCEC) has a favorable prognosis if removed early, patients with advanced tumor stages have a low survival rate. These facts highlight the importance of understanding UCEC biology. Computational analysis of RNA-sequencing data from UCEC patients revealed that the molecular motor Myosin Vb (MYO5B) was elevated in the beginning stages of UCEC and occurred in all patients regardless of tumor stage, tumor type, age, menopause status or ethnicity. Although several mutations were identified in the MYO5B gene in UCEC patients, these mutations did not correlate with mRNA expression. Examination of MYO5B methylation revealed that UCEC patients had undermethylated MYO5B and undermethylation was positively correlated with increased mRNA and protein levels. Immunostaining confirmed elevated levels of apical MYO5B in UCEC patients compared to adjacent tissue. UCEC patients with high expressing MYO5B tumors had far worse prognosis than UCEC patients with low expressing MYO5B tumors, as reflected by survival curves. Metabolic pathway analysis revealed significant alterations in metabolism pathways in UCE patients and key metabolism genes were positively correlated with MYO5B mRNA. These data provide the first evidence that MYO5B may participate in UCEC tumor development.
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