Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients.
Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients.
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DOI：
10.1038/s41598-021-88585-x
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发表时间：
2021-04-30
影响因子：
4.6
通讯作者：
Larry Maxwell G
中科院分区：
文献类型：
--
作者：
Bateman NW;Tarney CM;Abulez T;Soltis AR;Zhou M;Conrads K;Litzi T;Oliver J;Hood B;Driggers P;Viollet C;Dalgard C;Wilkerson M;Catherino W;Hamilton CA;Darcy KM;Casablanca Y;Al-Hendy A;Segars J;Conrads TP;Larry Maxwell G
富马酸水合酶（FH）的致病性突变驱动遗传性平滑肌瘤病和肾细胞癌（HLRCC），并增加发生子宫平滑肌瘤（ULM）的风险。来自HLRCC（n = 16; FH突变证实）和非综合征（NS）患者（n = 12）的ULM的整合蛋白基因组学分析鉴定出HLRCC（R = 0.35）与NS ULM（R = 0.242，MWU p = 0.0015）中显著更高的蛋白质：转录本相关性。共改变的蛋白质和转录物（228）包括抗氧化反应元件（ARE）靶基因，如硫氧还蛋白还原酶1（TXNRD 1），并与HLRCC ULM中NRF 2介导的氧化应激反应信号传导的激活相关。我们确认了185个先前描述的在HLRCC和NS ULM之间改变的转录物，51个在蛋白质水平上共同改变的转录物和几个在HLRCC ULM中升高的转录物参与调节细胞代谢和糖酵解信号传导。此外，在HLRCC ULM中鉴定了367个S-（2-琥珀酰基）半胱氨酸肽，其中60个在HLRCC中相对于NS ULM显著升高（LogFC = 1.86，MWU p < 0.0001）。这些结果证实并定义了从HLRCC患者收集的子宫平滑肌瘤组织中新的蛋白基因组学改变，并强调了与FH肿瘤抑制基因失活相关的保守分子改变。
Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs. NS ULMs (R = 0.242, MWU p = 0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC = 1.86, MWU p < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.
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DOI：
10.1073/pnas.1518752113
发表时间：
2016-02-02
影响因子：
11.1
作者：
Mehine, Miika;Kaasinen, Eevi;Aaltonen, Lauri A.
通讯作者：
Aaltonen, Lauri A.
影响因子：
64.5
作者：
Gillette, Michael A.;Satpathy, Shankha;Carr, Steven A.
通讯作者：
Carr, Steven A.
影响因子：
5.3
作者：
Kerins, Michael John;Vashisht, Ajay Amar;Ooia, Aikseng
通讯作者：
Ooia, Aikseng
影响因子：
4.4
作者：
Boettcher M;Lawson A;Ladenburger V;Fredebohm J;Wolf J;Hoheisel JD;Frezza C;Shlomi T
通讯作者：
Shlomi T
影响因子：
14.9
作者：
Metsalu T;Vilo J
通讯作者：
Vilo J