Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling.
Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling.
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DOI：
10.3390/cancers13040794
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发表时间：
2021-02-14
期刊：
影响因子：
5.2
通讯作者：
Hardisson D
中科院分区：
文献类型：
--
作者：
López-Janeiro Á;Ruz-Caracuel I;Ramón-Patino JL;De Los Ríos V;Villalba Esparza M;Berjón A;Yébenes L;Hernández A;Masetto I;Kadioglu E;Goubert V;Heredia-Soto V;Barderas R;Casal JI;de Andrea CE;Redondo A;Mendiola M;Peláez-García A;Hardisson D
低度、早期子宫内膜癌（EC）是子宫体最常见的恶性肿瘤。我们的研究旨在通过蛋白质组学分析来评估这一特定EC亚群中的失调途径。我们描述并验证了SLIT/ROBO信号通路的失调，以及细胞死亡过程，如坏死性凋亡和铁凋亡。我们确定了几个免疫相关的途径，先天免疫反应相关的途径占主导地位。我们的研究结果揭示了低级，早期EC的独特生物学，并可以指导该领域的未来研究。低级别、早期子宫内膜癌（EC）是子宫体最常见的恶性肿瘤。然而，这些肿瘤背后的分子改变远未完全理解。本研究的目的是描述从EC患者失调的分子途径。收集16个肿瘤组织和配对的健康对照样品，并对两者进行质谱（MS）/MS蛋白质组学分析。使用不同的数据库和生物信息学工具进行基因本体和途径分析以发现失调的途径和/或蛋白质。在一个独立的外部队列中交叉验证了失调途径。细胞信号传导、免疫应答和细胞死亡相关途径得到了有力鉴定。SLIT/ROBO信号通路在蛋白质组和转录组水平上表现出失调。除了细胞凋亡外，坏死性凋亡和铁凋亡是细胞死亡相关的异常调节过程。免疫应答相关途径显示先天免疫应答占主导地位。通过免疫荧光测量的肿瘤免疫浸润显示了不同的淋巴和骨髓群体。我们的研究结果表明SLIT/ROBO，坏死性凋亡和铁凋亡的作用，以及先天免疫反应在低级，早期EC中的突出作用。这些结果可以指导这组肿瘤的未来研究。
Low-grade, early-stage endometrial cancer (EC) is the most frequent malignant tumor of the uterine corpus. Our study aimed to assess dysregulated pathways in this specific subset of EC through proteomic analysis. We describe and validate the dysregulation of the SLIT/ROBO signaling pathway, as well as cellular death processes such as necroptosis and ferroptosis. We identify several immune-related pathways, with a dominance of innate immune response associated pathways. Our findings reveal the singular biology of low-grade, early-stage ECs and could guide future research in the field. Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
8.4
作者：
Jeppesen, Mette Moustgaard;Jensen, Pernille Tine;Mogensen, Ole
通讯作者：
Mogensen, Ole
DOI：
10.1093/bioinformatics/btp101
发表时间：
2009-04-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Bindea G;Mlecnik B;Hackl H;Charoentong P;Tosolini M;Kirilovsky A;Fridman WH;Pagès F;Trajanoski Z;Galon J
通讯作者：
Galon J
影响因子：
64.8
作者：
Biankin, Andrew V.;Waddell, Nicola;Kassahn, Karin S.;Gingras, Marie-Claude;Muthuswamy, Lakshmi B.;Johns, Amber L.;Miller, David K.;Wilson, Peter J.;Patch, Ann-Marie;Wu, Jianmin;Chang, David K.;Cowley, Mark J.;Gardiner, Brooke B.;Song, Sarah;Harliwong, Ivon;Idrisoglu, Senel;Nourse, Craig;Nourbakhsh, Ehsan;Manning, Suzanne;Wani, Shivangi;Gongora, Milena;Pajic, Marina;Scarlett, Christopher J.;Gill, Anthony J.;Pinho, Andreia V.;Rooman, Ilse;Anderson, Matthew;Holmes, Oliver;Leonard, Conrad;Taylor, Darrin;Wood, Scott;Xu, Qinying;Nones, Katia;Fink, J. Lynn;Christ, Angelika;Bruxner, Tim;Cloonan, Nicole;Kolle, Gabriel;Newell, Felicity;Pinese, Mark;Mead, R. Scott;Humphris, Jeremy L.;Kaplan, Warren;Jones, Marc D.;Colvin, Emily K.;Nagrial, Adnan M.;Humphrey, Emily S.;Chou, Angela;Chin, Venessa T.;Chantrill, Lorraine A.;Mawson, Amanda;Samra, Jaswinder S.;Kench, James G.;Lovell, Jessica A.;Daly, Roger J.;Merrett, Neil D.;Toon, Christopher;Epari, Krishna;Nguyen, Nam Q.;Barbour, Andrew;Zeps, Nikolajs;Kakkar, Nipun;Zhao, Fengmei;Wu, Yuan Qing;Wang, Min;Muzny, Donna M.;Fisher, William E.;Brunicardi, F. Charles;Hodges, Sally E.;Reid, Jeffrey G.;Drummond, Jennifer;Chang, Kyle;Han, Yi;Lewis, Lora R.;Dinh, Huyen;Buhay, Christian J.;Beck, Timothy;Timms, Lee;Sam, Michelle;Begley, Kimberly;Brown, Andrew;Pai, Deepa;Panchal, Ami;Buchner, Nicholas;De Borja, Richard;Denroche, Robert E.;Yung, Christina K.;Serra, Stefano;Onetto, Nicole;Mukhopadhyay, Debabrata;Tsao, Ming-Sound;Shaw, Patricia A.;Petersen, Gloria M.;Gallinger, Steven;Hruban, Ralph H.;Maitra, Anirban;Iacobuzio-Donahue, Christine A.;Schulick, Richard D.;Wolfgang, Christopher L.;Morgan, Richard A.;Lawlor, Rita T.;Capelli, Paola;Corbo, Vincenzo;Scardoni, Maria;Tortora, Giampaolo;Tempero, Margaret A.;Mann, Karen M.;Jenkins, Nancy A.;Perez-Mancera, Pedro A.;Adams, David J.;Largaespada, David A.;Wessels, Lodewyk F. A.;Rust, Alistair G.;Stein, Lincoln D.;Tuveson, David A.;Copeland, Neal G.;Musgrove, Elizabeth A.;Scarpa, Aldo;Eshleman, James R.;Hudson, Thomas J.;Sutherland, Robert L.;Wheeler, David A.;Pearson, John V.;McPherson, John D.;Gibbs, Richard A.;Grimmond, Sean M.
通讯作者：
Grimmond, Sean M.
DOI：
10.1038/s41379-018-0080-0
发表时间：
2018-10
期刊：
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
影响因子：
--
作者：
Kim G;Kurnit KC;Djordjevic B;Singh C;Munsell MF;Wang WL;Lazar AJ;Zhang W;Broaddus R
通讯作者：
Broaddus R