Defining the human kidney N‐glycome in normal and cancer tissues using MALDI imaging mass spectrometry

Drake Richard R.; McDowell Colin; West Connor; David Fred; Powers Thomas W.; Nowling Tamara; Bruner Evelyn; Mehta Anand S.; Angel Peggi M.; Marlow Laura A.; Tun Han W.; Copland John A.

摘要

Abstract >Clear‐cell renal cell carcinoma (ccRCC) presents challenges to clinical management because of late‐stage detection, treatment resistance, and frequent disease recurrence. Metabolically, ccRCC has a well‐described Warburg effect utilization of glucose, but how this affects complex carbohydrate synthesis and alterations to protein and cell surface glycosylation is poorly defined. Using an imaging mass spectrometry approach, N‐glycosylation patterns and compositional differences were assessed between tumor and nontumor regions of formalin‐fixed clinical ccRCC specimens and tissue microarrays. Regions of normal kidney tissue samples were also evaluated for N‐linked glycan‐based distinctions between cortex, medullar, glomeruli, and proximal tubule features. Most notable was the proximal tubule localized detection of abundant multiantennary N‐glycans with bisecting N‐acetylglucosamine and multziple fucose residues. These glycans are absent in ccRCC tissues, while multiple tumor‐specific N‐glycans were detected with tri‐ and tetra‐antennary structures and varying levels of fucosylation and sialylation. A polycystic kidney disease tissue was also characterized for N‐glycan composition, with specific nonfucosylated glycans detected in the cyst fluid regions. Complementary to the imaging mass spectrometry analyses was an assessment of transcriptomic gene array data focused on the fucosyltransferase gene family and other glycosyltransferase genes. The transcript levels of the FUT3 and FUT6 genes responsible for the enzymes that add fucose to N‐glycan antennae were significantly decreased in all ccRCC tissues relative to matching nontumor tissues. These striking differences in glycosylation associated with ccRCC could lead to new mechanistic insight into the glycobiology underpinning kidney malignancies and suggest the potential for new therapeutic interventions and diagnostic markers. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译：</span><Abstract Type =“Main”XML：Lang =“en”> <标题类型=“main”>抽象</ title> >透明细胞肾细胞癌（CCRCC）由于晚期的检测，治疗抵抗和频繁的疾病复发，对临床管理提出挑战。代谢地，CCRCC具有良好描述的Warburg效应利用葡萄糖，但这将如何影响复杂的碳水化合物合成和对蛋白质和细胞表面糖基化的改变定义。使用成像质谱法，在福尔马林固定的临床CCRCC标本和组织微阵列的肿瘤和不瘤区域之间评估了N-糖基化模式和组成差异。还评估了正常的肾组织样品的区域，用于在皮质，髓质，肾小球和近端小管间之间的N-连接的基于Glycan的区别。最值得注意的是具有分化N-乙酰葡糖胺和荧光葡萄糖残基的近端小管局部检测丰富的多银N-聚糖。这些聚糖在CCRCC组织中不存在，而使用三长年节结构和不同水平的岩藻糖基化和唾液酸化物检测多种肿瘤特异性N-聚糖。多囊肾疾病组织还表征了N-聚糖组合物，其中在囊肿流体区域中检测到特异的非氟糖基化聚糖。对成像质谱分析的互补是对聚焦的转录组基因阵列数据的评估，其聚焦在岩藻糖基转移酶基因家族和其他糖基转移酶基因上。在所有CCRCC组织中相对于匹配的Nontumor组织，所有CCRCC组织的酶负责的Fut3和Fut6基因的转录水平显着降低。这些与CCRCC相关的糖基化的突出差异可能导致新的机制洞察力识别糖尿病，内因肾病恶性肿瘤，并表明新治疗干预和诊断标志物的潜力。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-34906/'>《Journal of mass spectrometry: JMS》</a> <b style="margin: 0 2px;">|</b><span>2020年第4期</span><b style="margin: 0 2px;">|</b><span>共10页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Drake Richard R.&option=202" target="_blank" rel="nofollow">Drake Richard R.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=McDowell Colin&option=202" target="_blank" rel="nofollow">McDowell Colin;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=West Connor&option=202" target="_blank" rel="nofollow">West Connor;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=David Fred&option=202" target="_blank" rel="nofollow">David Fred;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Powers Thomas W.&option=202" target="_blank" rel="nofollow">Powers Thomas W.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Nowling Tamara&option=202" target="_blank" rel="nofollow">Nowling Tamara;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bruner Evelyn&option=202" target="_blank" rel="nofollow">Bruner Evelyn;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Mehta Anand S.&option=202" target="_blank" rel="nofollow">Mehta Anand S.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Angel Peggi M.&option=202" target="_blank" rel="nofollow">Angel Peggi M.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Marlow Laura A.&option=202" target="_blank" rel="nofollow">Marlow Laura A.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Tun Han W.&option=202" target="_blank" rel="nofollow">Tun Han W.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Copland John A.&option=202" target="_blank" rel="nofollow">Copland John A.;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Medicine Division of Rheumatology and ImmunologyMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Pathology and Laboratory MedicineMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cell and Molecular Pharmacology and Experimental TherapeuticsMedical University of South CarolinaCharleston SC 29425 USA;</p> <p>Department of Cancer BiologyMayo ClinicJacksonville FL 32224 USA;</p> <p>Department of Cancer BiologyMayo ClinicJacksonville FL 32224 USA;</p> <p>Department of Cancer BiologyMayo ClinicJacksonville FL 32224 USA;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/1187.html" title="分析化学">分析化学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=clear‐cell renal cell carcinoma&option=203" rel="nofollow">clear‐cell renal cell carcinoma;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=fucosylation&option=203" rel="nofollow">fucosylation;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=MALDI imaging&option=203" rel="nofollow">MALDI imaging;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=N‐glycosylation&option=203" rel="nofollow">N‐glycosylation;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=polycystic kidney disease&option=203" rel="nofollow">polycystic kidney disease;</a> </p> <div class="translation"> 机译：透明细胞肾细胞癌;岩氧化;马尔迪成像;n-糖基化;多囊肾病; </div> </li> </ul> </div> </div> <div class="literature cardcommon" id="literaturereference" style="display:none"> <div class="similarity "> <h3 class="all_title" id="enpatent111">引文网络</h3> <div class="referencetab clearfix"> <ul id="referencedaohang"> <li dataid="referenceul">参考文献</li> <li dataid="citationul">引证文献</li> <li dataid="commonreferenceul">共引文献</li> <li dataid="commoncitationul">同被引文献</li> <li dataid="tworeferenceul">二级参考文献</li> <li dataid="twocitationul">二级引证文献</li> </ul> </div> <div class="reference_details" id="referenceList"> <ul id="referenceul"></ul> <ul id="citationul"></ul> <ul id="commonreferenceul"></ul> <ul id="commoncitationul"></ul> <ul id="tworeferenceul"></ul> <ul id="twocitationul"></ul> </div> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab 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Lin,</a> <span>2019</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：质谱成像使得能够从肾细胞癌亚型和正常肾组织中的肾儿肾细胞瘤歧视</span> </p> </li> <li> <div> <b>8. </b><a class="enjiyixqcontent" href="/ntis-science-report_ad_thesis/02071100399.html">MALDI/Mass Spectrometry of 'Normal Appearing' and Dystrophic Axons in Spinal Cord of Multiple Sclerosis (MS).</a> <b>[R] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Iram, S.&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Iram, S. </a> <span>2013</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：多发性硬化（ms）脊髓中“正常出现”和营养不良轴突的maLDI /质谱分析。</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a 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href="/academic-journal-cn_chinese-journal-pathophysiology_thesis/0201292190604.html">用MALDI成像质谱法观察β-淀粉样肽类在阿尔茨海默病脑中的差异性沉积</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=张贺平&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 张贺平</a> <span> <a href="/journal-cn-5784/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中国病理生理杂志 </a> </span> <span> . 2018</span><span>,第2期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_journal-zhengzhou-university-medical-sciences_thesis/0201245379079.html">不同离体时间人卵巢癌组织在正常小鼠肾包膜下生长规律的探讨</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王建六&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 王建六</a> <span> <a href="/journal-cn-6518/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 郑州大学学报（医学版） </a> </span> <span> . 1997</span><span>,第004期</span> </span> </div> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/academic-journal-cn_journal-chinese-mass-spectrometry-society_thesis/0201226256393.html">基体辅助激光解吸质谱法(MALDI-MS)在生物化学中的应用</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=赵善楷&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 赵善楷</a> <span> <a href="/journal-cn-8285/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 质谱学报 </a> </span> <span> . 1996</span><span>,第002期</span> </span> </div> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/academic-journal-cn_zhejiang-medical-journal_thesis/0201255037011.html">联用2-DE和MALDI-TOF-MS技术筛查胃癌组织和血清中的差异蛋白质</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=夏英捷&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 夏英捷</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=马英玉&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,马英玉</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王惠菊&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,王惠菊</a> <span> <a href="/journal-cn-6716/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 浙江医学 </a> </span> <span> . 2010</span><span>,第009期</span> </span> </div> </li> <li> <div> <b>6. </b><a class="enjiyixqcontent" href="/academic-conference-cn_meeting-5990_thesis/020221527290.html">使用心脏宝石能谱成像技术进行正常人心外膜脂肪容积定量</a> <b>[C]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=张璋&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 张璋</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=苏大同&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,苏大同</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=李菲&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,李菲</a> <span> <a href="/conference-cn-5990/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 中华医学会第十五次全国心血管病学大会 </a> <span> <span> . 2013</span> </span> </div> </li> <li> <div> <b>7. </b><a class="enjiyixqcontent" href="/academic-degree-domestic_mphd_thesis/02031124772.html">TFAR19（PDCD5）蛋白在正常肾、肾透明细胞癌组织及正常膀胱、膀胱癌组织中的表达及意义</a> <b>[A] </b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=熊林&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 熊林</a> <span> . 2006</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06120104193568.html">MALDI质谱法用水不溶性物质的试验片的制备方法和使用MALDI质谱法定量分析水不溶性物质的方法</a> <b>[P]</b> . <span> 中国专利： CN111527391A </span> <span> . 2020-08-11</span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06120101496120.html">使用MALDI质谱法定量分析聚合物的方法，和制备用于定量分析聚合物的MALDI质谱法的试样的方法</a> <b>[P]</b> . <span> 中国专利： CN110612441A </span> <span> . 2019-12-24</span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130402404195.html">MALDI mass spectrometry measurement sample preparation method, MALDI mass spectrometry measurement sample preparation device, MALDI mass spectrometry measurement sample, MALDI mass spectrometry method, and MALDI mass spectrometry measurement sample preparation program</a> <b>[P]</b> . <span> 外国专利：  JP2020160046A </span> <span> . 2020-10-01</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：MALDI质谱测量样品制备方法，MALDI质谱测量样品制备装置，MALDI质谱测量样品，MALDI质谱方法和MALDI质谱测量样品制备程序 </span> </p> </li> <li> <div> <b>4. </b><a class="enjiyixqcontent" href="/patent-detail/06130500492107.html">Method and device for preparing measurement sample for MALDI mass spectrometry, measurement sample for MALDI mass spectrometry, MALDI mass spectrometry method, and non-transitory recording medium for preparing measurement sample for MALDI mass spectrometry</a> <b>[P]</b> . <span> 外国专利：  US11094517B2 </span> <span> . 2021-08-17</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：用于制备MALDI质谱法的测量样品的方法和装置，用于MALDI质谱法，MALDI质谱法和非暂时记录介质的测量样品，用于制备MALDI质谱法的测量样品 </span> </p> </li> <li> <div> <b>5. </b><a class="enjiyixqcontent" href="/patent-detail/06130401637713.html">METHOD AND DEVICE FOR PREPARING MEASUREMENT SAMPLE FOR MALDI MASS SPECTROMETRY, MEASUREMENT SAMPLE FOR MALDI MASS SPECTROMETRY, MALDI MASS SPECTROMETRY METHOD, AND NON-TRANSITORY RECORDING MEDIUM FOR PREPARING MEASUREMENT SAMPLE FOR MALDI MASS SPECTROMETRY</a> <b>[P]</b> . <span> 外国专利：  US2020303176A1 </span> <span> . 2020-09-24</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译：制备马尔代质谱的测量样品的方法和装置，马尔代质谱的测量样品，马尔代质谱的方法以及制备马尔代质谱的测量样品的非暂态记录介质 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" class="downloadBth" style="bottom: 19px;z-index: 999;" onclick="ywcd('0704025633067','4',7,2,1,'',this,24)" class="delivery" prompt="010401" title="通过人工服务将文献原文发送至邮箱" >获取原文</div> <div class="journalsub-pop-up" style="display: none"> <div class="journal-sub"> <h2>期刊订阅</h2> <img src="https://cdn.zhangqiaokeyan.com/img/loginclose.png" alt="关闭" 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