Extracellular matrix alterations in low‐grade lung adenocarcinoma compared with normal lung tissue by imaging mass spectrometry

Angel Peggi M.; Bruner Evelyn; Bethard Jennifer; Clift Cassandra L.; Ball Lauren; Drake Richard R.; Feghali‐Bostwick Carol

摘要

Abstract > Lung adenocarcinoma (LUAD) is the second most common cancer, affecting both men and women. Fibrosis is a hallmark of LUAD occurring throughout progression with excess production of extracellular matrix (ECM) components that lead to metastatic cell processes. Understanding the ECM cues that drive LUAD progression has been limited due to a lack of tools that can access and report on ECM components within the complex tumor microenvironment. Here, we test whether low‐grade LUAD can be distinguished from normal lung tissue using a novel ECM imaging mass spectrometry (ECM IMS) approach. ECM IMS analysis of a tissue microarray with 20 low‐grade LUAD tissues and 20 normal lung samples from 10 patients revealed 25 peptides that could discriminate between normal and low‐grade LUAD using area under the receiver‐operating curve (AUC) ≥0.7, P value ≤.001. Principal component analysis demonstrated that 62.4% of the variance could be explained by sample origin from normal or low‐grade tumor tissue. Additional work performed on a wedge resection with moderately differentiated LUAD demonstrated that the ECM IMS analytical approach could distinguish LUAD spectral features from spectral features of normal adjacent lung tissue. Conventional liquid chromatography with tandem mass spectrometry (LC‐MS/MS) proteomics demonstrated that specific sites of hydroxylation of proline (HYP) were a main collagen post translational modification that was readily detected in LUAD. A distinct peptide from collagen 3A1 modified by HYP was increased 3.5 fold in low‐grade LUAD compared with normal lung tissue (AUC 0.914, P value .001). This suggests that regulation of collagen proline hydroxylation could be an important process during early LUAD fibrotic deposition. ECM IMS is a useful tool that may be used to define fibrotic deposition in low‐grade LUAD. </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> > 肺腺癌（路加）是第二次常见的癌症，影响男女。纤维化是管道的标志，在整个进展中发生，具有过量生产的细胞外基质（ECM）组分导致转移细胞过程。由于缺乏可以访问和报告复杂肿瘤微环境中的ECM组分，因此了解驱动路障进展的ECM提示。在这里，我们测试是否可以使用新的ECM成像质谱（ECM IMS）方法与正常肺组织区分开低级路障。 ECM IMS分析具有20名低级管道组织的组织微阵列和来自10名患者的20例正常肺样品，揭示了25种肽，可以在接收器操作曲线（AUC）≥0.7下的区域下使用面积区分正常和低级拉德之间， p </ i> 值≤001。主成分分析证明，62.4％的差异可以通过来自正常或低级肿瘤组织的样品来解释。对具有中等区别的路德的楔形切除进行了额外的工作，表明ECM IMS分析方法可以区分从正常相邻肺组织的光谱特征的路障谱特征。常规液相色谱法与串联质谱（LC-MS / MS）蛋白质组学表现出来，脯氨酸羟基化的特异性位点（吡啶）是在路加易于检测的主要胶原转化改性后的主要胶原蛋白。与正常肺组织相比，由HYP改性的胶原蛋白3A1的不同肽增加3.5倍，低级拉兰折叠（AUC 0.914， p </ i> 值＆ .001）。这表明胶原蛋白脯氨酸羟基化的调节可能是在Luad纤维化沉积早期的重要过程。 ECM IMS是一种有用的工具，可用于在低级拉德中定义纤维化沉积。 </ 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11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=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=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=Bethard Jennifer&option=202" target="_blank" rel="nofollow">Bethard Jennifer;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Clift Cassandra L.&option=202" target="_blank" rel="nofollow">Clift Cassandra L.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ball Lauren&option=202" target="_blank" rel="nofollow">Ball Lauren;</a> <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=Feghali‐Bostwick Carol&option=202" target="_blank" rel="nofollow">Feghali‐Bostwick Carol;</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 &</p> <p>Experimental Therapeutics Proteomics CenterMedical University of South CarolinaCharleston South Carolina;</p> <p>Department of Pathology and Laboratory MedicineMedical University of South CarolinaCharleston South Carolina;</p> <p>Department of Cell and Molecular Pharmacology &</p> <p>Experimental Therapeutics Proteomics CenterMedical University of South CarolinaCharleston South Carolina;</p> <p>Department of Cell and Molecular Pharmacology &</p> <p>Experimental Therapeutics Proteomics CenterMedical University of South CarolinaCharleston South Carolina;</p> <p>Department of Cell and Molecular Pharmacology &</p> <p>Experimental Therapeutics Proteomics CenterMedical University of South CarolinaCharleston South Carolina;</p> <p>Department of Cell and Molecular Pharmacology &</p> <p>Experimental Therapeutics Proteomics CenterMedical University of South CarolinaCharleston South Carolina;</p> <p>Department of MedicineMedical University of South CarolinaCharleston South Carolina;</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=adenocarcinoma&option=203" rel="nofollow">adenocarcinoma;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=collagen&option=203" rel="nofollow">collagen;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=extracellular matrix&option=203" rel="nofollow">extracellular matrix;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=formalin‐fixed&option=203" rel="nofollow">formalin‐fixed;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=paraffin‐embedded tissue imaging&option=203" rel="nofollow">paraffin‐embedded tissue imaging;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=imaging mass spectrometry&option=203" rel="nofollow">imaging mass spectrometry;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=lung cancer&option=203" rel="nofollow">lung cancer;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=MALDI imaging mass spectrometry&option=203" rel="nofollow">MALDI imaging mass spectrometry;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=peptide imaging&option=203" rel="nofollow">peptide imaging;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=proteomics&option=203" rel="nofollow">proteomics;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=tissue imaging&option=203" rel="nofollow">tissue imaging;</a> </p> <div class="translation"> 机译：腺癌;胶原蛋白;细胞外基质;福尔马林固定;石蜡嵌入式组织成像;成像质谱;肺癌;马尔迪成像质谱;肽成像;蛋白质组学;组织成像; </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 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Szulik,</a> <span>2016</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：高血压患者的根直径和主动脉反转和正常主动脉的动脉高压患者右心室反散射信号强度的正常主动脉强度评估，作为测量严重肺病患者患者肌动脉高压肌动脉高压肌动脉高血压菌菌菌菌变化的方法。肺动脉高压患者患者患者群中左心室射血分数：临床和超声心动图特征P1111811潜临床左心室收缩功能障碍使用散斑跟踪超声心动图1012121221212121212121212121212121212121212121212121212121212121212121121212121212121111111111111111111111111111111111111111111111111111121212121212121211为本的适用于两种：在儿科心脏外科肺超声中妊娠期妊娠期间的形态学和功能适应：初步体验P1015Asymptomatic延迟编右心室穿孔通过心脏植入式电子设备导致，超声心动图featuresP1016Novel超声心动图预后标志物，从而在患者心脏压塞与大恶性心包积液。从流动到组织imagingP1017Doppler超声心动图参数模式转变为心脏tamponadeP1018Sigmoid隔膜的标志物所造成的atherosclerosisP1019Carotid动脉粥样硬化和刚度的进展胸主动脉的伸长率的标志物：在患者三重成像血管扩张应力回波的不同代谢measuresP1020Feasibility的比较疑似冠状动脉疾病P11022在成功的原发性经皮干预后患者的呼吸困难超声心动图和非罪魁祸首后的患者应激超声心动图患者患者的患者中患者中的患者歧视患者歧视心脏病患者的歧视和心动肺胁迫。患者中的应激超声心动图和非罪魁祸首P11024diaaltolic运动压力回声的不完全血运2型糖尿病患者中的露起舒张功能障碍，五年后续研究1025Dabetes Mellitus是SemiSupine Ergometer超声心动图1026评估冠状动脉疾病诊断的主要限制在主动脉上的动脉粥样硬化的特征纵向变化导管主动脉瓣植入使用经食道echocardiographyP1027Severe主动脉瓣狭窄：由两个和三个有效和解剖主动脉瓣区域之间的比较尺寸经食道ecocardiographyP1028Region生长方法提供了更好的左心室体积和cardaic输出measuringP10293维超声心动图评估二尖瓣患者的心室应变测量，并在患者就诊时肥厚cardiomyopathyP1031Left室劳损性心律失常的风险评估利率调整区域的中小学二尖瓣regurgitationP1030The影响阀几何预测长期结局ALCAPA patientsP1032Global心房心室株为新的索引高血压和糖尿病患者亚临床左心功能障碍</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-journal-lung-cancer_thesis/0201236695961.html">VEGF-D基因在肺腺癌、吉非替尼继发耐药肺腺癌及正常肺组织中的表达</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=王震&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . 王震</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=吴一龙&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,吴一龙</a> <a 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