A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife.
A novel methodology for in vivo endoscopic phenotyping of colorectal cancer based on real-time analysis of the mucosal lipidome: a prospective observational study of the iKnife.
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DOI：
10.1007/s00464-016-5121-5
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发表时间：
2017-03
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影响因子：
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通讯作者：
Takats Z
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作者：
Alexander J;Gildea L;Balog J;Speller A;McKenzie J;Muirhead L;Scott A;Kontovounisios C;Rasheed S;Teare J;Hoare J;Veselkov K;Goldin R;Tekkis P;Darzi A;Nicholson J;Kinross J;Takats Z
本初步研究评估了快速蒸发电离质谱（REIMS）在结直肠癌（CRC）和结肠腺瘤中的诊断准确性。在伦敦玛丽医院和英国皇家马斯登医院招募了接受择期手术切除CRC的患者。使用标准电外科手持件进行离体分析，其中将电外科气溶胶抽吸到Xevo G2-S iKnife QTof质谱仪（沃茨Corporation）。出于验证目的，进行了组织学检查。在Matlab 2015 a（Mathworks，Natick，MA）中使用主成分分析和线性判别分析进行多变量分析。开发了改良的REIMS内镜圈套器（Medwork），并在5例患者中前瞻性使用，以评估其在热圈套器息肉切除术中的可行性。招募了28名患者（12名男性，中位年龄71岁，范围35-89岁）。REIMS能够可靠地区分癌症和正常邻近粘膜（NAM）（AUC 0.96）以及NAM和腺瘤（AUC 0.99）。它检测癌症与腺瘤的总体准确性为94.4%，检测腺瘤的灵敏度为78.6%，特异性为97.3%（AUC 0.99）。长链磷脂酰丝氨酸（例如，PS 22：0）和细菌磷脂酰甘油在癌症样品上过表达，而NAM通过升高的缩醛磷脂和三酰甘油表达来定义，并且腺瘤表现出神经酰胺的过表达。REIMS能够根据肿瘤分化、肿瘤出芽、淋巴血管浸润、壁外血管浸润和淋巴结微转移对样品进行分类（AUC分别为0.88、0.87、0.83、0.81和0.81）。在内镜展开期间，结肠镜REIMS能够在热圈套息肉切除术期间检测靶脂质物质，例如神经酰胺。基于对粘膜脂质组的多变量分析，REIMS对肿瘤类型和CRC预后不良的既定组织学特征表现出较高的诊断准确性。REIMS可以增强内窥镜和成像技术，用于结直肠癌的精确表型。本文的在线版本（doi：10.1007/s 00464 -016-5121-5）包含补充材料，可供授权用户使用。
This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas. Patients undergoing elective surgical resection for CRC were recruited at St. Mary’s Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy. Twenty-eight patients were recruited (12 males, median age 71, range 35–89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC’s 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy. REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer. The online version of this article (doi:10.1007/s00464-016-5121-5) contains supplementary material, which is available to authorized users.