Nanomaterials augmented LDI-TOF-MS for pancreatic ductal adenocarcinoma diagnosis and classification.

医学 胰腺癌 癌症 胰腺导管腺癌 假阳性悖论 腺癌 病理 内科学 人工智能 计算机科学
作者
Yaolin Xu,Dansong Wang,Tiantao Kuang,Wenchuan Wu,Xuefeng Xu,Dayong Jin,Hua Zhang,Sheng Zhong,Yunbing Wang,Wenhui Lou
出处
期刊:Journal of Clinical Oncology [American Society of Clinical Oncology]
卷期号:38 (15_suppl): e16761-e16761
标识
DOI:10.1200/jco.2020.38.15_suppl.e16761
摘要

e16761 Background: Pancreatic ductal adenocarcinoma (PAAD) is one type of cancer with poor prognosis. Although CA 19-9 was the most common serological marker for cancer screening and surveillance after treatment, there are still unignorable limitations, including low sensitivity, possible false-negatives/positives owing to confounding conditions. Reliable non-invasive diagnostics is in urgent need. As PAAD is increasingly considered as a metabolic disorder, serum metabolite profiling is becoming critical to reveal important cancer-related bioinformation. This work proposes a novel LDI-TOF-MS technique for PAAD screening and diagnosis. Methods: An LDI-TOF-MS platform was established for cancer screening. All mass spectrum was collected within a mass range of 100 to 1,100 Da, while the spectra were manually examined using the FlexAnalysis 3.4 software (Bruker Daltonics, Bremen, Germany). In a typical process, 0.5 uL of serum samples were spotted on a polished steel target plate MTP 384 and air-dried followed by another 1 uL of GNS or SiNW nanomaterials. The spectra were then acquired in the reflection positive mode with smartbeam-II laser at 355 nm with laser frequency of 1,000 Hz. A random walk of 25 shots at raster spot and 20 different spots were measured for each individual sample, therefore, 500 satisfactory shots were obtained. Results: By taking advantage of 3D nanostructures and machine learning, we applied proposed approach to 94 patients with PAAD, as well as 203 healthy controls (Table). The results demonstrated an average sensitivity of 99% and a specificity over 98% in detecting cancers. 11 of 94 PAAD patients (11.70%) were CA 19-9 negative (CA19-9 < 37U/ml, stage I n = 2, stage II n = 7, stage III n = 1 and stage IV n = 1). LDI-TOF-MS recognized almost all CA 19-9-negative PAAD. The sensitivity and specificity were obviously superior to CA 19-9 in PAAD: only 1 of 94 PAAD (1.06%) were misclassified as healthy controls. In contrast, CA19-9 positive and CA 19-9 negative PAADs were not readily distinguished by this method. Therefore, this method was independent of tumor markers. Conclusions: Result suggested strong potential of proposed technique as a low-cost, superior precision, and high-throughput procedure for PAAD diagnosis and beyond. [Table: see text]

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