High-performance Collective Biomarker from Liquid Biopsy for Diagnosis of Pancreatic Cancer Based on Mass Spectrometry and Machine Learning

Abstract

Background: Most pancreatic cancers are found at progressive stages when they cannot be surgically removed. Therefore, a highly accurate early detection method is urgently needed. Methods: This study analyzed serum from Japanese patients who suffered from pancreatic ductal adenocarcinoma (PDAC) and aimed to establish a PDAC-diagnostic system with metabolites in serum. Two groups of metabolites, primary metabolites (PM) and phospholipids (PL), were analyzed using liquid chromatography/electrospray ionization mass spectrometry. A support vector machine was employed to establish a machine learning-based diagnostic algorithm. Results: Integrating PM and PL databases improved cancer diagnostic accuracy and the area under the receiver operating characteristic curve. It was more effective than the algorithm based on either PM or PL database, or single metabolites as a biomarker. Subsequently, 36 statistically significant metabolites were fed into the algorithm as a collective biomarker, which improved results by accomplishing 97.4% and was further validated by additional serum. Interestingly, specific clusters of metabolites from patients with preoperative neoadjuvant chemotherapy (NAC) showed different patterns from those without NAC and were somewhat comparable to those of the control. Conclusion: We propose an efficient screening system for PDAC with high accuracy by liquid biopsy and potential biomarkers useful for assessing NAC performance.

Meta-Analysis Reveals Both the Promises and the Challenges of Clinical Metabolomics

“…A total of 24 metabolomics studies focused on identifying disease biomarkers from PDAC patients were compiled [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. The techniques used in each study, source of sample, and number of significantly identified metabolites are detailed in Table 1 .…”

“…Further, the lack of a comprehensive evaluation of these clinical studies hinders the identification of study design parameters that may negatively impact the reproducibility of the outcomes. To address these issues, we present a detailed analysis of 24 clinical pancreatic ductal adenocarcinoma (PDAC) metabolomics studies [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Our meta-analysis revealed an extensive variation in these studies and highlighted a substantial inconsistency in outcomes, but also identified a subset of metabolites that were identified across multiple datasets.…”

“…There is an urgent need to identify molecular biomarkers to assist in the diagnosis and prognosis of PDAC and to aid in monitoring a patient’s response to treatment. To date, there have been 24 PDAC metabolomics studies conducted to identify potential metabolite biomarkers [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ].…”

Pancreatic cancer, pancreatogenic diabetes, type 2 diabetes mellitus

“…и фосфолипиды, были проанализированы в работе Iwano T. (2021). В итоге в скрининговый алгоритм были включены 36 статистически значимых метаболитов (15 первичных метаболитов, включая орнитин, уридин, аспарагиновую кислоту, глутаминовую кислоту, ксантин, гипоксантин и др., и 28 фосфолипидов) в качестве коллективного биомаркера, что улучшило результаты на 97,4% [67].…”

Chemical Biopsy for GNMT as Noninvasive and Tumorigenesis-Relevant Diagnosis of Liver Cancer

“…Recent years have witnessed increased interest in liquid biopsy for cancer diagnosis due to its noninvasive nature. − Metabolomic analysis of bodily fluids, i.e., serum or urine, has been a popular approach and has prompted more than 1000 studies on cancer-diagnostic biomarkers. A related concept is “chemical biopsy,” which appeared in the literature more than five decades ago .…”