Identification of diagnostic markers and lipid dysregulation in oesophageal squamous cell carcinoma through lipidomic analysis and machine learning

Yuan, Yuyao; Zhao, Zitong; Xue, Liyan; Wang, Guangxi; Song, Huajie; Pang, Ruifang; Zhou, Juntuo; Luo, Jianyuan; Song, Yongmei; Yin, Yuxin

doi:10.1038/s41416-021-01395-w

Cited by 14 publications

(11 citation statements)

References 35 publications

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“…In recent years, as development in algorithms, machine learning is becoming more and more widely employed in data mining procedures of metabolomics to retrieve biomarker panels for better performance ( Reel et al, 2021 ; Li et al, 2022 ). For example, researchers have used support vector machine (SVM)-based machine learning models to illustrate diagnostic biomarkers in blood for oesophageal cancer ( Yuan et al, 2021 ), pancreatic cancer ( Wang et al, 2021 ), lung cancer ( Wang et al, 2022 ) and brain glioma ( Zhou et al, 2022 ). The SVM-based algorithm can rank all potential biomarkers according to their weight in the model, making it practical to optimize the candidates for a biomarker panel.…”

Section: Discussionmentioning

confidence: 99%

“…Metabolomic studies have made great progresses recently in tumor diagnosis. Yuan et al (2021) combined serum lipidomics to reveal lipid biomarkers for detection of oesophageal squamous cell carcinoma, and a panel of 12 lipids were finally found for diagnostic purpose. Wang et al (2021) employed metabolomics in search for blood diagnostic biomarkers of pancreatic ductal adenocarcinoma and early-stage lung adenocarcinoma ( Wang et al, 2022 ), revealing 17 and 9 potential lipid markers in blood separately.…”

Section: Introductionmentioning

confidence: 99%

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Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine

Zhou¹,

Zhong

2022

Front. Mol. Biosci.

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Metabolomics is a fast-developing technique used in biomedical researches focusing on pathological mechanism illustration or novel biomarker development for diseases. The ability of simultaneously quantifying thousands of metabolites in samples makes metabolomics a promising technique in predictive or personalized medicine-oriented researches and applications. Liquid chromatography-mass spectrometry is the most widely employed analytical strategy for metabolomics. In this current mini-review, we provide a brief update on the recent developments and novel applications of LC-MS based metabolomics in the predictive and personalized medicine sector, such as early diagnosis, molecular phenotyping or prognostic evaluation. COVID-19 related metabolomic studies are also summarized. We also discuss the prospects of metabolomics in precision medicine-oriented researches, as well as critical issues that need to be addressed when employing metabolomic strategy in clinical applications.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine

Zhou¹,

Zhong

2022

Front. Mol. Biosci.

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“…We were able to identify correlations between pathological conditions, expression of DPPC, and expression of ANXA2 in a variety of reports (Table 1). Both increased DPPC and decreased ANXA2 have been associated with esophageal cancer, 84,85 osteosarcoma, 86,87 and non‐malignance of salivary tumors 88,89 . Also interesting is a possible association of DPPC and ANXA2 in both lupus and preeclampsia, where increased DPPC can accumulate to form “active hydrophobic spots,” possibly in conjunction with antiphospholipid syndrome and development of autoantibodies against ANXA2 90–94 .…”

Section: Discussionmentioning

confidence: 99%

Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation

et al. 2022

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The intersection of protein and lipid biology is of growing importance for understanding how cells address structural challenges during adhesion and migration. While protein complexes engaged with the cytoskeleton play a vital role, support from the phospholipid membrane is crucial for directing localization and assembly of key protein complexes. During angiogenesis, dramatic cellular remodeling is necessary for endothelial cells to shift from a stable monolayer to invasive structures. However, the molecular dynamics between lipids and proteins during endothelial invasion are not defined. Here, we utilized cell culture, immunofluorescence, and lipidomic analyses to identify a novel role for the membrane binding protein Annexin A2 (ANXA2) in modulating the composition of specific membrane lipids necessary for cortical F‐actin organization and adherens junction stabilization. In the absence of ANXA2, there is disorganized cortical F‐actin, reduced junctional Arp2, excess sprout initiation, and ultimately failed sprout maturation. Furthermore, we observed reduced filipin III labeling of membrane cholesterol in cells with reduced ANXA2, suggesting there is an alteration in phospholipid membrane dynamics. Lipidomic analyses revealed that 42 lipid species were altered with loss of ANXA2, including an accumulation of phosphatidylcholine (16:0_16:0). We found that supplementation of phosphatidylcholine (16:0_16:0) in wild‐type endothelial cells mimicked the ANXA2 knock‐down phenotype, indicating that ANXA2 regulated the phospholipid membrane upstream of Arp2 recruitment and organization of cortical F‐actin. Altogether, these data indicate a novel role for ANXA2 in coordinating events at endothelial junctions needed to initiate sprouting and show that proper lipid modulation is a critical component of these events.

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“…Interestingly, we were able to identify correlations between pathological conditions, expression of DPPC, and expression of ANXA2 in a variety of reports (Table 2). Both increased DPPC and decreased ANXA2 have been associated with esophageal cancer, 75, 76 osteosarcoma, 77, 78 and non-malignance of salivary tumors. 79, 80 Also interesting is a possible association of DPPC and ANXA2 in both lupus and preeclampsia, where increased DPPC can accumulate to form “active hydrophobic spots,” possibly in conjunction with antiphospholipid syndrome and development of autoantibodies against ANXA2.…”

Section: Discussionmentioning

confidence: 99%

Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation

Sveeggen

Abbey

Smith

et al. 2022

Preprint

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The intersection of protein and lipid biology is of growing importance for understanding how cells address structural challenges during adhesion and migration. While protein complexes engaged with the cytoskeleton play a vital role, support from the phospholipid membrane is crucial for directing localization and assembly of key protein complexes. During angiogenesis, it is well observed that dramatic cellular remodeling is necessary for endothelial cells to shift from a stable monolayer to invasive structures. However, the molecular dynamics between lipids and proteins during endothelial invasion are not defined. Here, we utilized cell culture, immunofluorescence, and lipidomic analyses to identify a novel role for the membrane binding protein Annexin A2 (ANXA2) in modulating the composition of specific membrane lipids necessary for cortical F-actin organization and adherens junction stabilization. In the absence of ANXA2, there is disorganized cortical F-actin, reduced junctional Arp2, excess sprout initiation, and ultimately failed sprout maturation. Further, we observed reduced filipin III labeling of membrane cholesterol in cells with reduced ANXA2, suggesting there is an alteration in phospholipid membrane dynamics. Lipidomic analyses reveal that 42 lipid species are altered with loss of ANXA2, including an accumulation of phosphatidylcholine (16:0_16:0). We find that supplementation of phosphatidylcholine (16:0_16:0) in wild-type endothelial cells mimics the ANXA2 knock-down phenotype, indicating that ANXA2 regulates the phospholipid membrane upstream of Arp2 recruitment and organization of cortical F-actin. Altogether these data indicate a novel role for ANXA2, and show that proper lipid modulation is a critical component of endothelial sprouting.

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Identification of diagnostic markers and lipid dysregulation in oesophageal squamous cell carcinoma through lipidomic analysis and machine learning

Cited by 14 publications

References 35 publications

Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine

Applications of liquid chromatography-mass spectrometry based metabolomics in predictive and personalized medicine

Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation

Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation

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