Background: Pancreatic ductal adenocarcinoma (PDAC) remains a formidable health challenge due to its detection at a late stage and a lack of reliable biomarkers for early detection. Although levels of carbohydrate antigen 19-9 are often used in conjunction with imaging-based tests to aid in the diagnosis of PDAC, there is still a need for more sensitive and specific biomarkers for early detection of PDAC.
Methods: We obtained serum samples from 88 subjects (patients with PDAC (n = 58) and controls (n = 30)). We carried out a multi-omics analysis to measure cytokines and related proteins using proximity extension technology and lipidomics and metabolomics using tandem mass spectrometry. Statistical analysis was carried out to find molecular alterations in patients with PDAC and a machine learning model was used to derive a molecular signature of PDAC.
Results: We quantified 1,462 circulatory proteins along with 873 lipids and 1,001 metabolites. A total of 505 proteins, 186 metabolites and 33 lipids including bone marrow stromal antigen 2 (BST2), keratin 18 (KRT18), and cholesteryl ester(20:5) were found to be significantly altered in patients. We identified different levels of sphingosine, sphinganine, urobilinogen and lactose indicating that glycosphingolipid and galactose metabolisms were significantly altered in patients compared to controls. In addition, elevated levels of diacylglycerols and decreased cholesteryl esters were observed in patients. Using a machine learning model, we identified a signature of 38 biomarkers for PDAC, composed of 21 proteins, 4 lipids, and 13 metabolites.
Conclusions: Overall, this study identified several proteins, metabolites and lipids involved in various pathways including cholesterol and lipid metabolism to be changing in patients. In addition, we discovered a multi-analyte signature that could be further tested for detection of PDAC.
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Cancer Gene Ther
December 2024
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.
Angiosarcomas are a group of vascular cancers that form malignant blood vessels. These malignancies are seemingly inflamed primarily due to their pathognomonic nature, which consists of irregular endothelium and tortuous blood channels. PIK3CA mutations are oncogenic and disrupt the PI3K pathway.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
December 2024
Universidade Federal do Rio Grande do Norte, IMD, Ppg-Bioinformatica, Natal, Brazil; University of Southern California, Keck School of Medicine, Department of Translational Genomics, 1450 Biggy St., Los Angeles, CA 90089, United States of America. Electronic address:
Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer representing approximately 25 % of all uterine malignancies. The molecular heterogeneity and pathogenesis of uLMS are not well understood, and translational studies aimed at discovering the vulnerabilities of this tumor type are of high priority. We conducted an innovative comprehensive multi-omics integration study from DNA to protein using freshly frozen tumors.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Research Institute of Pomology, Chinese Academy of Agricultural Sciences, Xingcheng, Liaoning Province 125100, China. Electronic address:
The UGT72 gene family encodes proteins that glycosylate phenylpropanoids, and thus contribute to the synthesis of various phenolic substances. However, their functional role and evolutionary history in Pyrus spp. remains poorly understood.
View Article and Find Full Text PDFSci Total Environ
December 2024
School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China. Electronic address:
Environmental heavy metal contamination, combined with inappropriate use of fungicides, has led to the co-existence of lead (Pb) and iprodione (IPR), presenting signification risks to ecosystems and human health. The toxic effects resulting from concurrent exposure to Pb and IPR, however, remain poorly understood. In the study, we conducted a comprehensive 60-day subchronic study to investigate the toxic effects on the liver and gut in parental male zebrafish through employing multi-omics analyses.
View Article and Find Full Text PDFBiol Direct
December 2024
Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3 Qingchun Road, Hangzhou, 310016, China.
Background: Precision oncology's implementation in clinical practice faces significant constraints due to the inadequacies in tools for detailed patient stratification and personalized treatment methodologies. Dysregulated tryptophan metabolism has emerged as a crucial factor in tumor progression, encompassing immune suppression, proliferation, metastasis, and metabolic reprogramming. However, its precise role in clear cell renal cell carcinoma (ccRCC) remains unclear, and predictive models or signatures based on tryptophan metabolism are conspicuously lacking.
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