Dataset Information

DNA-Protein Crosslinking Problem in Saccharomyces cerevisiae for methanol utilization

ABSTRACT: Formaldehyde-induced DNA-protein crosslinkings (DPCs) and large repeated DNA fragments suggest strategies for methanol detoxification and phenotype enhancement

INSTRUMENT(S):

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Wei Zhong

LAB HEAD: Yajie Wang

PROVIDER: PXD064984 | Pride | 2026-01-07

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	HT_MSP2500025_25_10_methanol0.66_Slot1-37_1_4112.d.zip	Other
	HT_MSP2500025_25_10_methanol0.66_Slot1-37_1_4112.mzBIN	Other
	HT_MSP2500025_25_10_methanol0.66_Slot1-37_1_4112_calibrated.mzML	Mzml
	HT_MSP2500025_25_10_methanol0.66_Slot1-37_1_4112_uncalibrated.mzML	Mzml
	HT_MSP2500025_25_20_glc3.68_Slot1-35_1_4108.d.zip	Other

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Project description:Background & Aims: Cholangiocarcinomas (CCAs), heterogeneous biliary tumors with dismal prognosis, lack accurate early-diagnostic methods, especially important for individuals at high-risk (i.e., primary sclerosing cholangitis (PSC)). Here, we searched for protein biomarkers in serum extracellular vesicles (EVs). Methods: EVs from patients with isolated PSC (n=45), concomitant PSC-CCA (n=42), PSC who developed CCA during follow-up (PSC to CCA; n=25), CCAs from non-PSC etiology (n=56), hepatocellular carcinoma (n=34) and healthy individuals (n=55) were characterized by mass-spectrometry. Diagnostic biomarkers of PSC-CCA, non-PSC CCA or CCAs regardless etiology (pan-CCAs) were defined, and their expression was evaluated in human organs/tissues and within CCA tumors at single-cell level. Prognostic EV-biomarkers for CCA were investigated. Results: High-throughput proteomics identified candidate diagnostic biomarkers for PSC-CCA, non-PSC CCA or pan-CCA, as well as and for differential diagnosis of intrahepatic CCA and HCC, that were cross-validated by ELISA using total serum. Machine learning logit modelling disclosed CRP/FRIL/Fibrinogen algorithm with diagnostic value for early-stage PSC-CCA vs isolated PSC (AUC=0.944; OR=82.0), overpowering CA19-9 (AUC=0.735; OR=9.3). An algorithm combining CRP/VWF/PIGR/ /Fibrinogen allowed the diagnosis of early-stage non-PSC CCAs compared to healthy individuals (AUC=0.999; OR=1115). Noteworthy, levels of Fibrinogen/CRP/PIGR/FRIL showed predictive capacity for CCA development in patients with PSC before clinical evidences of malignancy. Multi-organ transcriptomic analysis revealed that serum EV-biomarkers were mostly expressed in hepatobiliary tissues, and scRNA-seq and immunofluorescence analysis of CCA tumors showed their presence mainly in malignant cholangiocytes. Multivariable analysis unveiled EVprognostic biomarkers independent to clinical features, with COMP/GNAI2/CFAI and ACTN1/MYCT1/PF4V associated negatively or positively to patients’ survival, respectively. Conclusions: Serum EVs contain protein biomarkers for the prediction, early diagnosis and prognosis estimation of CCA, representing a novel tumor cell-derived liquid biopsy for personalized medicine.

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DNA-Protein Crosslinking Problem in Saccharomyces cerevisiae for methanol utilization

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