Dataset Information

Activity-based SWATH/DIA proteomic screen enables sensitive differential detection of serine hydrolases from surgically resected OCT-embedded primary lung adenocarcinoma

ABSTRACT: Lung malignancies are among the leading causes of cancer-related death in the modern world. While the disease is relatively manageable if caught at an early stage, the genomic variability and high level of mutations represent a daunting challenge for diagnosis, staging and prognostic classification. One of the hallmarks of lung cancer is dysregulated activity of serine hydrolases, nevertheless, detection of their activity is challenging because bio specimens are available mostly as OCT-embedded tissues and current limitations of analytical workflows. To address the need for a robust and sensitive activity-based proteomic workflow, we established an ABPP-SWATH/DIA-MS platform and applied it for depletion-dependent differential activity profiling of serine hydrolases on a cohort of lung cancer patient samples. We demonstrated it is compatible with sensitive activity-based studies from OCT-embedded tissues by monitoring over 170 hydrolases across the patient sample cohort identifying over 20 dysregulated hydrolases like PREP, DPPIV and ELANE that have elevated activity in tumours. We confirmed our findings with a fluorescent activity-based probe and activity assays to show that our platform can guide the selection of hydrolases for validation in biochemical assays. Importantly, the method could be applied to reinvestigate the existing collections of lung cancer samples for dysregulated hydrolases and thus improve understanding of molecular biology of cancer and select biomarkers for better disease diagnosis and staging

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

DISEASE(S): Lung Adenocarcinoma

SUBMITTER: Tatjana Sajic

LAB HEAD: Prof. Dr. Rudolf Aebersold

PROVIDER: PXD019357 | Pride | 2025-06-02

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	ConvertTSVToTraML__1_.TraML	Other
	E1907041634_feature_alignment_IntraTissue.tsv	Tabular
	E1907312103_feature_alignment_24_biopsies_SHlib.tsv	Tabular
	File_annotation.txt	Txt
	SAJICT_SH_ACTIVITY_E1906021247.prot__1_.xml	Xml

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Publications

Depletion-dependent activity-based protein profiling using SWATH/DIA-MS detects serine hydrolase lipid remodeling in lung adenocarcinoma progression.

Sajic Tatjana T Vizovišek Matej M Arni Stephan S Ciuffa Rodolfo R Mehnert Martin M Lenglet Sébastien S Weder Walter W Gallart-Ayala Hector H Ivanisevic Julijana J Buljan Marija M Thomas Aurelien A Hillinger Sven S Aebersold Ruedi R

Nature communications 20250527 1

Systematic inference of enzyme activity in human tumors is key to understanding cancer progression and resistance to therapy. However, standard protein or transcript abundances are blind to the activity status of the measured enzymes, regulated, for example, by active-site amino acid mutations or post-translational protein modifications. Current methods for activity-based proteome profiling (ABPP), which combine mass spectrometry (MS) with chemical probes, quantify the fraction of enzymes that a ...[more]

PMID: 40425563

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