Label-Free Quantification Mass Spectrometry Identifies Protein Markers of Chemotherapy Response in High-Grade Serous Ovarian Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37046833", "kind": "science-record", "revision": 2, "content_hash": "sha256:d8b142b23f7af13821098fc814142a4ce8cb06ca8006a677e8f5cf7173914bcb", "created_at": "2026-11-01T19:01:42Z", "updated_at": "2026-11-01T21:30:32Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Label-Free Quantification Mass Spectrometry Identifies Protein Markers of Chemotherapy Response in High-Grade Serous Ovarian Cancer.", "doi": "10.3390/cancers15072172", "pmid": "37046833", "authors": ["Georgia Arentz", "Parul Mittal", "Manuela Klingler-Hoffmann", "Mark R Condina", "Carmela Ricciardelli", "Noor A Lokman", "Gurjeet Kaur", "Martin K Oehler", "Peter Hoffmann"], "journal": "Cancers", "year": 2023, "abstract": "Eighty percent of ovarian cancer patients initially respond to chemotherapy, but the majority eventually experience a relapse and die from the disease with acquired chemoresistance. In addition, 20% of patients do not respond to treatment at all, as their disease is intrinsically chemotherapy resistant. Data-independent acquisition nano-flow liquid chromatography-mass spectrometry (DIA LC-MS) identified the three protein markers: gelsolin (GSN), calmodulin (CALM1), and thioredoxin (TXN), to be elevated in high-grade serous ovarian cancer (HGSOC) tissues from patients that responded to chemotherapy compared to those who did not; the differential expression of the three protein markers was confirmed by immunohistochemistry. Analysis of the online GENT2 database showed that mRNA levels of GSN, CALM1, and TXN were decreased in HGSOC compared to fallopian tube epithelium. Elevated levels of GSN and TXN mRNA expression correlated with increased overall and progression-free survival, respectively, in a Kaplan-Meier analysis of a large online repository of HGSOC patient data. Importantly, differential expression of the three protein markers was further confirmed when comparing parental OVCAR-5 cells to carboplatin-resistant OVCAR-5 cells using DIA LC-MS analysis. Our findings suggest that GSN, CALM1, and TXN may be useful biomarkers for predicting chemotherapy response and understanding the mechanisms of chemotherapy resistance. Proteomic data are available via ProteomeXchange with identifier PXD033785.", "claims": [{"id": "claim-method", "statement": "The quantification was performed using the summed area intensity of each peptide in each sample and the standard deviations and p values using un-paired t-tests were calculated using the GraphPad Prism 6 v008 (GraphPad Software, La Jolla, CA, USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37046833", "locator": "sections[9] \"2.7. Quantification of Protein(s) of Interest by DIA Nano-LC-ESI-MS\" paragraph 2", "quote": "The quantification was performed using the summed area intensity of each peptide in each sample and the standard deviations and p values using un-paired t-tests were calculated using the GraphPad Prism 6 v008 (GraphPad Software, La Jolla, CA, USA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [41] partner repository with the dataset identifier PXD033785 and 10.6019/PXD033785.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37046833", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [41] partner repository with the dataset identifier PXD033785 and 10.6019/PXD033785."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In DIA LC-MS analysis of patient tissues, GSN, CALM1, and TXN were significantly increased in chemotherapy-responsive HGSOC patients compared with non-responsive patients, with fold changes of 1.84, 2, and 2.47, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37046833", "locator": "sections[13] \"3.1. Identification of Protein Markers of Innate Chemoresistance by DIA LC-MS\" paragraph 3", "quote": "Following manual checking of the peptide matches in Skyline, GSN (fold change = 1.84, p value = 0.035), CALM1 (fold change = 2, p value = 0.029), and TXN (fold change = 2.47, p value = 0.0086) were found to be significantly increased in the cohort of patients who responded to chemotherapy compared to those who did not."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In DIA LC-MS analysis of patient tissues, GSN, CALM1, and TXN were significantly increased in chemotherapy-responsive HGSOC patients compared with non-responsive patients, with fold changes of 1.84, 2, and 2.47, respectively.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37046833"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD033785"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:PXD033785"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37046833", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/cancers15072172", "sha256": "sha256:cfdc4ee1405db23d591790f23d1d055d1fbbedb5a26dd59322d5aedf46e850ec", "bytes": 47369, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/cancers15072172", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10093294", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:PXD033785", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=PXD033785", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "PXD033785", "version": null, "note": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [41] partner repository with the dataset identifier PXD033785 and 10.6019/PXD033785.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [41] partner repository with the dataset identifier PXD033785 and 10.6019/PXD033785.", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": "Label Free Quantification Mass Spectrometry Identifies Protein Markers of Chemoresistance in Serous Ovarian Cancer", "resolution_checked_at": "2026-11-01T18:46:41Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:PXD033785 not downloaded", "asset:data:geo:PXD033785 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-2", "family": null, "specific": null, "label": "un-paired t-tests", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The quantification was performed using the summed area intensity of each peptide in each sample and the standard deviations and p values using un-paired t-tests were calculated using the GraphPad Prism 6 v008 (GraphPad Software, La Jolla, CA, USA)."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["survival_km"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: kaplan_meier."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["PXD033785", "PXD033785 and 10.6019/PXD033785"], "resolved_accessions": ["PXD033785"], "statements": ["The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE [41] partner repository with the dataset identifier PXD033785 and 10.6019/PXD033785."], "basis": "The paper names PXD033785 in ProteomeXchange Consortium and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["survival_km"], "assets": ["source:pmid:37046833", "data:geo:PXD033785"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:PXD033785"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:36:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 14488, "completion_tokens": 2449, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37046833", "type": "paper", "label": "pmid:37046833"}, {"id": "source:pmid:37046833", "type": "manuscript", "label": "PMID 37046833 full text"}, {"id": "data:geo:PXD033785", "type": "dataset", "label": "GEO PXD033785"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37046833", "type": "paper", "label": "pmid:37046833"}, {"id": "source:pmid:37046833", "type": "manuscript", "label": "PMID 37046833 full text"}, {"id": "data:geo:PXD033785", "type": "dataset", "label": "GEO PXD033785"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37046833", "type": "extraction", "used": ["source:pmid:37046833"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-PXD033785", "type": "accession_resolution", "used": ["data:geo:PXD033785"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:37046833", "parent_hash": "sha256:ad4cf2aa28f42c1bbb5040ef52578595a6021c7b9de7991f2160d0242548d8e1", "fork_of": null, "generation": 1}, "gaps": ["asset:data:geo:PXD033785 licence not read", "asset:data:geo:PXD033785 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Label-Free Quantification Mass Spectrometry Identifies Protein Markers of Chemotherapy R", "acquisition nano-flow liquid chromatography-mass spectrometry (DIA LC-MS) identified the three protein mar", "g the mechanisms of chemotherapy resistance. Proteomic data are available via ProteomeXchange with"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["f the three protein markers was confirmed by immunohistochemistry. Analysis of the online GENT2 database showe"], "order_basis": "paper_text_order:798", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["survival_km"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["Kaplan-Meier"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}