TGM2, HMGA2, FXYD3, and LGALS4 genes as biomarkers in acquired oxaliplatin resistance of human colorectal cancer: A systems biology approach.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37535601", "kind": "science-record", "revision": 5, "content_hash": "sha256:6f40903387fbbdafc140b7b00e06f390970f8ddebdbc54d3e86d44356d9d8302", "created_at": "2026-11-01T19:02:18Z", "updated_at": "2026-11-01T22:52:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "TGM2, HMGA2, FXYD3, and LGALS4 genes as biomarkers in acquired oxaliplatin resistance of human colorectal cancer: A systems biology approach.", "doi": "10.1371/journal.pone.0289535", "pmid": "37535601", "authors": ["Tayebeh Cheraghi-Shavi", "Razieh Jalal", "Zarrin Minuchehr"], "journal": "PloS one", "year": 2023, "abstract": "Acquired resistance to oxaliplatin is considered as the primary reason for failure in colorectal cancer (CRC) therapy. Identifying the underlying resistance mechanisms may improve CRC treatment. The present study aims to identify the key genes involved in acquired oxaliplatin-resistant in CRC by confirming the oxaliplatin resistance index (OX-RI). To this aim, two public microarray datasets regarding oxaliplatin-resistant CRC cells with different OX-RI, GSE42387, and GSE76092 were downloaded from GEO database to identify differentially expressed genes (DEGs). The results indicated that the OX-RI affects the gene expression pattern significantly. Then, 54 common DEGs in both datasets including 18 up- and 36 down-regulated genes were identified. Protein-protein interaction (PPI) analysis revealed 13 up- (MAGEA6, TGM2, MAGEA4, SCHIP1, ECI2, CD33, AKAP12, MAGEA12, CALD1, WFDC2, VSNL1, HMGA2, and MAGEA2B) and 12 down-regulated (PDZK1IP1, FXYD3, ALDH2, CEACAM6, QPRT, GRB10, TM4SF4, LGALS4, ALDH3A1, USH1C, KCNE3, and CA12) hub genes. In the next step, two novel up-regulated hub genes including ECI2 and SCHIP1 were identified to be related to oxaliplatin resistance. Functional enrichment and pathway analysis indicated that metabolic pathways, proliferation, and epithelial-mesenchymal transition may play dominant roles in CRC progression and oxaliplatin resistance. In the next procedure, two in vitro oxaliplatin-resistant sub-lines including HCT116/OX-R4.3 and HCT116/OX-R10 cells with OX-IR 3.93 and 10.06 were established, respectively. The results indicated the up-regulation of TGM2 and HMGA2 in HCT116/OX-R10 cells with high OX-RI and down-regulation of FXYD3, LGALS4, and ECI2 in both cell types. Based on the results, TGM2, HMGA2, FXYD3, and LGALS4 genes are related to oxaliplatin-resistant CRC and may serve as novel therapeutic targets.", "claims": [{"id": "claim-method", "statement": "All of the data were expressed as the mean ± standard deviation (SD). The statistical comparisons were performed utilizing Student’s t-test and one-way ANOVA were applied for comparing two and three or more groups using GraphPad Prism 9.5.0 1 (GraphPad Software, LLC).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37535601", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "All of the data were expressed as the mean ± standard deviation (SD). The statistical comparisons were performed utilizing Student’s t-test and one-way ANOVA were applied for comparing two and three or more groups using GraphPad Prism 9.5.0 1 (GraphPad Software, LLC)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The microarray data of GSE42387 are based on GPL16297 platform (Agilent-014850 Whole Human Genome Microarray 4x44K G4112F), and the OX-RI value equals 107 [43]. The array data for GSE76092 are based on GPL2125 platform (HumanV2GE 8x60k Microarrays, Agilent design ID: 039494 (original reference: GPL19775 and GPL19773)), and the OX-RI value equals 4.61 [44]. Totally, six samples were obtained for the following analysis, which contained three acquired oxaliplatin-resistant HT-29 cells and three oxaliplatin-sensitive HT-29 samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37535601", "locator": "sections[15] \"Selecting datasets and identifying DEGs\" paragraph 4", "quote": "The microarray data of GSE42387 are based on GPL16297 platform (Agilent-014850 Whole Human Genome Microarray 4x44K G4112F), and the OX-RI value equals 107 [43]. The array data for GSE76092 are based on GPL2125 platform (HumanV2GE 8x60k Microarrays, Agilent design ID: 039494 (original reference: GPL19775 and GPL19773)), and the OX-RI value equals 4.61 [44]. Totally, six samples were obtained for the following analysis, which contained three acquired oxaliplatin-resistant HT-29 cells and three oxaliplatin-sensitive HT-29 samples."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Then, 54 common DEGs in both datasets including 18 up- and 36 down-regulated genes were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37535601", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Then, 54 common DEGs in both datasets including 18 up- and 36 down-regulated genes were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Then, 54 common DEGs in both datasets including 18 up- and 36 down-regulated genes were identified.", "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:37535601"], "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:GSE42387"], "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:GSE42387"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37535601", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0289535", "sha256": "sha256:d373d9da4157786a2c6d67738d8ec33baf92f3dff2f5dac9a4e7e5e7245fb13c", "bytes": 50907, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0289535", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10399784", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE42387", "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=GSE42387", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE42387", "version": null, "note": "The microarray data of GSE42387 are based on GPL16297 platform (Agilent-014850 Whole Human Genome Microarray 4x44K G4112F), and the OX-RI value equals 107 [43]. 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