5-Fluorouracil resistant CRC cells derived exosomes promote cancer-associated fibroblasts secreting more CXCL12.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38817851", "kind": "science-record", "revision": 3, "content_hash": "sha256:ee6665861ef69b5faf5225b1e4f992bd97dc828b11d008ab4a435f02c5e5fb7f", "created_at": "2026-11-01T19:20:46Z", "updated_at": "2026-11-01T22:11:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "5-Fluorouracil resistant CRC cells derived exosomes promote cancer-associated fibroblasts secreting more CXCL12.", "doi": "10.7150/jca.95248", "pmid": "38817851", "authors": ["Tongxin Zhang", "Zilong He", "Xiaowei Qi", "Yu Zhang", "Yankui Liu", "Linfang Jin", "Teng Wang"], "journal": "Journal of Cancer", "year": 2024, "abstract": "Background: Chemoresistance is a key reason for treatment failure in colorectal cancer (CRC) patients. The tumor microenvironment of chemoresistant CRC is distinctly immunosuppressive, although the underlying mechanisms are unclear. Methods: The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method. The in-situ expression of transient receptor potential channel 5 (TRPC5) and fibroblast activation protein (FAP) in the CRC tissues was examined by immunohistochemistry. TRPC5 expression levels in the HCT8 and HCT116 cell lines and the corresponding 5-fluorouracil (5-FU)-resistant cell lines (HCT8R and HCT116R) were analyzed by western blotting and RT-PCR. Exosomes were isolated from the HCT8R and HCT116R cells and incubated with colorectal normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs)markers were detected. NFs were also incubated with exosomes isolated from TRPC5-knockdown HCT8R cells, and the changes in intracellular Ca2+ levels and C-X-C motif chemokine ligand 12 (CXCL12) secretion were analyzed. Results: TRPC5 and FAP expression showed positive correlation in the datasets. Immunostaining of CRC tissue specimens further revealed that high TRPC5 and FAP expressions were significantly associated with worse tumor regression. Furthermore, chemoresistant CRC cells expressed higher levels of TRPC5 compared to the chemosensitive cells, and knocking down TRPC5 reversed chemoresistance. Exosomes derived from CRC cells induced the transformation of NFs to CAFs. However, TRPC5-exosomes derived from chemoresistant CRC cells can promote CAFs to secrete more CXCL12. Conclusion: Chemoresistant CRC cells can induce CAFs activation and promote CXCL12 secretion through exosomal TRPC5.", "claims": [{"id": "claim-method", "statement": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38817851", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38817851", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method."}], "state": "complete"}, {"id": "claim-target-result", "statement": "TRPC5 and FAP expression showed positive correlation in the datasets.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38817851", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "TRPC5 and FAP expression showed positive correlation in the datasets."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "TRPC5 and FAP expression showed positive correlation in the datasets.", "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:38817851"], "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:GSE62080"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:student_t", "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:GSE62080"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:student_t"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38817851", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7150/jca.95248", "sha256": "sha256:6ffefeab20306a4095f5e675436e503a91e7514393c5573a2ec8ec86adff933d", "bytes": 39755, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7150/jca.95248", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11134431", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE62080", "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=GSE62080", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62080", "version": null, "note": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1519418", "GSM1519419", "GSM1519420", "GSM1519421", "GSM1519422", "GSM1519423", "GSM1519424", "GSM1519425", "GSM1519426", "GSM1519427", "GSM1519428", "GSM1519429", "GSM1519430", "GSM1519431", "GSM1519432", "GSM1519433", "GSM1519434", "GSM1519435", "GSM1519436", "GSM1519437", "GSM1519438"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE69657", "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=GSE69657", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE69657", "version": null, "note": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1705389", "GSM1705390", "GSM1705391", "GSM1705392", "GSM1705393", "GSM1705394", "GSM1705395", "GSM1705396", "GSM1705397", "GSM1705398", "GSM1705399", "GSM1705400", "GSM1705401", "GSM1705402", "GSM1705403", "GSM1705404", "GSM1705405", "GSM1705406", "GSM1705407", "GSM1705408", "GSM1705409", "GSM1705410", "GSM1705411", "GSM1705412", "GSM1705413", "GSM1705414", "GSM1705415", "GSM1705416", "GSM1705417", "GSM1705418"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Identification of HOXB8 and K LK11 expression levels as potential biomarkers to predict the effects of FOLFOX4 chemotherapy", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE62080 not downloaded", "asset:data:geo:GSE62080 licence not read", "asset:data:geo:GSE69657 not downloaded", "asset:data:geo:GSE69657 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "student_t_test", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["student_t"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Student's t-test"}}, {"id": "method-2", "family": null, "specific": null, "label": "Pearson method", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.student_t"]}, "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": false, "required_operations": [], "missing_operations": ["student_t"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: student_t_test."}, "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": ["GSE69657", "GSE62080"], "resolved_accessions": ["GSE69657", "GSE62080"], "statements": ["The CRC data sets GSE69657 and GSE62080 were downloaded from the GEO database, and the correlation between TRPC5 and FAP expression was analyzed by Pearson method."], "basis": "The paper names GSE69657, GSE62080 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:38817851", "data:geo:GSE62080"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "student_t", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE62080"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:20:09Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 12272, "completion_tokens": 867, "cached_tokens": 128}}, "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:38817851", "type": "paper", "label": "pmid:38817851"}, {"id": "source:pmid:38817851", "type": "manuscript", "label": "PMID 38817851 full text"}, {"id": "data:geo:GSE62080", "type": "dataset", "label": "GEO GSE62080"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38817851", "type": "paper", "label": "pmid:38817851"}, {"id": "source:pmid:38817851", "type": "manuscript", "label": "PMID 38817851 full text"}, {"id": "data:geo:GSE62080", "type": "dataset", "label": "GEO GSE62080"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38817851", "type": "extraction", "used": ["source:pmid:38817851"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE62080", "type": "accession_resolution", "used": ["data:geo:GSE62080"], "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:38817851", "parent_hash": "sha256:9a0a309fd0bd61269ab7c598b4ef98714d7e1f308eab87e70bfc8d35c772378e", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE62080 licence not read", "asset:data:geo:GSE62080 not downloaded", "asset:data:geo:GSE69657 licence not read", "asset:data:geo:GSE69657 not downloaded", "execution.not_run", "method.reader_named_unmapped", "method.student_t", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:run_analysis blocked on method:student_t"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ein (FAP) in the CRC tissues was examined by immunohistochemistry. TRPC5 expression levels in the HCT8 and HCT", "showed positive correlation in the datasets. Immunostaining of CRC tissue specimens further revealed tha", "imens and postoperative tissue specimens for immunostaining. The AJCC tumor regression grading (TRG) sys"], "order_basis": "paper_text_order:622", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["l lines (HCT8R and HCT116R) were analyzed by western blotting and RT-PCR. Exosomes were isolated from the"], "order_basis": "paper_text_order:804", "id": "assay:2"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["incubated with exosomes isolated from TRPC5-knockdown HCT8R cells, and the changes in intracellula"], "order_basis": "paper_text_order:1067", "id": "assay:3"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["(Zhejiang, China). HCT8 and HCT8R cells were cultured in RPMI-1640 medium (CTCC-002-123, MeisenCTCC),", "02-123, MeisenCTCC), and CCD-Co18 cells were cultured in DMEM (CTCC-002-084, MeisenCTCC). In addition", "n addition, the HCT8R and HCT116R cells were cultured in DMEM supplemented with 0.5µg/ml and 0.8µg/ml"], "order_basis": "paper_text_order:2228", "id": "assay:4"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Student's t-test"], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}