Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38439884", "kind": "science-record", "revision": 5, "content_hash": "sha256:452d216a9d9644dc995e07e4c2c07dd2306ca7114c7db020af5634216e1f8419", "created_at": "2026-11-01T19:20:23Z", "updated_at": "2026-11-01T22:53:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation.", "doi": "10.1016/j.heliyon.2024.e26604", "pmid": "38439884", "authors": ["Renwen Wan", "Yisheng Chen", "Xinting Feng", "Zhiwen Luo", "Zhen Peng", "Beijie Qi", "Haocheng Qin", "Jinrong Lin", "Shiyi Chen", "Liangfeng Xu", "Jiayin Tang", "Ting Zhang"], "journal": "Heliyon", "year": 2024, "abstract": "Background: Colorectal cancer (CRC) is the third most prevalent tumor globally. The liver is the most common site for CRC metastasis, and the involvement of the liver is a common cause of death in patients with late-stage CRC. Consequently, mitigating CRC liver metastasis (CRLM) is key to improving CRC prognosis and increasing survival. Exercise has been shown to be an effective method of improving the prognosis of many tumor types. However, the ability of exercise to inhibit CRLM is yet to be thoroughly investigated.\nMethods: The GSE157600 and GSE97084 datasets were used for analysis. A pan-cancer dataset which was uniformly normalized was downloaded and analyzed from the UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G = 60,499). Several advanced bioinformatics analyses were conducted, including single-cell sequencing analysis, correlation algorithm, and prognostic screen. CRC tumor microarray (TMA) as well as cell/animal experiments are used to further validate the results of the analysis.\nResults: The greatest variability was found in epithelial cells from the tumor group. RPS4X was generally upregulated in all types of CRC, while exercise downregulated RPS4X expression. A lowered expression of RPS4X may prolong tumor survival and reduce CRC metastasis. RPS4X and tumor stemness marker-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness both in vitro and in vivo.\nConclusion: RPS4X upregulation may enhance CRC stemness and increase the odds of metastasis. Exercise may reduce CRC metastasis through the regulation of RPS4X.", "claims": [{"id": "claim-method", "statement": "Then, the Kaplan-Meier (KM) method was used to plot the survivorship curves. The log-rank test was used to calculate statistical differences between groups with high and low expression of target mRNA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38439884", "locator": "sections[6] \"Survival prediction of key genes\" paragraph 2", "quote": "Then, the Kaplan-Meier (KM) method was used to plot the survivorship curves. The log-rank test was used to calculate statistical differences between groups with high and low expression of target mRNA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used or analyzed during the present study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38439884", "locator": "sections[30] \"Availability of data and materials\" paragraph 2", "quote": "The datasets used or analyzed during the present study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Exercise may reduce CRC metastasis through the regulation of RPS4X.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38439884", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Exercise may reduce CRC metastasis through the regulation of RPS4X."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Exercise may reduce CRC metastasis through the regulation of RPS4X.", "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:38439884"], "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:GSE157600"], "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:GSE157600"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38439884", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.heliyon.2024.e26604", "sha256": "sha256:e6714a662d42635cf3200881ad235f106e2dacdad6e77ad0087652e56cc1b59e", "bytes": 73251, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.heliyon.2024.e26604", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10909670", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE157600", "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=GSE157600", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE157600", "version": null, "note": "The datasets used or analyzed during the present study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used or analyzed during the present study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4771486", "GSM4771487"], "sample_count": 2, "group_sizes": null, "group_sizes_basis": null, "platform": "17021", "taxon": "Mus musculus", "title": "Single cell transcriptomes of hepatic immune cells from mice with and without colorectal cancer liver metastasis", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE97084", "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=GSE97084", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE97084", "version": null, "note": "The datasets used or analyzed during the present study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used or analyzed during the present study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2551324", "GSM2551325", "GSM2551326", "GSM2551327", "GSM2551328", "GSM2551329", "GSM2551330", "GSM2551331", "GSM2551332", "GSM2551333", "GSM2551334", "GSM2551335", "GSM2551336", "GSM2551337", "GSM2551338", "GSM2551339", "GSM2551340", "GSM2551341", "GSM2551342", "GSM2551343", "GSM2551344", "GSM2551345", "GSM2551346", "GSM2551347", "GSM2551348", "GSM2551349", "GSM2551350", "GSM2551351", "GSM2551352", "GSM2551353", "GSM2551354", "GSM2551355", "GSM2551356", "GSM2551357", "GSM2551358", "GSM2551359", "GSM2551360", "GSM2551361", "GSM2551362", "GSM2551363", "GSM2551364", "GSM2551365", "GSM2551366", "GSM2551367", "GSM2551368", "GSM2551369", "GSM2551370", "GSM2551371", "GSM2551372", "GSM2551373", "GSM2551374", "GSM2551375", "GSM2551376", "GSM2551377", "GSM2551378", "GSM2551379", "GSM2551380", "GSM2551381", "GSM2551382", "GSM2551383", "GSM2551384", "GSM2551385", "GSM2551386", "GSM2551387", "GSM2551388", "GSM2551389", "GSM2551390", "GSM2551391", "GSM2551392", "GSM2551393", "GSM2551394", "GSM2551395", "GSM2551396", "GSM2551397", "GSM2551398", "GSM2551399", "GSM2551400", "GSM2551401", "GSM2551402", "GSM2551403", "GSM2551404", "GSM2551405", "GSM2551406", "GSM2551407", "GSM2551408", "GSM2551409", "GSM2551410", "GSM2551411", "GSM2551412", "GSM2551413", "GSM2551414", "GSM2551415", "GSM2551416", "GSM2551417", "GSM2551418", "GSM2551419", "GSM2551420", "GSM2551421", "GSM2551422", "GSM2551423", "GSM2551424", "GSM2551425", "GSM2551426"], "sample_count": 103, "group_sizes": null, "group_sizes_basis": null, "platform": "11154", "taxon": "Homo sapiens", "title": "Enhanced Protein Translation Underlies Improved Metabolic and Physical Adaptations to Different Exercise Training Modes in Young and Old Humans", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE157600 not downloaded", "asset:data:geo:GSE157600 licence not read", "asset:data:geo:GSE97084 not downloaded", "asset:data:geo:GSE97084 licence not read"]}, "analysis": {"state": "complete", "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": 1.0, "band": "verbatim", "quote": "Then, the Kaplan-Meier (KM) method was used to plot the survivorship curves. 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CRC tumor microarray (TMA) as well as cell/animal experiments are"], "order_basis": "paper_text_order:999", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["r-CD44 were highly positively correlated and knockdown of RPS4X expression reduced tumor stemness b", "free cells were used in all experiments. The transfection process was performed according to protocol", "acquired from RiboBio (Guangzhou, China) and transfection agents. Transcriptome analysis of liver meta", "protocol with 50 nM Small interfering RNAs (siRNA-RPSX4 and siRNA-control) acquired from RiboB"], "order_basis": "paper_text_order:1453", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ion reduced tumor stemness both in vitro and in vivo. Conclusion: RPS4X upregulation may enhance", "ssues Quality control was first performed on mouse liver metastatic cancer tissues from the GSE"], "order_basis": "paper_text_order:1524", "id": "assay:3"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ackage (v3.3.3) in R software (v4.0.3) [44]. RNAseq data were extracted from the TCGA (https://p", "onal pathways Based on a previous study [42] RNAseq data downloaded from the TCGA (https://porta", "ls were used for the downscaling analysis of RNA-seq, to help identify the cluster characteristic", "(Guangzhou, China) and transfection agents. Transcriptome analysis of liver metastatic tumor tissues Q"], "order_basis": "paper_text_order:2032", "id": "assay:4"}, {"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": 1.0, "evidence": ["Then, the Kaplan-Meier (KM) method was used to plot the survivorship curves. The log-rank test was used to calculate statistical differences between groups with high and low expression of target mRNA."], "order_basis": "consumes_earlier_output", "id": "assay:5"}]}