Identification of a Solute Carrier Family-Based Signature for Predicting Overall Survival in Osteosarcoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35518353", "kind": "science-record", "revision": 4, "content_hash": "sha256:30c60fd5e3f5984611aead9fb924c05413a794bedfc32049c1637b9d4c261fc9", "created_at": "2026-11-01T18:14:24Z", "updated_at": "2026-11-01T22:06:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of a Solute Carrier Family-Based Signature for Predicting Overall Survival in Osteosarcoma.", "doi": "10.3389/fgene.2022.849789", "pmid": "35518353", "authors": ["Di Zheng", "Zhun Wei", "Weichun Guo"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Given the important role of SLC family in essential physiological processes including nutrient uptake, ion transport, and waste removal, and that their dysregulation was found in distinct forms of cancer, here we identified a novel gene signature of SLC family for patient risk stratification in osteosarcoma. Gene expression data and relevant clinical materials of osteosarcoma samples were retrieved from The Cancer Genome Atlas (TCGA) database. Prognosis-related SLC genes were identified by performing univariate Cox regression analysis and were utilized to construct a four-SLC gene signature in osteosarcoma. It allowed patients to be classified into high- and low-risk groups, and Kaplan-Meier survival analysis in the training, testing, entire, and external GSE21257 cohorts suggested that the overall survival of patients in high-risk group was consistently worse than that in low-risk group, suggesting the promising accuracy and generalizability of the SLC-based signature in predicting the prognosis of patients with osteosarcoma. Moreover, univariate and multivariate Cox regression analyses indicated that the derived risk score was the only independent prognostic factor for osteosarcoma patients in TCGA and GSE21257 cohorts. Besides, a prognostic nomogram comprising the derived risk score and clinical features including gender and age was developed for clinical decision-making. Functional enrichment analyses of the differentially expressed genes between high- and low-risk group revealed that immune-related biological processes and pathways were significantly enriched. Estimation of tumor immune microenvironment using ESTIMATE algorithm revealed that patients with lower risk score had higher stromal, immune, and ESTIMATE score, and lower tumor purity. ssGSEA analyses indicated that the scores of various immune subpopulations including CD8+ T cells, DCs, and TIL were lower in high-risk group than these in low-risk group in both cohorts. As for the related immune functions, the scores of APC co-inhibition, CCR, check-point, T cell co-stimulation, and Type II IFN response were lower in high-risk group than these in low-risk group in both cohorts. In all, we identified a novel prognostic signature based on four SLC family genes that accurately predicted overall survival in osteosarcoma patients. Furthermore, the signature is linked to differences in immunological status and immune cell infiltrations in the tumor microenvironment.", "claims": [{"id": "claim-method", "statement": "These SLC genes were subjected to univariate Cox regression analysis after being assigned in a uniform nomenclature in both the TCGA osteosarcoma dataset and the GSE21257 dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35518353", "locator": "sections[4] \"Identification of Prognosis-Related SLC Genes\" paragraph 2", "quote": "These SLC genes were subjected to univariate Cox regression analysis after being assigned in a uniform nomenclature in both the TCGA osteosarcoma dataset and the GSE21257 dataset."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35518353", "locator": "sections[22] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We used univariate Cox regression analysis on datasets from the TCGA database to discover prognosis-related genes of the SLC family in osteosarcoma.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35518353", "locator": "sections[11] \"Identification of Prognosis-Related Genes in SLC Family\" paragraph 2", "quote": "We used univariate Cox regression analysis on datasets from the TCGA database to discover prognosis-related genes of the SLC family in osteosarcoma."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We used univariate Cox regression analysis on datasets from the TCGA database to discover prognosis-related genes of the SLC family in osteosarcoma.", "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:35518353"], "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:GSE21257"], "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:GSE21257"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35518353", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.849789", "sha256": "sha256:b66dda2eafcabcf1c1bafc55d13090005275b0eebf1b86fc6458e85e44b958be", "bytes": 41156, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2022.849789", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9061960", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE21257", "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=GSE21257", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE21257", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM530667", "GSM530899", "GSM531283", "GSM531284", "GSM531285", "GSM531286", "GSM531287", "GSM531288", "GSM531289", "GSM531290", "GSM531291", "GSM531292", "GSM531293", "GSM531294", "GSM531295", "GSM531296", "GSM531297", "GSM531298", "GSM531299", "GSM531300", "GSM531301", "GSM531302", "GSM531303", "GSM531304", "GSM531305", "GSM531306", "GSM531307", "GSM531308", "GSM531309", "GSM531310", "GSM531311", "GSM531312", "GSM531313", "GSM531314", "GSM531319", "GSM531320", "GSM531321", "GSM531322", "GSM531323", "GSM531324", "GSM531325", "GSM531326", "GSM531327", "GSM531328", "GSM531329", "GSM531330", "GSM531331", "GSM531332", "GSM531333", "GSM531334", "GSM531335", "GSM531351", "GSM531352"], "sample_count": 53, "group_sizes": null, "group_sizes_basis": null, "platform": "10295", "taxon": "Homo sapiens", "title": "Genome-wide gene expression profiling on pre-chemotherapy biopsies of osteosarcoma patients who developed metastases within 5yrs (n=34) and patients who did not develop metastases within 5yrs (n=19)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE21257 not downloaded", "asset:data:geo:GSE21257 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "These SLC genes were subjected to univariate Cox regression analysis after being assigned in a uniform nomenclature in both the TCGA osteosarcoma dataset and the GSE21257 dataset."}}, {"id": "method-2", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-3", "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-4", "family": "survival_analysis", "specific": "log_rank_test", "label": "Survival analysis", "dsl_operations": ["logrank_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.8, "band": "high", "quote": "log-rank"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "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": ["GSE21257"], "resolved_accessions": ["GSE21257"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE21257 in Gene Expression Omnibus and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35518353", "data:geo:GSE21257"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE21257"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:44:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11144, "completion_tokens": 1434, "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:35518353", "type": "paper", "label": "pmid:35518353"}, {"id": "source:pmid:35518353", "type": "manuscript", "label": "PMID 35518353 full text"}, {"id": "data:geo:GSE21257", "type": "dataset", "label": "GEO GSE21257"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35518353", "type": "paper", "label": "pmid:35518353"}, {"id": "source:pmid:35518353", "type": "manuscript", "label": "PMID 35518353 full text"}, {"id": "data:geo:GSE21257", "type": "dataset", "label": "GEO GSE21257"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35518353", "type": "extraction", "used": ["source:pmid:35518353"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE21257", "type": "accession_resolution", "used": ["data:geo:GSE21257"], "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:35518353", "parent_hash": "sha256:f2d28d2ef2f9e3feca73e4cd5f049d802474940a738f049bd588443f49eb7b28", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE21257 licence not read", "asset:data:geo:GSE21257 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["These SLC genes were subjected to univariate Cox regression analysis after being assigned in a uniform nomenclature in both the TCGA osteosarcoma dataset and the GSE21257 dataset."], "order_basis": "analysis_only", "id": "assay:1"}]}