Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33352935", "kind": "science-record", "revision": 7, "content_hash": "sha256:9d2b676af39fd9bdecd6919feb34c1ba3f72616e4a85a6b31777cb45a65c9c20", "created_at": "2026-11-01T15:41:20Z", "updated_at": "2026-11-01T21:24:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Circulating Exosomal MicroRNA-1307-5p as a Predictor for Metastasis in Patients with Hepatocellular Carcinoma.", "doi": "10.3390/cancers12123819", "pmid": "33352935", "authors": ["Jung Woo Eun", "Chul Won Seo", "Geum Ok Baek", "Moon Gyeong Yoon", "Hye Ri Ahn", "Ju A Son", "Suna Sung", "Do Wan Kim", "Soon Sun Kim", "Hyo Jung Cho", "Jae Youn Cheong"], "journal": "Cancers", "year": 2020, "abstract": "Exosomal microRNAs (exo-miRs) contribute to cancer metastasis. To identify pro-metastatic circulating exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients with HCC (eight non-metastatic and six with metastasis within 1 year of follow-up) were analyzed. Sixty-one miRs were significantly overexpressed among patients with metastatic HCC. Candidate miRs were selected through integrative analyses of two different public expression datasets, GSE67140 and The Cancer Genome Atlas liver hepatocellular carcinoma (TCGA_LIHC). Integrative analyses revealed 3 of 61 miRs (miR-106b-5p, miR-1307-5p, and miR-340-5p) commonly overexpressed both in metastasis and vascular invasion groups, with prognostic implications. Validation was performed using stored blood samples of 150 patients with HCC. Validation analysis showed that circulating exo-miR-1307-5p was significantly overexpressed in the metastasis group (p = 0.04), as well as in the vascular invasion and tumor recurrence groups. Circulating exo-miR-1307-5p expression was significantly correlated with tumor stage progression (p < 0.0001). Downstream signaling pathways of miR-1307 were predicted using TargetScan and Ingenuity Pathway Analysis. On comprehensive bioinformatics analysis, the downstream pathway of miR-1307-5p, promoting epithelial-mesenchymal transition (EMT), showed SEC14L2 and ENG downregulation. Our results show that circulating exo-miR-1307-5p promotes metastasis and helps predict metastasis in HCC, and SEC14L2 and ENG are target tumor suppressor genes of miR-1307 that promote EMT.", "claims": [{"id": "claim-data-access", "statement": "To estimate miR expression levels in HCC, public genomic data were obtained from TCGA_LIHC (https://cancergenome.nih.gov) and the GEO database (GSE67140) [16] of the National Center for Biotechnology Information.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33352935", "locator": "sections[10] \"4.2. Analysis of Gene Expression Omnibus (GEO) Database and TCGA_LIHC\" paragraph 2", "quote": "To estimate miR expression levels in HCC, public genomic data were obtained from TCGA_LIHC (https://cancergenome.nih.gov) and the GEO database (GSE67140) [16] of the National Center for Biotechnology Information."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33352935"], "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:GSE67140"], "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:GSE67140"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33352935", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/cancers12123819", "sha256": "sha256:576dff06581ad43fec47abd53b640d42c15ff110328045673e198da14500f4f6", "bytes": 44413, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/cancers12123819", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC7766543", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE67140", "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=GSE67140", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE67140", "version": null, "note": "To estimate miR expression levels in HCC, public genomic data were obtained from TCGA_LIHC (https://cancergenome.nih.gov) and the GEO database (GSE67140) [16] of the National Center for Biotechnology Information.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "To estimate miR expression levels in HCC, public genomic data were obtained from TCGA_LIHC (https://cancergenome.nih.gov) and the GEO database (GSE67140) [16] of the National Center for Biotechnology Information.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1639975", "GSM1639976", "GSM1639977", "GSM1639978", "GSM1639979", "GSM1639980", "GSM1639981", "GSM1639982", "GSM1639983", "GSM1639984", "GSM1639985", "GSM1639986", "GSM1639987", "GSM1639988", "GSM1639989", "GSM1639990", "GSM1639991", "GSM1639992", "GSM1639993", "GSM1639994", "GSM1639995", "GSM1639996", "GSM1639997", "GSM1639998", "GSM1639999", "GSM1640000", "GSM1640001", "GSM1640002", "GSM1640003", "GSM1640004", "GSM1640005", "GSM1640006", "GSM1640007", "GSM1640008", "GSM1640009", "GSM1640010", "GSM1640011", "GSM1640012", "GSM1640013", "GSM1640014", "GSM1640015", "GSM1640016", "GSM1640017", "GSM1640018", "GSM1640019", "GSM1640020", "GSM1640021", "GSM1640022", "GSM1640023", "GSM1640024", "GSM1640025", "GSM1640026", "GSM1640027", "GSM1640028", "GSM1640029", "GSM1640030", "GSM1640031", "GSM1640032", "GSM1640033", "GSM1640034", "GSM1640035", "GSM1640036", "GSM1640037", "GSM1640038", "GSM1640039", "GSM1640040", "GSM1640041", "GSM1640042", "GSM1640043", "GSM1640044", "GSM1640045", "GSM1640046", "GSM1640047", "GSM1640048", "GSM1640049", "GSM1640050", "GSM1640051", "GSM1640052", "GSM1640053", "GSM1640054", "GSM1640055", "GSM1640056", "GSM1640057", "GSM1640058", "GSM1640059", "GSM1640060", "GSM1640061", "GSM1640062", "GSM1640063", "GSM1640064", "GSM1640065", "GSM1640066", "GSM1640067", "GSM1640068", "GSM1640069", "GSM1640070", "GSM1640071", "GSM1640072", "GSM1640073", "GSM1640074", "GSM1640075", "GSM1640076", "GSM1640077", "GSM1640078", "GSM1640079", "GSM1640080", "GSM1640081", "GSM1640082", "GSM1640083", "GSM1640084", "GSM1640085", "GSM1640086", "GSM1640087", "GSM1640088", "GSM1640089", "GSM1640090", "GSM1640091", "GSM1640092", "GSM1640093", "GSM1640094", "GSM1640095", "GSM1640096", "GSM1640097", "GSM1640098", "GSM1640099", "GSM1640100", "GSM1640101", "GSM1640102", "GSM1640103", "GSM1640104", "GSM1640105", "GSM1640106", "GSM1640107", "GSM1640108", "GSM1640109", "GSM1640110", "GSM1640111", "GSM1640112", "GSM1640113", "GSM1640114", "GSM1640115", "GSM1640116", "GSM1640117", "GSM1640118", "GSM1640119", "GSM1640120", "GSM1640121", "GSM1640122", "GSM1640123", "GSM1640124", "GSM1640125", "GSM1640126", "GSM1640127", "GSM1640128", "GSM1640129", "GSM1640130", "GSM1640131", "GSM1640132", "GSM1640133", "GSM1640134", "GSM1640135", "GSM1640136", "GSM1640137", "GSM1640138", "GSM1640139", "GSM1640140", "GSM1640141", "GSM1640142", "GSM1640143", "GSM1640144", "GSM1640145", "GSM1640146", "GSM1640147", "GSM1640148", "GSM1640149", "GSM1640150", "GSM1640151"], "sample_count": 177, "group_sizes": null, "group_sizes_basis": null, "platform": "8786", "taxon": "Homo sapiens; synthetic construct", "title": "Identification of differentially expressed microRNAs between human HCC tumors with and without vascular invasion", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33352935:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:f1b6b9d54f0c7053776946a592178b59b29896b7d0e6a038da3fb9ee7d237ef4", "bytes": 1280, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[9]/table-wrap[1]#cancers-12-03819-t001", "version": null, "note": "Baseline characteristics of the Plasma-HCC cohort and the Serum-HCC cohort.", "structure": {"pmcid": "PMC7766543", "section_index": 9, "section_title": "4.1. Patients and Sample Collection", "row_count": 18, "column_count": 4}, "table": {"label": "Table 1", "caption": "Baseline characteristics of the Plasma-HCC cohort and the Serum-HCC cohort.", "rows": [["Variables", "Plasma-HCC Cohort (n = 52)", "Serum-HCC Cohort (n = 91)"], ["HCC (n = 52)", "Healthy Control(n = 28)", "HCC (n = 73)"], ["Age (years), mean ± SD", "54.22 ± 9.98", "34.96 ± 8.18", "54.62 ± 9.06"], ["Male sex, n (%)", "47 (85.5)", "3 (10.7)", "57 (78.1)"], ["AST, IU/mL", "72.73 ± 77.36", "16.82 ± 4.06", "73.81 ± 92.28"], ["ALT, IU/mL", "46.11 ± 32.85", "14.14 ± 7.77", "49.48 ± 63.53"], ["Platelet, x109/L", "161.59 ± 82.04", "314± 63.33", "169.85 ± 85.41"], ["AFP (ng/mL), mean ± SD", "8000.26 ± 17,325.08", "1.65 ± 0.58", "4394.77 ± 14,600.73"], ["Etiology, nHBV/HCV/alcohol/others", "–", "", "65/4/3/1"], ["Albumin (g/L), mean ± SD", "4.07 ± 0.60", "", "4.23 ± 0.55"], ["Bilirubin (mg/dL), mean ± SD", "1.22 ± 1.81", "", "1.49 ± 3.91"], ["INR, mean ± SD", "1.16 ± 0.14", "", "1.18 ± 0.19"], ["Modified UICC stage, n (%)", "–", "", "26 (36)/9 (12)/20 (27)/11 (15.4)/7 (9.6)"], ["I/II/III/IVa/IVb"], ["Metastasis, n (%)", "25 (48.1)/27 (51.9)", "7 (9.6)/66 (90.4)"], ["Yes/No"], ["Vascular invasion, n (%)", "–", "29 (54.7)/24 (45.3)"], ["Yes/No"]], "row_count": 18, "column_count": 4, "numeric_cells": 35, "header_rows": 2, "locator": "section[9]/table-wrap[1]#cancers-12-03819-t001"}}], "gaps": ["asset:data:geo:GSE67140 not downloaded", "asset:data:geo:GSE67140 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "welch_t_test", "label": "Group comparison", "dsl_operations": ["welch_t"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Welch"}}, {"id": "method-2", "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": []}, "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": ["welch_t"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: welch_t_test."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["welch_t"], "assets": ["source:pmid:33352935", "data:geo:GSE67140", "asset:table:pmid:33352935:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE67140"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T19:19:47Z", "independence": "single_reader"}, "evidence_check": {"method": "absent", "availability": null}, "calls": 3, "usage": {"prompt_tokens": 36883, "completion_tokens": 2030, "cached_tokens": 784}}, "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:33352935", "type": "paper", "label": "pmid:33352935"}, {"id": "source:pmid:33352935", "type": "manuscript", "label": "PMID 33352935 full text"}, {"id": "data:geo:GSE67140", "type": "dataset", "label": "GEO GSE67140"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33352935", "type": "paper", "label": "pmid:33352935"}, {"id": "source:pmid:33352935", "type": "manuscript", "label": "PMID 33352935 full text"}, {"id": "data:geo:GSE67140", "type": "dataset", "label": "GEO GSE67140"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33352935", "type": "extraction", "used": ["source:pmid:33352935"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE67140", "type": "accession_resolution", "used": ["data:geo:GSE67140"], "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:33352935", "parent_hash": "sha256:23d6cc24ec6330607ffbe2c1a00a35aceb33b0f02a535b1e57b7c8eab8c8ca52", "fork_of": null, "generation": 6}, "gaps": ["asset:data:geo:GSE67140 licence not read", "asset:data:geo:GSE67140 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "amplicon_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["exo-miRs in hepatocellular carcinoma (HCC), next-generation sequencing-based plasma exo-miR profiles of 14 patients"], "order_basis": "paper_text_order:213", "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": 0.99, "evidence": ["ngly enriched in the samples. The results of western blotting showed that the isolated vesicles were posit", "tribution and concentration of exosomes. (c) Western blot analysis. Plasma exosomes were positive for"], "order_basis": "paper_text_order:2433", "id": "assay:2"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["somal RNA was appropriately extracted. Small RNA sequencing libraries were successfully generated from 1"], "order_basis": "paper_text_order:2749", "id": "assay:3"}, {"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": ["mation. 4.3. Cell Culture and AS-miR-1307-5p Transfection Hep3B and Huh-7 cells (ATCC, Manassas, VA, U", "ense inhibitor (Bioneer, Daejeon, Korea) was transfected into Huh7 cells using Lipofectamine 2000 (In"], "order_basis": "paper_text_order:6869", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["d Huh-7 cells (ATCC, Manassas, VA, USA) were cultured in EMEM or DMEM mudium (GenDEPOT, Barker, TX, U"], "order_basis": "paper_text_order:6935", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["welch_t"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Welch"], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}