{"id":"https://openalex.org/W7171470103","doi":"https://doi.org/10.3390/ijms27156643","title":"Deciphering the Leading-Edge Spatiotemporal Microenvironment of Hepatocellular Carcinoma for Targeted Drug Discovery Using SpaPred","display_name":"Deciphering the Leading-Edge Spatiotemporal Microenvironment of Hepatocellular Carcinoma for Targeted Drug Discovery Using SpaPred","publication_year":2026,"publication_date":"2026-07-25","ids":{"openalex":"https://openalex.org/W7171470103","doi":"https://doi.org/10.3390/ijms27156643","pmid":"https://pubmed.ncbi.nlm.nih.gov/42589301","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13466823"},"language":"en","primary_location":{"id":"doi:10.3390/ijms27156643","doi":"https://doi.org/10.3390/ijms27156643","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms27156643","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3390/ijms27156643","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5111103067","display_name":"S Zhang","orcid":"https://orcid.org/0009-0000-3653-0503","observed_orcids":["https://orcid.org/0009-0000-3653-0503"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Shibo Zhang","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":"https://orcid.org/0009-0000-3653-0503","affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034945782","display_name":"Ziqiao Li","orcid":"https://orcid.org/0000-0001-8772-6792","observed_orcids":["https://orcid.org/0000-0001-8772-6792"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Ziqiao Li","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5143738290","display_name":"Kexin Yu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Kexin Yu","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5143708652","display_name":"Guang Shi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Guang Shi","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112961246","display_name":"Yangguang Su","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Yangguang Su","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100602790","display_name":"Xin Hu","orcid":"https://orcid.org/0000-0003-2800-3492","observed_orcids":["https://orcid.org/0000-0003-2800-3492"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xin Hu","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5055745143","display_name":"Xiujie Chen","orcid":"https://orcid.org/0000-0003-2423-8569","observed_orcids":["https://orcid.org/0000-0003-2423-8569"]},"institutions":[{"id":"https://openalex.org/I156144747","display_name":"Harbin Medical University","ror":"https://ror.org/05jscf583","country_code":"CN","type":"education","lineage":["https://openalex.org/I156144747"]}],"countries":["CN"],"is_corresponding":true,"raw_author_name":"Xiujie Chen","raw_affiliation_strings":["College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China"],"raw_orcid":"https://orcid.org/0000-0003-2423-8569","affiliations":[{"raw_affiliation_string":"College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China","institution_ids":["https://openalex.org/I156144747"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5055745143"],"corresponding_institution_ids":["https://openalex.org/I156144747"],"apc_list":{"value":2900,"currency":"CHF","value_usd":3499},"apc_paid":{"value":2900,"currency":"CHF","value_usd":3499},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.42158674,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"27","issue":"15","first_page":"6643","last_page":"6643"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.8223000168800354,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T11289","display_name":"Single-cell and spatial transcriptomics","score":0.8223000168800354,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10073","display_name":"Hepatocellular Carcinoma Treatment and Prognosis","score":0.05570000037550926,"subfield":{"id":"https://openalex.org/subfields/2721","display_name":"Hepatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.02459999918937683,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hepatocellular-carcinoma","display_name":"hepatocellular carcinoma","score":0.9980000257492065},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.7870000004768372},{"id":"https://openalex.org/keywords/sparc","display_name":"SPARC","score":0.6359999775886536},{"id":"https://openalex.org/keywords/igfbp7","display_name":"IGFBP7","score":1.0},{"id":"https://openalex.org/keywords/stromal-remodeling","display_name":"stromal remodeling","score":0.8769999742507935},{"id":"https://openalex.org/keywords/immune-depletion","display_name":"immune depletion","score":0.7039999961853027},{"id":"https://openalex.org/keywords/intratumor-heterogeneity","display_name":"intratumoral heterogeneity","score":0.9049999713897705},{"id":"https://openalex.org/keywords/intercellular-communication","display_name":"intercellular communication","score":0.8019999861717224},{"id":"https://openalex.org/keywords/trajectory-perturbation","display_name":"trajectory perturbation","score":0.6690000295639038},{"id":"https://openalex.org/keywords/drug-target-identification","display_name":"drug target identification","score":0.46299999952316284},{"id":"https://openalex.org/keywords/oxaliplatin","display_name":"oxaliplatin","score":0.8949999809265137},{"id":"https://openalex.org/keywords/belinostat","display_name":"belinostat","score":0.9990000128746033},{"id":"https://openalex.org/keywords/temsirolimus","display_name":"temsirolimus","score":1.0}],"concepts":[{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.7955999970436096},{"id":"https://openalex.org/C2778019345","wikidata":"https://www.wikidata.org/wiki/Q1148337","display_name":"Hepatocellular carcinoma","level":2,"score":0.765999972820282},{"id":"https://openalex.org/C74187038","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug discovery","level":2,"score":0.6710000038146973},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.6226999759674072},{"id":"https://openalex.org/C16930146","wikidata":"https://www.wikidata.org/wiki/Q4381253","display_name":"Stromal cell","level":2,"score":0.5546000003814697},{"id":"https://openalex.org/C170734499","wikidata":"https://www.wikidata.org/wiki/Q1152227","display_name":"Pharmacogenomics","level":2,"score":0.5152999758720398},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5077000260353088},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.45680001378059387},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.39899998903274536},{"id":"https://openalex.org/C2776820818","wikidata":"https://www.wikidata.org/wiki/Q7699074","display_name":"Temsirolimus","level":5,"score":0.36629998683929443},{"id":"https://openalex.org/C152662350","wikidata":"https://www.wikidata.org/wiki/Q815297","display_name":"Systems biology","level":2,"score":0.35269999504089355},{"id":"https://openalex.org/C69991583","wikidata":"https://www.wikidata.org/wiki/Q1423575","display_name":"Candidate gene","level":3,"score":0.33550000190734863},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.30489999055862427},{"id":"https://openalex.org/C163763905","wikidata":"https://www.wikidata.org/wiki/Q17075943","display_name":"Precision medicine","level":2,"score":0.29980000853538513},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.28040000796318054},{"id":"https://openalex.org/C193244246","wikidata":"https://www.wikidata.org/wiki/Q5432696","display_name":"False discovery rate","level":3,"score":0.27469998598098755},{"id":"https://openalex.org/C52124034","wikidata":"https://www.wikidata.org/wiki/Q557179","display_name":"Stroma","level":3,"score":0.260699987411499},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.25699999928474426},{"id":"https://openalex.org/C3019038264","wikidata":"https://www.wikidata.org/wiki/Q1418791","display_name":"Drug candidate","level":3,"score":0.25049999356269836}],"mesh":[{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D006528","descriptor_name":"Carcinoma, Hepatocellular","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D006528","descriptor_name":"Carcinoma, Hepatocellular","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D006528","descriptor_name":"Carcinoma, Hepatocellular","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006528","descriptor_name":"Carcinoma, Hepatocellular","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D008113","descriptor_name":"Liver Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D015972","descriptor_name":"Gene Expression Regulation, Neoplastic","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D055808","descriptor_name":"Drug Discovery","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":true},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true}],"locations_count":3,"locations":[{"id":"doi:10.3390/ijms27156643","doi":"https://doi.org/10.3390/ijms27156643","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms27156643","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},{"id":"pmid:42589301","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42589301","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International journal of molecular sciences","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13466823","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13466823/","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Int J Mol Sci","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.3390/ijms27156643","doi":"https://doi.org/10.3390/ijms27156643","is_oa":true,"landing_page_url":"https://doi.org/10.3390/ijms27156643","pdf_url":null,"source":{"id":"https://openalex.org/S10623703","display_name":"International Journal of Molecular Sciences","issn_l":"1422-0067","issn":["1422-0067","1661-6596"],"is_oa":true,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","medline","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310310987","host_organization_name":"Multidisciplinary Digital Publishing Institute","host_organization_lineage":["https://openalex.org/P4310310987"],"host_organization_lineage_names":["Multidisciplinary Digital Publishing Institute"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"International Journal of Molecular Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":57,"referenced_works":["https://openalex.org/W1792532087","https://openalex.org/W2047039797","https://openalex.org/W2117990720","https://openalex.org/W2122731269","https://openalex.org/W2145578524","https://openalex.org/W2149031002","https://openalex.org/W2162065265","https://openalex.org/W2167597760","https://openalex.org/W2261944919","https://openalex.org/W2341128841","https://openalex.org/W2766437506","https://openalex.org/W2984472267","https://openalex.org/W3016360824","https://openalex.org/W3047141442","https://openalex.org/W3090990034","https://openalex.org/W3095901950","https://openalex.org/W3127422037","https://openalex.org/W3129476455","https://openalex.org/W3131460561","https://openalex.org/W3134482219","https://openalex.org/W3135107870","https://openalex.org/W3171648992","https://openalex.org/W3182293965","https://openalex.org/W3190202966","https://openalex.org/W3197944718","https://openalex.org/W3208940117","https://openalex.org/W3212775964","https://openalex.org/W4200307603","https://openalex.org/W4205498896","https://openalex.org/W4205817967","https://openalex.org/W4210575300","https://openalex.org/W4221045277","https://openalex.org/W4224221174","https://openalex.org/W4225272983","https://openalex.org/W4283328362","https://openalex.org/W4285200430","https://openalex.org/W4294216483","https://openalex.org/W4298009402","https://openalex.org/W4307468223","https://openalex.org/W4323036511","https://openalex.org/W4376867947","https://openalex.org/W4378212544","https://openalex.org/W4381249426","https://openalex.org/W4385987383","https://openalex.org/W4386034505","https://openalex.org/W4388455891","https://openalex.org/W4388615774","https://openalex.org/W4388615780","https://openalex.org/W4389348675","https://openalex.org/W4392683670","https://openalex.org/W4396738984","https://openalex.org/W4400578706","https://openalex.org/W4402604581","https://openalex.org/W4403284571","https://openalex.org/W4403810280","https://openalex.org/W4416719943","https://openalex.org/W7119489890"],"related_works":["https://openalex.org/W7128702036","https://openalex.org/W7171286345","https://openalex.org/W4416088127","https://openalex.org/W7126186848","https://openalex.org/W7214638939","https://openalex.org/W4285200430","https://openalex.org/W7154086899","https://openalex.org/W4413297834","https://openalex.org/W4399597232","https://openalex.org/W7164341993"],"abstract_inverted_index":{"The":[0],"leading-edge":[1],"(LE)":[2],"of":[3,31,81,92,99,105],"hepatocellular":[4],"carcinoma":[5],"(HCC)":[6],"is":[7,15],"a":[8,138],"critical":[9],"region":[10],"driving":[11],"malignant":[12],"progression":[13],"and":[14,22,33,47,53,64,109,116,131,145],"closely":[16],"associated":[17,41,121],"with":[18,42,122],"high":[19],"patient":[20],"mortality":[21],"marked":[23],"intratumoral":[24],"heterogeneity.":[25],"Multi-omics":[26],"integration":[27,104],"identified":[28],"elevated":[29],"expression":[30],"SPARC":[32],"IGFBP7":[34],"in":[35,76,95,106,149],"the":[36,78,84,90,97],"LE":[37],"region,":[38],"which":[39,72],"was":[40],"stromal":[43,62],"remodeling-related":[44],"transcriptional":[45,124],"programs":[46],"an":[48],"immune-depleted":[49],"microenvironment.":[50],"Cell-cell":[51],"communication":[52],"pathway":[54],"analyses":[55,112],"further":[56],"suggested":[57],"potential":[58],"links":[59],"between":[60],"LE-associated":[61],"states":[63],"pro-invasive":[65],"signaling":[66],"programs.":[67,125],"Furthermore,":[68],"we":[69],"developed":[70],"SpaPred,":[71],"demonstrated":[73],"favorable":[74],"performance":[75],"inferring":[77],"spatiotemporal":[79],"heterogeneity":[80,144],"HCC":[82],"at":[83],"spatial":[85,101,143],"resolution.":[86],"This":[87],"model":[88],"overcomes":[89],"limitations":[91],"existing":[93],"algorithms":[94],"analyzing":[96],"composition":[98],"tissue":[100],"structures.":[102],"Finally,":[103],"silico":[107],"trajectory-perturbation":[108],"pharmacogenomic":[110],"drug-response":[111],"prioritized":[113],"Oxaliplatin,":[114],"Belinostat,":[115],"Temsirolimus":[117],"as":[118],"candidate":[119,146],"compounds":[120],"LE-related":[123],"These":[126],"drug":[127],"predictions":[128],"are":[129],"computational":[130],"require":[132],"experimental":[133],"validation.":[134],"Collectively,":[135],"SpaPred":[136],"provides":[137],"hypothesis-generating":[139],"framework":[140],"for":[141],"investigating":[142],"therapeutic":[147],"vulnerabilities":[148],"HCC.":[150]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2026-07-28T00:00:00"}
