{"id":"https://openalex.org/W4414524046","doi":"https://doi.org/10.3389/fbinf.2025.1664576","title":"Integrative machine learning and transcriptomic analysis identifies key molecular targets in MNPN-associated oral squamous cell carcinoma pathogenesis","display_name":"Integrative machine learning and transcriptomic analysis identifies key molecular targets in MNPN-associated oral squamous cell carcinoma pathogenesis","publication_year":2025,"publication_date":"2025-09-25","ids":{"openalex":"https://openalex.org/W4414524046","doi":"https://doi.org/10.3389/fbinf.2025.1664576","pmid":"https://pubmed.ncbi.nlm.nih.gov/41078533"},"language":"en","primary_location":{"id":"doi:10.3389/fbinf.2025.1664576","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fbinf.2025.1664576","pdf_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2025.1664576/pdf","source":{"id":"https://openalex.org/S4210219554","display_name":"Frontiers in Bioinformatics","issn_l":"2673-7647","issn":["2673-7647"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Bioinformatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2025.1664576/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5115601882","display_name":"Xiangjun Wang","orcid":"https://orcid.org/0000-0001-6519-7893"},"institutions":[{"id":"https://openalex.org/I4210144384","display_name":"Third Affiliated Hospital of Zhengzhou University","ror":"https://ror.org/039nw9e11","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210144384"]},{"id":"https://openalex.org/I4210149496","display_name":"Zhengzhou People's Hospital","ror":"https://ror.org/04tgrpw60","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210149496"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Xiangjun Wang","raw_affiliation_strings":["Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China","institution_ids":["https://openalex.org/I4210149496","https://openalex.org/I4210144384"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060925226","display_name":"Panpan Jin","orcid":null},"institutions":[{"id":"https://openalex.org/I4210144384","display_name":"Third Affiliated Hospital of Zhengzhou University","ror":"https://ror.org/039nw9e11","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210144384"]},{"id":"https://openalex.org/I4210149496","display_name":"Zhengzhou People's Hospital","ror":"https://ror.org/04tgrpw60","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210149496"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Panpan Jin","raw_affiliation_strings":["Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China","institution_ids":["https://openalex.org/I4210149496","https://openalex.org/I4210144384"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5102000587","display_name":"Juan Xu","orcid":"https://orcid.org/0000-0002-6486-0128"},"institutions":[{"id":"https://openalex.org/I4210144384","display_name":"Third Affiliated Hospital of Zhengzhou University","ror":"https://ror.org/039nw9e11","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210144384"]},{"id":"https://openalex.org/I4210149496","display_name":"Zhengzhou People's Hospital","ror":"https://ror.org/04tgrpw60","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210149496"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Juan Xu","raw_affiliation_strings":["Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China","institution_ids":["https://openalex.org/I4210149496","https://openalex.org/I4210144384"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100363197","display_name":"Junyi Li","orcid":"https://orcid.org/0000-0001-5410-9798"},"institutions":[{"id":"https://openalex.org/I4210144384","display_name":"Third Affiliated Hospital of Zhengzhou University","ror":"https://ror.org/039nw9e11","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210144384"]},{"id":"https://openalex.org/I4210149496","display_name":"Zhengzhou People's Hospital","ror":"https://ror.org/04tgrpw60","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210149496"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Junyi Li","raw_affiliation_strings":["Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China","institution_ids":["https://openalex.org/I4210149496","https://openalex.org/I4210144384"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5034930746","display_name":"Mingfang Ji","orcid":"https://orcid.org/0000-0003-4727-2858"},"institutions":[{"id":"https://openalex.org/I4210144384","display_name":"Third Affiliated Hospital of Zhengzhou University","ror":"https://ror.org/039nw9e11","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210144384"]},{"id":"https://openalex.org/I4210149496","display_name":"Zhengzhou People's Hospital","ror":"https://ror.org/04tgrpw60","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210149496"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Mengzhen Ji","raw_affiliation_strings":["Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Stomatology, The Third People's Hospital of Henan Province, Zhengzhou, China","institution_ids":["https://openalex.org/I4210149496","https://openalex.org/I4210144384"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":1900,"currency":"USD","value_usd":1900},"apc_paid":{"value":1900,"currency":"USD","value_usd":1900},"fwci":0.8404,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":{"value":0.75711337,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":94,"max":97},"biblio":{"volume":"5","issue":null,"first_page":"1664576","last_page":"1664576"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11452","display_name":"Oral Health Pathology and Treatment","score":0.9002000093460083,"subfield":{"id":"https://openalex.org/subfields/3506","display_name":"Periodontics"},"field":{"id":"https://openalex.org/fields/35","display_name":"Dentistry"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T11452","display_name":"Oral Health Pathology and Treatment","score":0.9002000093460083,"subfield":{"id":"https://openalex.org/subfields/3506","display_name":"Periodontics"},"field":{"id":"https://openalex.org/fields/35","display_name":"Dentistry"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10307","display_name":"Head and Neck Cancer Studies","score":0.028699999675154686,"subfield":{"id":"https://openalex.org/subfields/2733","display_name":"Otorhinolaryngology"},"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/T13328","display_name":"Osteomyelitis and Bone Disorders Research","score":0.006200000178068876,"subfield":{"id":"https://openalex.org/subfields/2745","display_name":"Rheumatology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/transcriptome","display_name":"Transcriptome","score":0.6549000144004822},{"id":"https://openalex.org/keywords/key","display_name":"Key (lock)","score":0.4499000012874603},{"id":"https://openalex.org/keywords/oral-cancers","display_name":"Oral Cancers","score":0.3700999915599823},{"id":"https://openalex.org/keywords/cancer","display_name":"Cancer","score":0.3682999908924103},{"id":"https://openalex.org/keywords/pathogenesis","display_name":"Pathogenesis","score":0.3456000089645386},{"id":"https://openalex.org/keywords/basal-cell","display_name":"Basal cell","score":0.3416000008583069}],"concepts":[{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.6549000144004822},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4982999861240387},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4943000078201294},{"id":"https://openalex.org/C26517878","wikidata":"https://www.wikidata.org/wiki/Q228039","display_name":"Key (lock)","level":2,"score":0.4499000012874603},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.4392000138759613},{"id":"https://openalex.org/C2909289247","wikidata":"https://www.wikidata.org/wiki/Q1143025","display_name":"Oral Cancers","level":3,"score":0.3700999915599823},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3682999908924103},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3465000092983246},{"id":"https://openalex.org/C2780942790","wikidata":"https://www.wikidata.org/wiki/Q372016","display_name":"Pathogenesis","level":2,"score":0.3456000089645386},{"id":"https://openalex.org/C3019992690","wikidata":"https://www.wikidata.org/wiki/Q92767510","display_name":"Basal cell","level":2,"score":0.3416000008583069},{"id":"https://openalex.org/C2777417228","wikidata":"https://www.wikidata.org/wiki/Q159532","display_name":"Betel","level":3,"score":0.3264999985694885},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3253999948501587},{"id":"https://openalex.org/C27415008","wikidata":"https://www.wikidata.org/wiki/Q7256382","display_name":"Psychological intervention","level":2,"score":0.31470000743865967},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.30480000376701355},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.28700000047683716},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.28619998693466187},{"id":"https://openalex.org/C2779473830","wikidata":"https://www.wikidata.org/wiki/Q1540899","display_name":"MEDLINE","level":2,"score":0.26499998569488525},{"id":"https://openalex.org/C2994491419","wikidata":"https://www.wikidata.org/wiki/Q681817","display_name":"Squamous carcinoma","level":3,"score":0.25540000200271606},{"id":"https://openalex.org/C2781197716","wikidata":"https://www.wikidata.org/wiki/Q864574","display_name":"Biomarker","level":2,"score":0.25049999356269836}],"mesh":[],"locations_count":5,"locations":[{"id":"doi:10.3389/fbinf.2025.1664576","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fbinf.2025.1664576","pdf_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2025.1664576/pdf","source":{"id":"https://openalex.org/S4210219554","display_name":"Frontiers in Bioinformatics","issn_l":"2673-7647","issn":["2673-7647"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Bioinformatics","raw_type":"journal-article"},{"id":"pmid:41078533","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/41078533","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,"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":"Frontiers in bioinformatics","raw_type":null},{"id":"pmh:oai:doaj.org/article:a5c08c7235104a48914fe1f669eea149","is_oa":true,"landing_page_url":"https://doaj.org/article/a5c08c7235104a48914fe1f669eea149","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Bioinformatics, Vol 5 (2025)","raw_type":"article"},{"id":"pmh:oai:europepmc.org:11316651","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12508658","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Text"},{"id":"pmh:oai:pubmedcentral.nih.gov:12508658","is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12508658/","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,"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":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Front Bioinform","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.3389/fbinf.2025.1664576","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fbinf.2025.1664576","pdf_url":"https://www.frontiersin.org/journals/bioinformatics/articles/10.3389/fbinf.2025.1664576/pdf","source":{"id":"https://openalex.org/S4210219554","display_name":"Frontiers in Bioinformatics","issn_l":"2673-7647","issn":["2673-7647"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Bioinformatics","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":false},"content_urls":{"pdf":"https://content.openalex.org/works/W4414524046.pdf"},"referenced_works_count":39,"referenced_works":["https://openalex.org/W1769945967","https://openalex.org/W1966327575","https://openalex.org/W2049367548","https://openalex.org/W2105271269","https://openalex.org/W2178941970","https://openalex.org/W2535385744","https://openalex.org/W2611425558","https://openalex.org/W2771871673","https://openalex.org/W2808438085","https://openalex.org/W2900090807","https://openalex.org/W2946412700","https://openalex.org/W2964310597","https://openalex.org/W2993607662","https://openalex.org/W3006128298","https://openalex.org/W3040837018","https://openalex.org/W3078821236","https://openalex.org/W3119664087","https://openalex.org/W3133891086","https://openalex.org/W3160142016","https://openalex.org/W3175752499","https://openalex.org/W3181803118","https://openalex.org/W3215506708","https://openalex.org/W4220686525","https://openalex.org/W4224260803","https://openalex.org/W4224322506","https://openalex.org/W4225291803","https://openalex.org/W4294946085","https://openalex.org/W4311325417","https://openalex.org/W4313472226","https://openalex.org/W4321167021","https://openalex.org/W4366988971","https://openalex.org/W4385296079","https://openalex.org/W4386945111","https://openalex.org/W4389311505","https://openalex.org/W4391917487","https://openalex.org/W4392383819","https://openalex.org/W4395082424","https://openalex.org/W4403845965","https://openalex.org/W4406278107"],"related_works":[],"abstract_inverted_index":{"Background:":[0],"Oral":[1],"squamous":[2],"cell":[3],"carcinoma":[4],"(OSCC)":[5],"represents":[6],"a":[7,17,23,31,47,196,207],"significant":[8],"global":[9],"health":[10],"challenge,":[11],"with":[12,100,128,140,200],"betel":[13,24,214],"nut":[14,215],"consumption":[15],"being":[16],"major":[18],"risk":[19],"factor.":[20],"3-(methylnitrosamino)propionitrile":[21],"(MNPN),":[22],"nut-derived":[25],"nitrosamine,":[26],"has":[27],"been":[28],"identified":[29,113,136],"as":[30,156,195],"potential":[32,115],"carcinogen,":[33],"but":[34],"its":[35],"molecular":[36,187],"targets":[37,78,117],"in":[38,171,227],"OSCC":[39,67,191],"pathogenesis":[40],"remain":[41],"poorly":[42],"understood.":[43],"Methods:":[44],"We":[45],"employed":[46],"comprehensive":[48,186],"computational":[49,225],"framework":[50],"integrating":[51],"target":[52,199],"prediction,":[53],"transcriptomic":[54],"analysis,":[55],"weighted":[56],"gene":[57],"co-expression":[58],"network":[59],"analysis":[60,151,166],"(WGCNA),":[61],"and":[62,76,84,154,176,219],"machine":[63],"learning":[64,88,134],"approaches.":[65],"Four":[66],"datasets":[68],"from":[69],"Gene":[70],"Expression":[71],"Omnibus":[72],"(GEO)":[73],"were":[74,79,94],"analyzed,":[75],"MNPN":[77,116,131,168],"predicted":[80],"using":[81,104],"ChEMBL,":[82],"PharmMapper,":[83],"SwissTargetPrediction":[85],"databases.":[86,120],"Machine":[87,133],"algorithms":[89],"(n":[90],"=":[91,148],"127":[92],"combinations)":[93],"evaluated":[95],"for":[96,209,213],"optimal":[97],"biomarker":[98],"identification,":[99],"model":[101],"interpretability":[102],"assessed":[103],"SHAP":[105,150],"(SHapley":[106],"Additive":[107],"exPlanations)":[108],"analysis.":[109],"Results:":[110],"Target":[111],"prediction":[112],"881":[114],"across":[118],"three":[119],"WGCNA":[121],"revealed":[122,167],"534":[123],"OSCC-associated":[124],"differentially":[125],"expressed":[126],"genes,":[127,139],"38":[129],"overlapping":[130],"targets.":[132],"optimization":[135],"13":[137],"hub":[138],"PLAU":[141,153,194],"demonstrating":[142],"the":[143,157,184,221],"highest":[144],"predictive":[145],"performance":[146],"(AUC":[147],"0.944).":[149],"confirmed":[152],"PLOD3":[155],"most":[158],"influential":[159],"contributors":[160],"to":[161],"disease":[162],"prediction.":[163],"Functional":[164],"enrichment":[165],"targets'":[169],"involvement":[170],"xenobiotic":[172],"response,":[173],"hypoxic":[174],"conditions,":[175],"aberrant":[177],"tissue":[178],"remodeling.":[179],"Conclusion:":[180],"This":[181],"study":[182],"provides":[183],"first":[185],"characterization":[188],"of":[189,223],"MNPN-associated":[190],"pathogenesis,":[192],"identifying":[193],"critical":[197],"therapeutic":[198],"exceptional":[201],"diagnostic":[202],"potential.":[203],"Our":[204],"findings":[205],"establish":[206],"foundation":[208],"developing":[210],"targeted":[211],"interventions":[212],"nitrosamine-associated":[216],"oral":[217],"cancers":[218],"demonstrate":[220],"power":[222],"integrative":[224],"approaches":[226],"environmental":[228],"carcinogen":[229],"research.":[230]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-05-21T06:26:12.895304","created_date":"2025-10-10T00:00:00"}