{"doi":"10.1101/2025.02.03.636354","title":"Identifying Sex Differences in Lung Adenocarcinoma Using Multi-Omics Integrative Protein Signaling Networks","abstract":"Lung adenocarcinoma (LUAD) exhibits differences between the sexes in incidence, prognosis, and therapy, suggesting underexplored molecular mechanisms. We conducted an integrative multi-omics analysis using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) datasets to contrast transcriptomes and proteomes between sexes. We used TIGER to analyze TCGA-LUAD expression data and found sex-biased activity of transcription factors (TFs); we used PTM-SEA with CPTAC-LUAD proteomics data and found sex-biased kinase activity. We combined these to construct a kinase-TF signaling network and discovered druggable pathways linked to cancer-related processes. We also found significant sex biases in clinically relevant TFs and kinases, including NR3C1, AR, and AURKA. Using the PRISM drug screening database, we identified potential sex-specific drugs, such as glucocorticoid receptor agonists and aurora kinase inhibitors. Our findings emphasize the importance of considering sex and using multi-omics network methods to discover personalized cancer therapies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":556008,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8461,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1022980,"name":"Enakshi Saha","orcid":"0000-0003-2938-539X","position":1,"is_corresponding":false},{"id":1165225,"name":"Jonas Fischer","orcid":"0000-0003-4225-9734","position":2,"is_corresponding":false},{"id":6591,"name":"Marouen Ben Guebila","orcid":"0000-0001-5934-966X","position":3,"is_corresponding":false},{"id":983541,"name":"Viola Fanfani","orcid":"0000-0003-3852-6908","position":4,"is_corresponding":false},{"id":728147,"name":"Katherine H. Shutta","orcid":"0000-0003-0402-3771","position":5,"is_corresponding":false},{"id":736342,"name":"Megha Padi","orcid":"0000-0002-3446-4562","position":6,"is_corresponding":false},{"id":36157,"name":"Kimberly Glass","orcid":"0000-0003-4394-5779","position":7,"is_corresponding":false},{"id":24957,"name":"Dawn L. DeMeo","orcid":"0000-0001-9653-0636","position":8,"is_corresponding":false},{"id":226258,"name":"Camila M. Lopes‐Ramos","orcid":"0000-0003-0284-7371","position":9,"is_corresponding":false},{"id":6384,"name":"John Quackenbush","orcid":"0000-0002-2702-5879","position":10,"is_corresponding":false},{"id":1248731,"name":"Chen Chen","orcid":"0000-0002-8042-7201","position":0,"is_corresponding":true}],"reference_count":80,"raw_metadata":null,"created_at":"2026-07-19T02:55:03.976486Z","pmid":"39975108","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}