{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T13:01:22Z","timestamp":1790427682309,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Objectives<\/jats:title>\n This study evaluated whether a protein\u2013protein interaction (PPI) network-based approach can link in vitro exposure-induced gene expression signatures to human disease modules.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Crocidolite, a well-established lung carcinogen, was used as a model of inhaled dust. Human immortalized type I alveolar epithelial cells were exposed to five doses of crocidolite, and RNA sequencing was performed. 253 asbestos exposure-responsive genes showing dose-dependent responses were defined as a crocidolite module. Lung cancer-related proteins were compiled from OMIM, GWAS Catalog, PheWAS, and ClinVar, yielding a lung cancer module of 90 proteins. The network proximity between the crocidolite module and the disease modules was evaluated using a z-score. Hub genes associated with both crocidolite exposure and lung cancer were identified by Cross-betweenness, Graph Kernel, and network propagation (NP). Method performance was assessed by receiver operating characteristic curve analysis using 11 guideline- and expert-selected lung cancer driver genes.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The crocidolite module showed significant proximity to the lung cancer module (Zc = \u22122.95), but not to the thyroid cancer module used as a negative control (Zc = 2.30). NP showed the highest performance for recovering driver genes (AUC = 0.974). NP-prioritized genes were enriched in PI3K\u2013Akt signaling, cancer-related pathways, EGFR\/ErbB signaling, apoptosis, and cellular senescence. The top hub genes included PARP1, STAT3, MYC, EGR1, CYP1A1, and SMAD3.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Integrating in vitro exposure transcriptomics with human disease modules through PPI-based network analysis may enable the computational evaluation of disease relevance and the identification of biologically meaningful hub genes for the assessment of occupational hazards.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/joccuh\/uiag060","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:50:29Z","timestamp":1790427029000},"source":"Crossref","is-referenced-by-count":0,"title":["Protein\u2013protein interaction network-based evaluation of lung cancer relevance and hub gene identification from in vitro crocidolite exposure signatures"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3583-3785","authenticated-orcid":false,"given":"Taisuke","family":"Tomonaga","sequence":"first","affiliation":[{"name":"Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Midori","family":"Iida","sequence":"additional","affiliation":[{"name":"Department of Bioscience and Bioinformatics, Faculty of Computer Science and Systems Engineering, Kyushu Institute of Technology , 680-4 Kawazu, Iizuka-shi, Fukuoka, 820-8502 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Takeshita","sequence":"additional","affiliation":[{"name":"Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan . 16-1 Onogawa, Tsukuba, Ibaraki, 305-8569 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidenori","family":"Higashi","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Engineering, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2955-4432","authenticated-orcid":false,"given":"Kazuhiro","family":"Yatera","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5339-6905","authenticated-orcid":false,"given":"Yasuo","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7694-6052","authenticated-orcid":false,"given":"Chinatsu","family":"Nishida","sequence":"additional","affiliation":[{"name":"Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Japan . 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu, Fukuoka, 807-8555 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,26]]},"container-title":["Journal of Occupational Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/joh\/advance-article-pdf\/doi\/10.1093\/joccuh\/uiag060\/71402565\/uiag060.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/joh\/advance-article-pdf\/doi\/10.1093\/joccuh\/uiag060\/71402565\/uiag060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:50:29Z","timestamp":1790427029000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/joh\/advance-article\/doi\/10.1093\/joccuh\/uiag060\/8836560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,26]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/joccuh\/uiag060","relation":{},"ISSN":["1348-9585"],"issn-type":[{"value":"1348-9585","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,26]]},"article-number":"uiag060"}}