{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T14:01:48Z","timestamp":1789999308670,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273325"],"award-info":[{"award-number":["82273325"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82273325"],"award-info":[{"award-number":["82273325"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Single-gene markers may help translate complex malignant epithelial states into bulk and tissue studies, but they must be distinguished from copy-number surrogates and prognostic biomarkers. We evaluated STEAP2 as a candidate marker of a lung adenocarcinoma (LUAD) malignant epithelial state. Methods: We integrated TCGA-LUAD bulk expression, subtype, copy-number and survival data with GSE131907 author-annotated malignant cells and GSE148071 CNV-high epithelial-like cells. Analyses included sample-level paired comparisons, sequencing-depth-adjusted mixed-effects models, cutoff and continuous-expression sensitivity analyses, and a pre-specified 7q gene benchmark. Results: STEAP2-high TCGA tumors were enriched for the Squamoid expression subtype (59.6% versus 23.3%; odds ratio, 4.69; 95% confidence interval [CI], 2.06\u201310.69). Iron-handling was the most reproducible single-cell feature: paired STEAP2-positive minus STEAP2-negative differences were 0.779 (95% CI, 0.605\u20130.952) in GSE131907 and 0.340 (95% CI, 0.304\u20130.377) in GSE148071, with consistent direction after removing STEAP2 from the score. Metabolic, interferon\/major histocompatibility complex and EMT\/YAP-like programs were context-dependent. STEAP2 ranked in the top decile of 106 evaluable 7q-window genes (rank fraction, 0.099) and retained state-composite association after adjustment for a 7q copy-number proxy and canonical Squamoid markers. The survival association attenuated after stage adjustment (hazard ratio, 1.17; p = 0.359). Conclusions: STEAP2 is a candidate marker of a 7q\/copy-number-associated iron-handling malignant epithelial state. The evidence supports state identification rather than prognosis, therapeutic targeting or causal driver claims.<\/jats:p>","DOI":"10.3390\/cancers18183050","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["STEAP2 Is a Candidate Marker of a 7q\/CNA-Associated Iron-Handling Malignant Epithelial State in Lung Adenocarcinoma"],"prefix":"10.3390","volume":"18","author":[{"given":"Xiang","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Cardiothoracic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Lei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4447-1053","authenticated-orcid":false,"given":"Yi","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature25183","article-title":"The biology and management of non-small cell lung cancer","volume":"553","author":"Herbst","year":"2018","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"The Cancer Genome Atlas Research Network (2014). 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