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Besides tumor\u2010initiating and promoting DNA, RNA, and epigenetic alterations, aberrant cell metabolism is a hallmark of carcinogenesis. This study aimed to identify SqCC\u2010specific key regulators that could eventually be used as new anticancer targets. Transcriptional and metabolomic data were gathered for a cohort of resected lung cancers. SqCC\u2010specific differentially expressed genes were integrated with metabolic data. Findings were validated in cohorts of tumors, normal specimens, and cell lines.\n                    <jats:italic>In situ<\/jats:italic>\n                    protein expression of SLC6A8 was investigated. Differential gene expression analysis identified a subset of SqCC\u2010specific genes with metabolic functions through the Reactome database, and\/or correlated to specific metabolites through GEMs models. Metabolic profiling identified seven SqCC\u2010specific metabolites, of which increased creatine levels, in particular, matched to SqCC\u2010specific expression of\n                    <jats:italic>SLC6A8<\/jats:italic>\n                    . Expression of the gene appeared tumor cell\u2010associated. Elevated creatine levels and overexpression of its transporter SLC6A8 appear a distinct metabolic feature of SqCC. Considering ongoing clinical trials in other malignancies, exploring SLC6A8 inhibition in SqCC appears motivated based on a metabolic addiction hypothesis.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70121","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T06:01:48Z","timestamp":1756965708000},"page":"3806-3820","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multi\u2010omic profiling of squamous cell lung cancer identifies metabolites and related genes associated with squamous cell carcinoma"],"prefix":"10.1002","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5254-5115","authenticated-orcid":false,"given":"Johan","family":"Staaf","sequence":"first","affiliation":[{"name":"Division of Oncology, Department of Clinical Sciences Lund Lund University  Sweden"},{"name":"Division of Translational Cancer Research, Department of Laboratory Medicine Lund 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