{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:07Z","timestamp":1790618227916,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and remains a major cause of cancer\u2010related mortality worldwide. Its poor clinical outcomes are largely attributed to late\u2010stage diagnosis and the limited accuracy of currently available diagnostic and prognostic biomarkers. Therefore, identifying novel molecular markers with improved sensitivity, specificity, and therapeutic relevance is essential for enhancing early detection and guiding personalized treatment strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To identify and prioritize novel candidate HCC biomarkers with diagnostic and prognostic value and potential therapeutic vulnerability using integrated multi\u2010omics, survival, functional dependency, and tumor microenvironment analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      We examined the mRNA and protein expression levels of 8 DEGs in HCC tissues in the TCGA and CPTAC datasets using UALCAN, which showed that MSTO1 and LIG1 were overexpressed consistently in HCC relative to normal liver tissues. Moreover, elevated expression levels of these genes were significantly associated with higher tumor grade and advanced stage. Kaplan\u2013Meier plotter survival data confirmed that increased expression of MSTO1 and LIG1 was associated with poorer overall survival. The DepMap CRISPR knockout data confirmed a functional dependency of both genes in HCC cell lines. CBioPortal analyses provided characterization of genomic alterations and enabled enrichment analysis of co\u2010expressed genes, and the TCGA\u2010UALCAN pan\u2010cancer analyses supported the assessment of tissue specificity across tumor types. TIMER3 analyses linked candidate gene expression with immune cell infiltration patterns. Diagnostic performance by ROC analysis showed excellent discrimination for MSTO1 (AUC\u2009=\u20090.987) and good discrimination for LIG1 (AUC\u2009=\u20090.897). Multivariate Cox regression with Benjamini\u2010Hochberg FDR correction across the eight genes supported MSTO1 as a candidate independent prognostic factor after adjustment for tumor stage, grade, etiology, age, and sex (HR\u2009=\u20091.29,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.035), whilst LIG1 showed no independent prognostic value. Promoter methylation of MSTO1 and ADH4, assessed via UALCAN, showed that both genes were significantly differentially methylated in the promoter region of primary HCC tissues compared with normal liver tissues. Our study also confirmed the biological and clinical relevance of established HCC biomarkers: TERT, IRAK1, and ADH4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MSTO1 and LIG1 emerged as candidate diagnostic biomarkers in HCC. Additionally, MSTO1 showed a candidate prognostic association with overall survival that remained significant after adjusting for tumor stage, grade, and etiology, as well as patients' age, but not after further adjustment for AFP status. Functional data also highlighted MSTO1 as a candidate therapeutic dependency. On the other hand, LIG1 showed no independent prognostic association in either multivariate model. Their differential expression and functional essentiality in HCC cell lines highlighted their value for further experimental and independent\u2010cohort validation before potential integration into biomarker development pipelines aimed at improving early detection and targeted therapy in HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70685","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T01:49:31Z","timestamp":1789350571000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive In Silico Analysis Identifies\n                    <scp>MSTO1<\/scp>\n                    and\n                    <scp>LIG1<\/scp>\n                    as Candidate Biomarkers With Diagnostic and Prognostic Relevance in Hepatocellular Carcinoma"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9484-8303","authenticated-orcid":false,"given":"Jana","family":"Hamad","sequence":"first","affiliation":[{"name":"Faculty of Sciences I, Laboratory of Cancer Biology &amp; Molecular Immunology Lebanese University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3465-4630","authenticated-orcid":false,"given":"Hussein","family":"Fayyad\u2010Kazan","sequence":"additional","affiliation":[{"name":"Faculty of Sciences I, Laboratory of Cancer Biology &amp; Molecular Immunology Lebanese University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3590-140X","authenticated-orcid":false,"given":"Fadi","family":"Abdel\u2010Sater","sequence":"additional","affiliation":[{"name":"Faculty of Sciences I, Laboratory of Cancer Biology &amp; Molecular Immunology Lebanese University  Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2024.102446"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512224"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S61146"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102893.2003.00487.x"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02779134"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741\u20108329(02)00212\u20104"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1934"},{"key":"e_1_2_12_10_1","volume-title":"Hepatocellular Carcinoma","author":"Asafo\u2010Agyei K. 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