{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T09:33:18Z","timestamp":1775727198637,"version":"3.50.1"},"reference-count":74,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"unspecified","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":"crossref","award":["82460133, 81960125"],"award-info":[{"award-number":["82460133, 81960125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Foundation Project of the Health Commission of Guizhou Province","award":["gzwkj2021-172"],"award-info":[{"award-number":["gzwkj2021-172"]}]},{"name":"Guizhou Provincial Basic Research Program","award":["[2020]1Y302"],"award-info":[{"award-number":["[2020]1Y302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatolithiasis (HL) is a prevalent condition in hepatobiliary surgery, often complicated by hepatatrophia. This study aimed to identify gene mutations in HL specimens with hepatatrophia and construct a mutation landscape using whole-exome sequencing (WES).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Genetic variants and copy number variations (CNVs) were compared between HL (\n                      <jats:italic>n<\/jats:italic>\n                      = 10) and normal control (NC,\n                      <jats:italic>n<\/jats:italic>\n                      = 10) specimens, encompassing 20 participants in total, using WES data. Hub genes within HL specimens were identified\n                      <jats:italic>via<\/jats:italic>\n                      the GeneCards database. The mutation frequencies and interaction patterns of these hub genes were explored, and their potential molecular mechanisms were assessed. A competing endogenous RNA (ceRNA) network and a transcription factor (TF)-mRNA network were established to clarify the regulatory mechanisms of hub genes. Therapeutic drugs targeting these hub genes were predicted using the DrugBank database, and molecular docking assessed the binding energies. Finally, hub gene expression was validated through reverse-transcription quantitative PCR (RT\u2013qPCR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven hub genes (\n                      <jats:italic>TMEM150B<\/jats:italic>\n                      ,\n                      <jats:italic>TNIP1<\/jats:italic>\n                      ,\n                      <jats:italic>ATRN<\/jats:italic>\n                      ,\n                      <jats:italic>FAAH<\/jats:italic>\n                      ,\n                      <jats:italic>FBXW4<\/jats:italic>\n                      ,\n                      <jats:italic>RAX<\/jats:italic>\n                      , and\n                      <jats:italic>WNT8B<\/jats:italic>\n                      ) were identified as uniquely mutated in HL specimens, with\n                      <jats:italic>TMEM150B<\/jats:italic>\n                      exhibiting the highest mutation frequency. The concurrent mutations of these genes are likely associated with the pathogenesis of HL combined with hepatatrophia. Functional enrichment analysis indicated that these hub genes are involved in the inflammatory response and Wnt signaling pathway. The ceRNA-TF network revealed that 296 lncRNAs (\n                      <jats:italic>e.g<\/jats:italic>\n                      ., C1RL-AS1) regulate six miRNAs (\n                      <jats:italic>e.g<\/jats:italic>\n                      ., hsa-miR-195-5p) targeting four hub genes, while 19 TFs (\n                      <jats:italic>e.g<\/jats:italic>\n                      ., NFYA, HINFP) also regulate these genes. Furthermore, fostamatinib exhibited the strongest binding affinity with\n                      <jats:italic>FAAH<\/jats:italic>\n                      , with a binding energy of \u22129.2 kcal\/mol, suggesting that it is a promising candidate for further investigation. RT\u2013qPCR confirmed that\n                      <jats:italic>TMEM150B<\/jats:italic>\n                      and\n                      <jats:italic>FAAH<\/jats:italic>\n                      expression levels were reduced in HL samples, while\n                      <jats:italic>TNIP1<\/jats:italic>\n                      ,\n                      <jats:italic>ATRN<\/jats:italic>\n                      ,\n                      <jats:italic>FBXW4<\/jats:italic>\n                      , and\n                      <jats:italic>WNT8B<\/jats:italic>\n                      were upregulated. Expression of\n                      <jats:italic>RAX<\/jats:italic>\n                      was not reliably detectable.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identified\n                      <jats:italic>TMEM150B<\/jats:italic>\n                      ,\n                      <jats:italic>TNIP1<\/jats:italic>\n                      ,\n                      <jats:italic>ATRN<\/jats:italic>\n                      ,\n                      <jats:italic>FAAH<\/jats:italic>\n                      ,\n                      <jats:italic>FBXW4<\/jats:italic>\n                      and\n                      <jats:italic>WNT8B<\/jats:italic>\n                      as key genes in the development of HL through inflammatory response and Wnt signaling pathways, providing new theoretical insights into therapeutic mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.21059","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T08:41:21Z","timestamp":1775724081000},"page":"e21059","source":"Crossref","is-referenced-by-count":0,"title":["Functional network analysis in hepatolithiasis: identifying novel therapeutic targets through whole-exome sequencing"],"prefix":"10.7717","volume":"14","author":[{"given":"Dan","family":"Tang","sequence":"first","affiliation":[{"name":"Suzhou Medical College of Soochow University, Suzhou, People\u2019s Republic of China, Suzhou, China"},{"name":"Department of General Surgery, Digestive Disease Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China"},{"name":"Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 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