{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:01:05Z","timestamp":1787032865279,"version":"build-2736575974"},"reference-count":30,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"GuangDong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2021A1515220180"],"award-info":[{"award-number":["2021A1515220180"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82273384"],"award-info":[{"award-number":["82273384"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82203748"],"award-info":[{"award-number":["82203748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lung adenocarcinoma (LUAD) is a highly malignant tumor with the highest mortality rate among all cancers. Early diagnosis and prognosis are important factors in treatment. Hepatic leukemia factor (HLF) is thought to be closely associated with lung cancer metastasis. It is downregulated in lung cancer tissues and negatively correlated with the number of metastasis-activating circulating tumor cells (CTCs) in the peripheral blood of patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method and Results<\/jats:title>\n                    <jats:p>\n                      In this study, we analyzed data from LUAD samples in TCGA and found that HLF was significantly upregulated in samples with EGFR mutations. Immunohistochemical (IHC) staining of 343 clinical samples also revealed a trend of HLF upregulation in patients with EGFR mutations. EGFR is one of the driver genes in non-small cell lung cancer (NSCLC), and the proportion in LUAD is as high as 50% in the East Asian population. In this study, EGFR mutation was not significantly correlated with the prognosis of LUAD patients and the number of CTC was also not related to EGFR mutation, but was closely related to HLF expression, with more CTCs being captured in the peripheral blood of patients with low expression of HLF (SI \u2264 4). By following up these 343 LUAD patients, high HLF expression (SI &gt; 4) was found to be an independent protective factor for progression-free survival regardless of EGFR status (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001), whereas high CTC count (&gt; 3) was an independent risk factor for recurrence or death in LUAD patients (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). When low HLF and high CTCs coexisted, patients had the shortest median survival time. Patients with low HLF or high CTCs appeared alone had a moderate median survival time. Patients had the longest median survival time when HLF was high and CTCs were low.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In summary, we believe that HLF expression in cancer tissues and the number of CTCs can be used as effective biomarkers for predicting the prognosis of LUAD, which plays an important role in clinical diagnosis and prognosis judgment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7717\/peerj.19092","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T04:26:28Z","timestamp":1742271988000},"page":"e19092","source":"Crossref","is-referenced-by-count":1,"title":["A combination of hepatic leukemia factor and circulating tumor cells serve as effective biomarkers for lung adenocarcinoma 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