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In this study, the goal was to identify circulating biomarkers based on a biomarker model for the early diagnosis and monitoring of patients with LCLM. An 8-gene panel identified in our previous study was validated in CTC, cfRNA and exosomes isolated from primary lung cancer with &amp; without metastasis. Further multivariate analysis including PCA &amp; ROC was performed to determine the sensitivity and specificity of the biomarker panel. Model validation cohort (<jats:italic>n<\/jats:italic>\u2009=\u200979) was used to verify the stability of the constructed predictive model. Further, clinic-pathological factors, survival analysis and immune infiltration correlations were also performed. In comparison to our previous tissue data, exosomes demonstrated a good discriminative value with an AUC of 0.7247, specificity (72.48%) and sensitivity (96.87%) for the 8-gene panel. Further individual gene patterns led us to a 5- gene panel that showed an AUC of 0.9488 (<jats:italic>p<\/jats:italic>\u2009=\u2009\u2009&lt;\u20090.001) and 0.9924 (<jats:italic>p<\/jats:italic>\u2009=\u2009\u2009&lt;\u20090.001) respectively for tissue and exosomes. Additionally, on validating the model in a larger cohort a risk score was obtained (RS\u2009&gt;\u20090.2) for prediction of liver metastasis with an accuracy of 95%. Survival analysis and immune filtration markers suggested that four exosomal markers were independently associated with poor overall survival. We report a novel blood-based exosomal biomarker panel for early diagnosis, monitoring of therapeutic response, and prognostic evaluation of patients with LCLM.<\/jats:p>","DOI":"10.1038\/s41598-024-63252-z","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T14:02:59Z","timestamp":1718373779000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel algorithm to differentiate between primary lung tumors and distant liver metastasis in lung cancers using an exosome based multi gene biomarker panel"],"prefix":"10.1038","volume":"14","author":[{"given":"Kanisha A.","family":"Shah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7985-1187","authenticated-orcid":false,"given":"Rakesh M.","family":"Rawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"issue":"2021","key":"63252_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3322\/caac.21654","volume":"71","author":"RL Siegel","year":"2021","unstructured":"Siegel, R. 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