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Oncol."],"abstract":"<jats:p>Perihilar cholangiocarcinoma (PHCCA) has a poor prognosis, mainly due to diagnosis at an advanced stage. Cripto-1 functions as an oncogene and is highly expressed in several human cancers, however, its clinical application in PHCCA is poorly understood. Herein, we identified that Cripto-1 was released by PHCCA cells <jats:italic>via<\/jats:italic> exosomes <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Furthermore, an ELISA method was developed to detect exosomal Cripto-1 in the serum of 115 PHCCA patients, 47 cholangitis patients and 65 healthy controls, and it was found that exosomal Cripto-1 was increased in PHCCA patients and associated with metastasis. Compared with traditional serum tumor markers, CA19-9 and CEA, exosomal Cripto-1 demonstrated a larger area under ROC curve for PHCCA diagnosis. The cutoff value of exosomal Cripto-1 was 0.82, achieving a sensitivity of 79.1% and a specificity of 87.5%. As expected, exosomal Cripto-1 levels in immunohistochemically Cripto-1-high cases were significantly elevated compared to in Cripto-1-low cases. When measured 1-week postoperatively, Cripto-1 levels decreased on average from 1.25(0.96-3.26) to 0.85(0.62-1.82). Immunohistochemistry analysis showed Cripto-1 expression was negatively correlated with E-cadherin and was an independent prognostic biomarker for poor survival in PHCCA patients. In conclusion, exosomal Cripto-1 in sera can reflect its expression in the tissue of PHCAA patients and has the potential be a non-invasive biomarker for diagnosis and prognosis of PHCCA.<\/jats:p>","DOI":"10.3389\/fonc.2021.730615","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T05:01:35Z","timestamp":1628485295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Exosomal Cripto-1 Serves as a Potential Biomarker for Perihilar 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