2026-09-16T03:04:55Zhttps://gredos.usal.es/oai/request

oai:gredos.usal.es:10366/1548092026-06-20T19:10:55Zcom_10366_3992com_10366_3947com_10366_3946com_10366_3823com_10366_3974col_10366_3993col_10366_3975

Serum metabolites as diagnostic biomarkers for cholangiocarcinoma, hepatocellular carcinoma, and primary sclerosing cholangitis Banales, Jesus M. Iñarrairaegui, Mercedes Arbelaiz, Ander Milkiewicz, Piotr Muntané, Jordi Muñoz-Bellvis, Luis La Casta, Adelaida González, Luis M. Arretxe, Enara Alonso, Cristina Martinez-Arranz, Ibon Lapitz, Ainhoa Santos-Laso, Alvaro Avila, Matias A. Martínez-Chantar, María L. Bujanda, Luis García Marín, José Juan Sangro, Bruno Rodríguez Macías, Rocío Isabel Serum Metabolites Diagnostic Biomarkers Cholangiocarcinoma Hepatocellular Carcinoma Primary sclerosing cholangitis [EN]Early and differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) by noninvasive methods represents a current clinical challenge. The analysis of low-molecular-weight metabolites by new high-throughput techniques is a strategy for identifying biomarkers. Here, we have investigated whether serum metabolome can provide useful biomarkers in the diagnosis of iCCA and HCC and could discriminate iCCA from HCC. Because primary sclerosing cholangitis (PSC) is a risk factor for CCA, serum metabolic profiles of PSC and CCA have also been compared. The analysis of the levels of lipids and amino acids in the serum of patients with iCCA, HCC, and PSC and healthy individuals (n = 20/group) showed differential profiles. Several metabolites presented high diagnostic value for iCCA versus control, HCC versus control, and PSC versus control, with areas under the receiver operating characteristic curve (AUC) greater than those found in serum for the nonspecific tumor markers carbohydrate antigen 19-9 (CA 19-9) and alpha-fetoprotein (AFP), commonly used to help in the diagnosis of iCCA and HCC, respectively. The development of an algorithm combining glycine, aspartic acid, SM(42:3), and SM(43:2) permitted to accurately differentiate in the diagnosis of both types of tumors (biopsy-proven). The proposed model yielded 0.890 AUC, 75% sensitivity, and 90% specificity. Another algorithm by combination of PC(34:3) and histidine accurately permitted to differentiate PSC from iCCA, with an AUC of 0.990, 100% sensitivity, and 70% specificity. These results were validated in independent cohorts of 14-15 patients per group and compared with profiles found in patients with nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Conclusion: Specific changes in serum concentrations of certain metabolites are useful to differentiate iCCA from HCC or PSC, and could help in the early diagnosis of these diseases. 2024-01-27T16:16:04Z 2024-01-27T16:16:04Z 2024-01-27T16:16:04Z 2019 info:eu-repo/semantics/article Banales, J. M., Iñarrairaegui, M., Arbelaiz, A., Milkiewicz, P., Muntané, J., Muñoz-Bellvis, L., La Casta, A., Gonzalez, L. M., Arretxe, E., Alonso, C., Martínez-Arranz, I., Lapitz, A., Santos-Laso, A., Avila, M. A., Martínez-Chantar, M. L., Bujanda, L., Marin, J. J. G., Sangro, B., & Macias, R. I. R. (2019). Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis. Hepatology, 70(2), 547-562. https://doi.org/10.1002/HEP.30319 0270-9139 http://hdl.handle.net/10366/154809 10.1002/hep.30319 1527-3350 eng https://doi.org/10.1002/HEP.30319 “Fondo de Investigaciones Sanitarias” (Carlos III Health Institute: PI15/01132 and PI18/01075 to J.M.B., PI16/00598 to J.J.G.M., PI16/01845 to B.S., PI16/01126 to M.A.A., PI16/00090 to J.M.), Spanish Ministry of Economy, Industry and Competitiveness (SAF2016‐75197‐R to R.I.R.M., SAF2017‐87301‐R to M.L.M.‐C.), Miguel Servet Programme (CON14/00129 to J.M.B.), “Diputación Foral de Gipuzkoa” (DFG15/010, DFG16/004 to J.M.B.), “Basque Foundation for Innovation and Health Research: EiTB Maratoia” (BIO15/CA/016/BD to J.M.B., BIO15/CA/016/BD to M.L.M.‐C.), Basque Country Department of Health (2013111173 to L.B., 2017111010 to J.M.B., 2013111114 to M.L.M.‐C.), the Andalusian Government (“Consejería de Economía, Innovación, Ciencia y Empleo”: CTS‐6264 and “Consejería de Salud”: PI‐0198‐2016 to J.M.), Junta de Castilla y León, Spain (SA063P17 to J.J.G.M.), European Comission Horizon 2020 project (SEP‐210503876; ESCALON to J.M.B.), and Proyecto Hepacare, Fundación La Caixa (to M.A.A.). http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Attribution-NonCommercial-NoDerivatives 4.0 Internacional Lippincott, Williams & Wilkins