2026-04-13T06:53:27Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/87882025-10-24T10:17:21Zcom_2072_378070com_2072_378040col_2072_378092

00925njm 22002777a 4500 dc Malik, Juliane author Klammer, Martin author Tanwandee, Tawesak author Esteban Feliu, Ignacio author Rolny, Vinzent author Piratvisuth, Teerha author Chan, Henry Lik Yuen author 2023-01-10T08:03:10Z 2023-01-10T08:03:10Z 2022-08-07 Carcinoma; Diagnosis; MicroRNAs Carcinoma; Diagnóstico; MicroARN Carcinoma; Diagnòstic; MicroARN Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Current guidelines for HCC management recommend surveillance of high-risk patients every 6 mo using ultrasonography. Serum biomarkers, like alpha-fetoprotein (AFP), protein induced by vitamin K absence/antagonist-II (PIVKA-II) and lectin-reactive AFP, show suboptimal performance for detection of HCC, which is crucial for successful resection or treatment. Thus, there is a significant need for new biomarkers to aid early diagnosis of HCC. Studies have shown that the expression level of human microRNAs (miRNAs), a small, non-coding RNA species released into the blood, can serve as an early marker for various diseases, including HCC. Aim: To evaluate the diagnostic role of miRNAs in HCC as single markers, signatures or in combination with known protein biomarkers. Methods: Our prospective, multicenter, case-control study recruited 660 participants (354 controls with chronic liver disease and 306 participants with HCC) and employed a strategy of initial screening by two independent methods, real-time quantitative PCR (n = 60) and next-generation sequencing (n = 100), to assess a large number of miRNAs. The results from the next-generation sequencing and real-time quantitative PCR screening approaches were then combined to select 26 miRNAs (including two putative novel miRNAs). Those miRNAs were analyzed for their diagnostic potential as single markers or in combination with other miRNAs or established protein biomarkers AFP and PIVKA-II via real-time quantitative PCR in training (n = 200) and validation cohorts (n = 300). Results: We identified 26 miRNAs that differentiated chronic liver disease controls from (early) HCC via two independent discovery approaches. Three miRNAs, miR-21-5p (miR-21), miR-320a and miR-186-5p, were selected by both methods. In the training cohort, only miR-21, miR-320d and miR-423 could significantly distinguish (Q < 0.05) between the HCC and chronic liver disease control groups. In the multivariate setting, miR-21 with PIVKA-II was selected as the best combination, resulting in an area under the curve of 0.87 for diagnosis and area under the curve of 0.74 for early diagnosis of HCC. In the validation cohort, only miR-21 and miR-423 could be confirmed as potential HCC biomarkers. A combination of miRNAs did not perform better than any single miRNA. Improvement of PIVKA-II performance through combination with miRNAs could not be confirmed in the validation panel. Two putative miRs, put-miR-6 and put-miR-99, were tested in the training and validation panels, but their expression could only be detected in very few samples and at a low level (cycle threshold between 31.24 and 34.97). Conclusion: miRNAs alone or as a signature in combination with protein biomarkers AFP and PIVKA-II do not improve the diagnostic performance of the protein biomarkers. http://hdl.handle.net/11351/8788 MicroARN Marcadors bioquímics Fetge - Càncer - Diagnòstic DISEASES::Neoplasms::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Liver Neoplasms::Carcinoma, Hepatocellular Other subheadings::Other subheadings::/diagnosis CHEMICALS AND DRUGS::Biological Factors::Biomarkers CHEMICALS AND DRUGS::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs ENFERMEDADES::neoplasias::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias hepáticas::carcinoma hepatocelular Otros calificadores::Otros calificadores::/diagnóstico COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores COMPUESTOS QUÍMICOS Y DROGAS::nucleótidos y nucleósidos de ácidos nucleicos::elementos antisentido (genética)::ARN antiparalelo::microARN Comprehensive evaluation of microRNA as a biomarker for the diagnosis of hepatocellular carcinoma