Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors
IntroductionAdrenal tumors (ATs) encompass a wide differential diagnosis, necessitating a multi-step process for accurate identification. Liquid biopsy emerges as a promising non-invasive technique for distinguishing between malignant and benign, as well as hyperfunctioning and non-functioning cases...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Endocrinology |
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| author | Chrysoula Mytareli Vassiliki Kalotychou Alexandros Lafioniatis Gregory Kaltsas George N. Zografos Athina Markou Labrini Papanastasiou Athanasios Fountas Dimitra Argyro Vasilliadi Evanthia Kassi Evanthia Kassi Marina Mantzourani Anna Angelousi |
| author_facet | Chrysoula Mytareli Vassiliki Kalotychou Alexandros Lafioniatis Gregory Kaltsas George N. Zografos Athina Markou Labrini Papanastasiou Athanasios Fountas Dimitra Argyro Vasilliadi Evanthia Kassi Evanthia Kassi Marina Mantzourani Anna Angelousi |
| author_sort | Chrysoula Mytareli |
| collection | DOAJ |
| description | IntroductionAdrenal tumors (ATs) encompass a wide differential diagnosis, necessitating a multi-step process for accurate identification. Liquid biopsy emerges as a promising non-invasive technique for distinguishing between malignant and benign, as well as hyperfunctioning and non-functioning cases. Recent studies have highlighted the potential of microRNAs as circulating biomarkers; however, their clinical utility remains underexplored. This study aims to validate the diagnostic performance of selected circulating microRNAs, (miR-483-5p, miR-210, miR-335 and miR-22-3p), identified through microRNA profiling studies, as markers of malignancy or cortisol hypersecretion in a cohort of patients with ATs.MethodsWe collected serum samples from 75 patients with ATs, including 50 cases of adrenocortical adenomas (ACA) and 25 cases of adrenocortical carcinomas (ACC), along with 15 controls. In the ACC subgroup, 16 samples were obtained preoperatively or upon detection of recurrence (active ACC group), while the remaining from disease-free patients with long-term follow-up. Among the 56 patients with ATs evaluated preoperatively (50 with ACAs and 6 with ACC), 26 had non-functioning tumors, 22 exhibited mild autonomous cortisol secretion, and 8 had Cushing syndrome. Quantitative real-time polymerase chain reaction was employed to analyze microRNA expression.ResultsCirculating levels of miR-483-5p and miR-210 were significantly elevated in patients with active ACC compared to both ACAs (p<0.001 and p=0.004, respectively) and controls (p=0.02 and p = 0.03, respectively). Notably, miR-483-5p serum levels were higher in patients with active ACC compared to disease-free ACC patients (p = 0.01). MiR-483-5p demonstrated the best diagnostic accuracy for distinguishing active ACC cases from ACAs, achieving a sensitivity of 81.3% and a specificity of 88%, and from disease-free ACC patients, reaching sensitivity of 81.3% and specificity of 89%. MiR-22-3p serum levels successfully differentiated patients with Cushing syndrome from those with non-functioning ATs (area under the curve=AUC=0.800, 95% CI: 0.653–0.953, p=0.01) and controls (AUC= 0.800, 95% CI: 0.610–0.990, p=0.02). Additionally, circulating miR-22-3p levels exhibited a significant correlation with traditional diagnostic tests for hypercortisolism.ConclusionThis study supports the potential of a liquid biopsy approach as an innovative method for diagnosing and monitoring patients with ATs, offering a complementary tool to existing diagnostic methods. |
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| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj-art-50a761923e64490ab06f0bcda362df822025-01-30T05:10:10ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011610.3389/fendo.2025.15115201511520Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumorsChrysoula Mytareli0Vassiliki Kalotychou1Alexandros Lafioniatis2Gregory Kaltsas3George N. Zografos4Athina Markou5Labrini Papanastasiou6Athanasios Fountas7Dimitra Argyro Vasilliadi8Evanthia Kassi9Evanthia Kassi10Marina Mantzourani11Anna Angelousi12First Department of Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Propaedeutic and Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Surgery, ‘G. Gennimatas’ General Hospital of Athens, Athens, GreeceUnit of Endocrinology, and Diabetes Center, ‘G. Gennimatas’ General Hospital of Athens, Athens, GreeceUnit of Endocrinology, and Diabetes Center, ‘G. Gennimatas’ General Hospital of Athens, Athens, GreeceUnit of Endocrinology, and Diabetes Center, ‘G. Gennimatas’ General Hospital of Athens, Athens, GreeceDepartment of Endocrinology, Diabetes and Metabolism, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Evangelismos Hospital, Athens, GreeceDepartment of Propaedeutic and Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, National and Kapodistrian University of Athens, Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceFirst Department of Internal Medicine, European Reference Network on Rare Endocrine Conditions (ENDO-ERN), Laikon General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, GreeceIntroductionAdrenal tumors (ATs) encompass a wide differential diagnosis, necessitating a multi-step process for accurate identification. Liquid biopsy emerges as a promising non-invasive technique for distinguishing between malignant and benign, as well as hyperfunctioning and non-functioning cases. Recent studies have highlighted the potential of microRNAs as circulating biomarkers; however, their clinical utility remains underexplored. This study aims to validate the diagnostic performance of selected circulating microRNAs, (miR-483-5p, miR-210, miR-335 and miR-22-3p), identified through microRNA profiling studies, as markers of malignancy or cortisol hypersecretion in a cohort of patients with ATs.MethodsWe collected serum samples from 75 patients with ATs, including 50 cases of adrenocortical adenomas (ACA) and 25 cases of adrenocortical carcinomas (ACC), along with 15 controls. In the ACC subgroup, 16 samples were obtained preoperatively or upon detection of recurrence (active ACC group), while the remaining from disease-free patients with long-term follow-up. Among the 56 patients with ATs evaluated preoperatively (50 with ACAs and 6 with ACC), 26 had non-functioning tumors, 22 exhibited mild autonomous cortisol secretion, and 8 had Cushing syndrome. Quantitative real-time polymerase chain reaction was employed to analyze microRNA expression.ResultsCirculating levels of miR-483-5p and miR-210 were significantly elevated in patients with active ACC compared to both ACAs (p<0.001 and p=0.004, respectively) and controls (p=0.02 and p = 0.03, respectively). Notably, miR-483-5p serum levels were higher in patients with active ACC compared to disease-free ACC patients (p = 0.01). MiR-483-5p demonstrated the best diagnostic accuracy for distinguishing active ACC cases from ACAs, achieving a sensitivity of 81.3% and a specificity of 88%, and from disease-free ACC patients, reaching sensitivity of 81.3% and specificity of 89%. MiR-22-3p serum levels successfully differentiated patients with Cushing syndrome from those with non-functioning ATs (area under the curve=AUC=0.800, 95% CI: 0.653–0.953, p=0.01) and controls (AUC= 0.800, 95% CI: 0.610–0.990, p=0.02). Additionally, circulating miR-22-3p levels exhibited a significant correlation with traditional diagnostic tests for hypercortisolism.ConclusionThis study supports the potential of a liquid biopsy approach as an innovative method for diagnosing and monitoring patients with ATs, offering a complementary tool to existing diagnostic methods.https://www.frontiersin.org/articles/10.3389/fendo.2025.1511520/fulladrenocortical tumorsdiagnosisfollow-upmolecular biomarkerliquid biopsymicro-RNAs |
| spellingShingle | Chrysoula Mytareli Vassiliki Kalotychou Alexandros Lafioniatis Gregory Kaltsas George N. Zografos Athina Markou Labrini Papanastasiou Athanasios Fountas Dimitra Argyro Vasilliadi Evanthia Kassi Evanthia Kassi Marina Mantzourani Anna Angelousi Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors Frontiers in Endocrinology adrenocortical tumors diagnosis follow-up molecular biomarker liquid biopsy micro-RNAs |
| title | Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors |
| title_full | Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors |
| title_fullStr | Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors |
| title_full_unstemmed | Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors |
| title_short | Evaluation of microRNAs as liquid biopsy markers in adrenocortical tumors |
| title_sort | evaluation of micrornas as liquid biopsy markers in adrenocortical tumors |
| topic | adrenocortical tumors diagnosis follow-up molecular biomarker liquid biopsy micro-RNAs |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1511520/full |
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