Non-Coding RNAs in Adrenocortical Cancer: From Pathogenesis to Diagnosis

Non-coding RNA molecules including microRNAs and long non-coding RNAs (lncRNA) have been implicated in the pathogenesis of several tumors and numerous data support their applicability in diagnosis as well. Despite recent advances, the pathogenesis of adrenocortical cancer still remains elusive and there are no reliable blood-borne markers of adrenocortical malignancy, either. Several findings show the potential applicability of microRNAs as biomarkers of malignancy and prognosis, and there are some data on lncRNA as well. In this review, we present a synopsis on the potential relevance of non-coding RNA molecules in adrenocortical pathogenesis and their applicability in diagnosis from tissue and blood

A mikro-RNS-ek patogenetikai és diagnosztikai szerepe mellékvesekéreg-carcinomában

Adrenocortical tumours are quite prevalent. Most of these tumours are benign, hormonally inactive adrenocortical adenomas. Rare hormone-secreting adrenocortical adenomas are associated with severe clinical consequences, whereas the prognosis of the rare adrenocortical cancer is rather poor in its advanced stages. The pathogenesis of these tumours is only partly elucidated. MicroRNAs are small, non-coding RNA molecules that are pivotal in the regulation of several basic cell biological processes via the posttranscriptional regulation of gene expression. Their altered expression has been described in many tumours. Several tissue microRNAs, such as miR-483-5p, miR-503, miR-210, miR-335 and miR-195 were found to be differentially expressed among benign and malignant adrenocortical tumours, and these could also have pathogenic relevance. Due to their tissue specific and stable expression, microRNAs can be exploited in diagnostics as well. As the histological diagnosis of adrenocortical malignancy is difficult, microRNAs might be of help in the establishment of malignancy. Novel data show that microRNAs are secreted in various body fluids, projecting their applicability as biomarkers as part of liquid biopsy. In this review, we attempt to present a synopsis on the pathogenic relevance of microRNAs in adrenocortical tumours and their potential diagnostic applicability. Orv Hetil. 2018; 159(7): 245-251

Liquid biopsy for the assessment of adrenal cancer heterogeneity: where do we stand?

Almost 10 years have passed since the first attempts of liquid biopsy aimed at the characterisation of tumor cells present in the bloodstream from a regular sample of peripheral blood were performed. Liquid biopsy has been used to characterise tumor heterogeneity in various types of solid tumors including adrenocortical carcinoma. The development of molecular biology, genetics, and methodological advances such as digital PCR and next-generation sequencing allowed us to use besides circulating tumor cells a variety of circulating cell-free nucleic acids, DNAs, RNAs and microRNAs secreted by tumors into blood and other body fluids as specific molecular markers. These markers are used for diagnosis, to check tumor development, selecting efficient therapies, therapy monitoring and even possess prognostic power. In adrenocortical carcinoma, there are some studies reporting analysis of circulating tumor cells, circulating cell free DNA and microRNAs for assessing tumor heterogeneity. Among microRNAs, hsa-miR-483-5p seems to be the most important player. Combined with other microRNAs like hsa-miR-195, their expression correlates with recurrence-free survival. Most studies support the applicability of liquid biopsy for assessing temporal tumor heterogeneity (i.e. tumor progression) in adrenocortical cancer. In this mini-review, the available findings of liquid biopsy for assessing tumor heterogeneity in adrenocortical cancer are presented

Analysis of Circulating MicroRNAs In Vivo following Administration of Dexamethasone and Adrenocorticotropin

Purpose. The interaction of hormones of the pituitary-adrenal axis and adrenal cortex-associated circulating microRNAs is mostly unknown. We have studied the effects of dexamethasone and adrenocorticotropin on the expression of five circulating microRNAs (hsa-miR-27a, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, and hsa-miR-503) reported to be related to the adrenal cortex in plasma samples. Methods. Expression of microRNAs was studied in plasma samples of 10 individuals examined by 1 mg dexamethasone suppression test and another 10 individuals stimulated by 250 μg tetracosactide (adrenocorticotropin). Total RNA was isolated and microRNA expression was analyzed by real-time reverse transcription quantitative polymerase chain reaction normalized to cel-miR-39 as reference. Results. Only circulating hsa-miR-27a proved to be significantly modulated in vivo by hormonal treatments: its expression was upregulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Secreted hsa-miR-27a was significantly induced by dexamethasone in vitro in NCI-H295R cells, as well. The expression of hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration. Conclusions. hsa-miR-27a expression is modulated by hormones of the hypothalamic-pituitary-adrenal axis both in vitro and in vivo. The biological relevance of hsa-miR-27a modulation by hormones is unclear, but the responsiveness of circulating microRNAs to hormones of the pituitary-adrenal axis is noteworthy

Klímaváltozáshoz kapcsolódó természeti kockázatok helyi léptékű elemzése és a társadalmi felkészültség vizsgálata Közép- és Délkelet-Európában – Egy transznacionális projekt eredményei

ABSZTRAKT: Az elmúlt években felértékelődött a globális klímaváltozás regionális hatásainak kutatása, s ezzel párhuzamosan az időjárási szélsőségek okozta természeti veszélyhelyzetek társadalmi következményeinek minél pontosabb feltérképezése. Helyi szinten a természeti kockázatokkal összefüggésben a társadalom növekvő sérülékenysége jelent kihívásokat, így egyre nagyobb az igény a társadalom és a gazdaság részéről a felkészüléssel és megelőzéssel kapcsolatos információkra. Az Európai Unió támogatásával több olyan nemzetközi projekt valósult meg a Kárpát-medencében, amely különböző szempontok alapján vizsgálja a klímaváltozás okait és hatásait (pl. CARPATH CC, korábban ADAM, CECILIA, ENSEMBLES, PRUDENCE stb.). Ezek közül a SEERISK projekt kilenc közép- és délkelet-európai ország részvételével működik 2012 óta, és fő célkitűzése egységes kockázatértékelési módszertan kialakítása a klímaváltozás következtében felerősödő természeti veszélyhelyzetekre való megfelelő katasztrófavédelmi felkészülés céljából. A tanulmány elsődleges célja bemutatni azokat az eredményeket és tapasztalatokat, amelyek közös alapokra helyezhetik a klímaváltozással kapcsolatos kockázatok felmérését, térképi ábrázolását, az intézményi és lakossági felkészülést, a természeti veszélyhelyzetek kezelését. Az eredmények feldolgozása mellett részletesen ismertetjük a kockázatértékelési és a közösségi klímaadaptációs képesség elemzésére irányuló társadalomtudományi módszereket

Measurement of the Red Blood Cell Distribution Width Improves the Risk Prediction in Cardiac Resynchronization Therapy

Objectives. Increases in red blood cell distribution width (RDW) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) predict the mortality of chronic heart failure patients undergoing cardiac resynchronization therapy (CRT). It was hypothesized that RDW is independent of and possibly even superior to NT-proBNP from the aspect of long-term mortality prediction. Design. The blood counts and serum NT-proBNP levels of 134 patients undergoing CRT were measured. Multivariable Cox regression models were applied and reclassification analyses were performed. Results. After separate adjustment to the basic model of left bundle branch block, beta blocker therapy, and serum creatinine, both the RDW > 13.35% and NT-proBNP > 1975 pg/mL predicted the 5-year mortality (n = 57). In the final model including all variables, the RDW [HR = 2.49 (1.27-4.86); p = 0.008] remained a significant predictor, whereas the NT-proBNP [HR = 1.18 (0.93-3.51); p = 0.07] lost its predictive value. On addition of the RDW measurement, a 64% net reclassification improvement and a 3% integrated discrimination improvement were achieved over the NT-proBNP-adjusted basic model. Conclusions. Increased RDW levels accurately predict the long-term mortality of CRT patients independently of NT-proBNP. Reclassification analysis revealed that the RDW improves the risk stratification and could enhance the optimal patient selection for CRT