OBJECTIVES: The overexpression of plasminogen activator inhibitor-1 (PAI-1) was frequently observed during coronavirus disease 2019 (COVID-19), and it was found to be closely associated with disease severity. We have analyzed the PAI-1 status in fully recovered post-COVID patients. SUBJECTS AND METHODS: In a case-control and cross-sectional study, we compared 377 patients, 30-210 days after PCR-verified COVID-19 and 884 COVID-naive controls. RESULTS: Post-COVID patients ("cases") showed significantly higher plasma PAI-1 concentrations than COVID-naive controls. This difference remained significant even after complex adjustment by multiple regression. On the other hand, since the strongest covariate of increased PAI-1 was antihypertensive treatment, the difference between cases and controls in those who were on antihypertensives completely disappeared. In the subgroup of post-COVID patients only, we also found that highly symptomatic patients or those who required hospitalization in the acute phase showed significantly higher PAI-1 than patients with only mild symptoms of the disease. Similarly, the presence of β mutation increased the relative risk (≈11 times) of high post-COVID concentrations of PAI-1. Similarly, the presence of β mutation increased the relative risk (≈11 times) of high post-COVID concentrations of PAI-1. CONCLUSIONS: Increased values of PAI-1 can persist for several months after complete recovery from COVID-19 (namely, by β variant of the virus), and their expression also corresponded to clinical course of the disease.

• Klíčová slova
• Clinical course, PAI-1, Post-recovery status, SARS-CoV-2, Symptomatology,
• Publikační typ
• časopisecké články MeSH

BACKGROUND/AIM: New generation androgen receptor-targeting agents (ARTA) have been in the spotlight for their efficacy in metastatic castration-resistant prostate cancer (mCRPC). Prostate-specific antigen (PSA) represents one of the most commonly used serum cancer biomarkers worldwide. The present retrospective study focused on the prognostic role of serum PSA isoforms and their early dynamics in mCRPC patients treated with abiraterone acetate (ABI) or enzalutamide (ENZ). PATIENTS AND METHODS: The association between outcomes of 334 mCRPC patients treated with ABI or ENZ and the levels of serum total PSA (tPSA), free PSA (fPSA), [-2]proPSA and the Prostate Health Index (PHI) at baseline and one month after treatment initiation was analyzed retrospectively. RESULTS: In the multivariable Cox proportional hazards models, baseline tPSA>50 μg/l (p<0.001), and [-2]proPSA>300 ng/l (p=0.017) remained independent significant factors associated with inferior OS, while baseline fPSA>1.75 μg/l (p=0.050) and Δ [-2]proPSA >-50% approached statistical significance (p=0.062). The results of ROC analyses assessing the ability of baseline tPSA, fPSA, and [-2]proPSA to predict mortality within two years showed area under the curve (AUC) values of 0.709, 0.685, and 0.740, respectively. Among the subgroup with baseline tPSA≤20.0 μg/l, the results of ROC analyses for baseline tPSA, fPSA and [-2]proPSA showed AUC values of 0.441, 0.682, and 0.688, respectively. CONCLUSION: Our results suggest a significant correlation between pretreatment serum levels of tPSA and [-2]proPSA with OS in mCRPC patients receiving ARTA.

• Klíčová slova
• (−2)proPSA, ARTA, Castration-resistant prostate cancer, PSA, abiraterone acetate, enzalutamide, free PSA,
• MeSH
• abirateron terapeutické užití   aplikace a dávkování   MeSH
• androgenní receptory * metabolismus   MeSH
• benzamidy MeSH
• fenylthiohydantoin analogy a deriváty   aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádorové biomarkery krev   MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   patologie   krev   mortalita   diagnóza   MeSH
• nitrily MeSH
• prognóza MeSH
• prostatický specifický antigen * krev   MeSH
• protein - isoformy krev   MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abirateron MeSH
• androgenní receptory * MeSH
• benzamidy MeSH
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin MeSH
• nádorové biomarkery MeSH
• nitrily MeSH
• prostatický specifický antigen * MeSH
• protein - isoformy MeSH

BACKGROUND: Melanoma is the most aggressive skin cancer with ability to recur also after early-stage tumor surgery. The aim was to identify early-stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. METHODS: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre-amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. RESULTS: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild-type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). CONCLUSION: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. SIGNIFICANCE: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early-stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre- and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage.

• Klíčová slova
• BRAF V600E, S100B, ctDNA, ddPCR, melanoma,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * genetika   krev   MeSH
• melanom * genetika   krev   patologie   diagnóza   chirurgie   MeSH
• mutace * MeSH
• nádorové biomarkery * krev   genetika   MeSH
• nádory kůže * krev   genetika   patologie   diagnóza   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf * genetika   krev   MeSH
• S-100 kalcium vázající protein G, podjednotka beta * krev   genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• tekutá biopsie metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• nádorové biomarkery * MeSH
• protoonkogenní proteiny B-Raf * MeSH
• S-100 kalcium vázající protein G, podjednotka beta * MeSH
• S100B protein, human MeSH Prohlížeč

BACKGROUND/AIM: The management of patients with clear cell renal cell carcinoma (ccRCC) includes prognosis assessment based on TNM classification and biochemical markers. This approach stratifies patients with advanced ccRCC into groups of favorable, intermediate, and poor prognosis. The aim of the study was to improve prognosis estimation using microRNAs involved in the pathogenesis of ccRCC. PATIENTS AND METHODS: The study was based on a histologically-verified set of matched ccRCC FFPE tissue samples (normal renal tissue, primary tumor, metastasis, n=20+20+20). The expression of 2,549 microRNAs was analyzed using the SurePrint G3 Human miRNA microarray kit (Agilent Technologies). Prognostic value of significantly deregulated microRNAs was further evaluated on microRNA expression and clinical data of 475 patients obtained from TCGA Kidney Clear Cell Carcinoma (KIRC) database. RESULTS: There were 13 up-regulated and 6 down-regulated microRNAs in tumor tissues compared to control tissues. Among them, survival analysis revealed those with prognostic significance. Patients with high expression of miR-21, miR-27a, miR-34a, miR-106b, miR-210, and miR-342 showed significantly unfavorable outcome. The opposite was observed for miR-30e, patients with low expression had significantly shorter survival. CONCLUSION: The inclusion of these microRNAs in a prognostic panel holds the potential to enhance stratification scoring systems, on which the treatment of ccRCC patients is based.

• Klíčová slova
• Clear cell renal cell carcinoma, biomarkers, microRNA, prognosis, treatment,
• MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• karcinom z renálních buněk * genetika   patologie   mortalita   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• nádorové biomarkery * genetika   MeSH
• nádory ledvin * genetika   patologie   mortalita   metabolismus   MeSH
• prognóza MeSH
• regulace genové exprese u nádorů * MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• stanovení celkové genové exprese * MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mikro RNA * MeSH
• nádorové biomarkery * MeSH

BACKGROUND: The current obstructive sleep apnea (OSA) diagnostic uses polysomnography or limited polygraphy and requires specialized personnel and technical equipment. Glycoprotein biomarkers and microRNAs are being explored as a possible new method for screening. We aimed to evaluate whether certain biomarkers and microRNA, previously identified as related to OSA, could be influenced by factors such as gender, age, and obesity level in patients with OSA. METHODS: In this retrospective analytical study, patients with moderate to severe OSA (n = 130) were compared with the control group. Serum levels of selected biomarkers and microRNA were taken from both groups. The group of OSA patients was then stratified by gender, obesity level, and age to see the possible influence of those variables on biomarker levels. RESULTS: Levels of all studied biomarkers - C-reactive protein (CRP), high-sensitivity troponin I (hsTnI), pentraxin-3 (PTX-3), and microRNA-499 were significantly higher in patients with OSA compared to the control group. In the OSA group only hsTnI showed a statistically significant relationship with gender. Levels of CRP and hsTnI showed a significant dependence on the level of obesity. Dependency on age was proven for hsTnI. CRP, PTX-3, and microRNA-499 did not have any statistically significant relationship with age. CONCLUSION: We found that serum levels of pentraxin-3 and microRNA-499 in patients with moderate to severe obstructive sleep apnoea are independent of gender, obesity, and age. CRP was affected by the level of obesity and hsTnI was influenced by all 3 variables. We consider these findings important for further research of OSA biomarkers.

• Klíčová slova
• Biomarkers, Diagnostic process, Obstructive sleep apnoea, microRNA,
• MeSH
• biologické markery * krev   MeSH
• C-reaktivní protein * analýza   metabolismus   MeSH
• dospělí MeSH
• glykoproteiny krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * krev   MeSH
• obezita * krev   genetika   MeSH
• obstrukční spánková apnoe * krev   genetika   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• sérový amyloidový protein metabolismus   analýza   genetika   MeSH
• sexuální faktory MeSH
• troponin I krev   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery * MeSH
• C-reaktivní protein * MeSH
• glykoproteiny MeSH
• mikro RNA * MeSH
• MIRN499 microRNA, human MeSH Prohlížeč
• PTX3 protein MeSH Prohlížeč
• sérový amyloidový protein MeSH
• troponin I MeSH

Mutations in cancer-related genes are now known to be accompanied by epigenetic events in carcinogenesis by modification of the regulatory pathways and expression of genes involved in the pathobiology. Such cancer-related mutations, miRNAs and gene expression may be promising molecular markers of the most common papillary thyroid carcinoma (PTC). However, there are limited data on their relationships. The aim of this study was to analyse the interactions between BRAF mutations, selected microRNAs (miR-21, miR-34a, miR-146b, and miR-9) and the expression of selected genes (LGALS3, NKX2-1, TACSTD2, TPO) involved in the pathogenesis of PTC. The study cohort included 60 primary papillary thyroid carcinomas (PTC) that were classified as classical (PTC/C; n=50) and invasive follicular variant (PTC/F; n=10), and 40 paired lymph node metastases (LNM). BRAF mutation status in primary and recurrent/persistent papillary thyroid carcinomas was determined. The mutation results were compared both between primary and metastatic cancer tissue, and between BRAF mutation status and selected genes and miRNA expression in primary PTC. Furthermore, miRNAs and gene expression were compared between primary PTCs and non-neoplastic tissue, and local lymph node metastatic tumor, respectively. All studied markers showed several significant mutual interactions and contexts. In conclusion, to the best our knowledge, this is the first integrated study of BRAF mutational status, the expression levels of mRNAs of selected genes and miRNAs in primary PTC, and paired LNM.

• Klíčová slova
• BRAF, MicroRNA, LGALS3, NKX2-1, Papillary thyroid carcinoma, TACSTD2, TPO,
• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy * genetika   patologie   MeSH
• mikro RNA * genetika   MeSH
• mutace * MeSH
• nádorové biomarkery genetika   MeSH
• nádory štítné žlázy * genetika   patologie   MeSH
• papilární karcinom štítné žlázy * genetika   patologie   MeSH
• protoonkogenní proteiny B-Raf * genetika   MeSH
• regulace genové exprese u nádorů MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BRAF protein, human MeSH Prohlížeč
• mikro RNA * MeSH
• nádorové biomarkery MeSH
• protoonkogenní proteiny B-Raf * MeSH

BACKGROUND/AIM: Targeted therapy has become increasingly important in treating lung adenocarcinoma, the most common subtype of lung cancer. Next-generation sequencing (NGS) enables precise identification of specific genetic alterations in individual tumor tissues, thereby guiding targeted therapy selection. This study aimed to analyze mutations present in adenocarcinoma tissues using NGS, assess the benefit of targeted therapy and evaluate the progress in availability of targeted therapies over last five years. PATIENTS AND METHODS: The study included 237 lung adenocarcinoma patients treated between 2018-2020. The Archer FusionPlex CTL panel was used for NGS analysis. RESULTS: Gene variants covered by the panel were detected in 57% patients and fusion genes in 5.9% patients. At the time of the study, 34 patients (14.3% of patients) were identified with a targetable variant. Twenty-five patients with EGFR variants, 8 patients with EML4-ALK fusion and one patient with CD74-ROS1 fusion received targeted therapy. Prognosis of patients at advanced stages with EGFR variants treated by tyrosine kinase inhibitors and patients with EML4-ALK fusion treated by alectinib was significantly favorable compared to patients without any targetable variant treated by chemotherapy (p=0.0172, p=0.0096, respectively). Based on treatment guidelines applicable in May 2023, the number of patients who could profit from targeted therapy would be 64 (27.0% of patients), this is an increase by 88% in comparison to recommendations valid in 2018-2020. CONCLUSION: As lung adenocarcinoma patients significantly benefit from targeted therapy, the assessment of mutational profiles using NGS could become a crucial approach in the routine management of oncological patients.

• Klíčová slova
• NGS, lung adenocarcinoma, prognosis, targeted therapy,
• MeSH
• adenokarcinom plic * farmakoterapie   genetika   MeSH
• erbB receptory genetika   MeSH
• lidé MeSH
• mutace MeSH
• nádory plic * farmakoterapie   genetika   patologie   MeSH
• protoonkogenní proteiny genetika   MeSH
• tyrosinkinasové receptory genetika   MeSH
• tyrosinkinasy genetika   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• erbB receptory MeSH
• protoonkogenní proteiny MeSH
• tyrosinkinasové receptory MeSH
• tyrosinkinasy MeSH

BACKGROUND/AIM: Enzalutamide (ENZ) and abiraterone acetate with prednisone (AAP) represent novel hormonal therapies used in the treatment of metastatic castration-resistant prostate cancer (mCRPC). The aim of the study was to assess the long-term outcome of mCRPC patients treated with ENZ or AAP in real-life clinical practice. PATIENTS AND METHODS: The outcomes of 337 mCRPC patients treated with ENZ or AAP were retrospectively analysed. RESULTS: Median radiographic progression-free (rPFS) and overall survival (OS) of patients treated in the first line (pre-chemotherapy) was 13.89 (95% CI=12.40-16.80) and 31.02 (95% CI=24.27-37.44) months vs. 10.97 (95% CI=8.97-14.82) and 26.57 (95% CI=15.97-33.92) months for those treated in the second line (post-chemotherapy). We found inferior survival for patients with synchronous metastases, high Gleason score (GS) and visceral metastases. CONCLUSION: The efficacy of both ENZ and AAP in mCRPC patients is herein confirmed. Synchronous metastases, high GS and visceral metastases were identified as significant adverse prognostic factors.

• Klíčová slova
• Enzalutamide, abiraterone acetate, castration-resistant prostate cancer, metastatic, real-life practice,
• MeSH
• abirateron * terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• nitrily MeSH
• prednison terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abirateron * MeSH
• enzalutamide MeSH Prohlížeč
• nitrily MeSH
• prednison MeSH

BACKGROUND/AIM: The treatment of advanced clear cell renal cell carcinoma (ccRCC) is based on stratification of patients according to prognosis (favorable, intermediate, and poor). The aim of the study was to improve prognostication by biomarkers involved in angiogenesis. PATIENTS AND METHODS: The study group consisted of 20 patients who underwent surgery for ccRCC. Gene expression analysis was peformed on a set of matched (primary tumor, metastasis, n=20+20) FFPE tissue samples. An additional analysis was done on expression data of 606 patients obtained from the TCGA Kidney Clear Cell Carcinoma (KIRC) database. Quantitative estimation of mRNA of selected genes (TaqMan human Angiogenesis Array, 97 genes) was performed by a real-time RT-PCR method with TaqMan® arrays. RESULTS: Using the Cox regression model, 4 genes (PDGFB, FGF4, EPHB2 and BAI1) were identified whose expression was related to progression-free interval (PFI). Further analysis using the Kaplan Meier method conclusively revealed the relationship of BAI1 expression to prognosis (both datasets). Patients with higher BAI1 expression had significantly shorter PFI and overall survival. CONCLUSION: We showed that tumor tissue BAI1 expression level is a prognostic marker in ccRCC. Therefore, this gene might be involved in a prognostic panel to improve scoring systems on which the management of metastatic ccRCC patients is based.

• Klíčová slova
• BAI1, Clear cell renal cell carcinoma, FFPE, biomarkers, prognosis, treatment,
• MeSH
• analýza přežití MeSH
• angiogenní proteiny genetika   MeSH
• karcinom z renálních buněk genetika   mortalita   chirurgie   MeSH
• lidé MeSH
• nádorové biomarkery genetika   MeSH
• nádory ledvin genetika   mortalita   chirurgie   MeSH
• prognóza MeSH
• receptory spřažené s G-proteiny genetika   MeSH
• regresní analýza MeSH
• regulace genové exprese u nádorů MeSH
• sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
• stanovení celkové genové exprese metody   MeSH
• upregulace * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ADGRB1 protein, human MeSH Prohlížeč
• angiogenní proteiny MeSH
• nádorové biomarkery MeSH
• receptory spřažené s G-proteiny MeSH

Background: Obstructive sleep apnea syndrome (OSAS) is one of the most common sleep-related breathing disorders. The aim of this study was to improve diagnostics in OSAS using blood circulating biomarkers. We consider the potential of cardiac-specific miRNAs in the diagnosis and risk assessment of cardiovascular complications. Materials & methods: Plasmatic levels of miR-1-3p, miR-133a-3p and miR-499a-5p were measured by reverse transcription-PCR and compared with the clinical status of OSAS patients and controls. Results: The level of miR-499 was higher (p = 0.0343) in OSAS patients (mean expression: 0.00561) compared with the controls (mean expression: 0.00003), using the multivariate logistic regression. Conclusion: The role of miR-499 in gene expression regulation during hypoxia and our findings indicate that miR-499 could be a new diagnostic biomarker for OSAS.

• Klíčová slova
• biomarker, cardiovascular disease, miR1, miR133a, miR499, miRNA, sleep apnea syndrome,
• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• mikro RNA genetika   MeSH
• multivariační analýza MeSH
• obstrukční spánková apnoe krev   diagnóza   genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• regulace genové exprese MeSH
• ROC křivka MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• mikro RNA MeSH
• MIRN499 microRNA, human MeSH Prohlížeč