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 * krev metabolismus MeSH
- antagonisté androgenních receptorů terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- metastázy nádorů MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie krev patologie mortalita MeSH
- prognóza MeSH
- prostatický specifický antigen * krev MeSH
- protein - isoformy * krev MeSH
- retrospektivní studie 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
- antagonisté androgenních receptorů MeSH
- nádorové biomarkery MeSH
- prostatický specifický antigen * MeSH
- protein - isoformy * MeSH
BACKGROUND: To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa). METHODS: 122 PCa patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated. RESULTS: PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p < 0.001). CRPC overall survival was independently associated with LDAH and PSA (p = 0.0168, p < 0.001). CONCLUSION: The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.
- Klíčová slova
- DNA methylation, Epigenetics, PET/CT, PSMA, Prostate cancer, cfDNA,
- MeSH
- cirkulující nádorová DNA genetika krev MeSH
- EDTA analogy a deriváty MeSH
- izotopy gallia * MeSH
- lidé středního věku MeSH
- lidé MeSH
- metylace DNA * genetika MeSH
- nádorové biomarkery * genetika krev MeSH
- nádory prostaty rezistentní na kastraci genetika krev diagnostické zobrazování MeSH
- nádory prostaty * genetika krev diagnostické zobrazování MeSH
- PET/CT * metody MeSH
- prognóza MeSH
- prostatický specifický antigen * krev genetika MeSH
- průřezové studie MeSH
- radioizotopy galia * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- Názvy látek
- cirkulující nádorová DNA MeSH
- EDTA MeSH
- gallium 68 PSMA-11 MeSH Prohlížeč
- izotopy gallia * MeSH
- nádorové biomarkery * MeSH
- prostatický specifický antigen * MeSH
- PSMA-11 MeSH Prohlížeč
- radioizotopy galia * MeSH
Gliomas are the most common and lethal forms of malignant brain tumors. We attempted to identify the role of the aging-suppressor Klotho gene and Klotho protein in the immunopathogenesis of gliomas. We examined Klotho genetic variants by PCR-RFLP and measured serum Klotho levels using the ELISA method. We found a statistically significantly increased frequency of rs1207568A allele and rs1207568 GA genotypes in co-dominant, dominant and over-dominant models in grade IV as compared to grade II and III glioma patients. The levels of soluble α Klotho (sαKL) were significantly lower in grade III and IV glioma patients than in healthy controls (p = 0.034; 0.0083). Patients with sαKL levels above 2500 pg/mL survived significantly longer than patients with sαKL below 2500 pg/mL (p = 0.038). We also found a positive correlation of the serum levels of sαKL with seven biomarkers, like angiogenic vascular endothelial growth factor (p = 0.0008), chemokine fractalkine (p = 0.0009), interferon γ (p = 0.003), glial derived neurotrophic factor (p = 0.0268), pro-inflammatory and pro-Th1 cytokine IL-6 (p = 0.0347), anti-inflammatory, pro-Th2 cytokines IL-4 (p = 0.0037) and IL-13 (p = 0.0004). Our results suggest the impact of Klotho genetic variants and Klotho levels on advanced-grade glioma.
- Klíčová slova
- Klotho gene, cytokines, glioma, inflammation, overall survival, α klotho,
- MeSH
- cytokiny * krev genetika MeSH
- dospělí MeSH
- genotyp MeSH
- gliom * genetika krev mortalita patologie MeSH
- glukuronidasa * krev genetika MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev genetika MeSH
- nádory mozku * genetika krev mortalita patologie MeSH
- proteiny Klotho * MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- stupeň nádoru * 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
- cytokiny * MeSH
- glukuronidasa * MeSH
- nádorové biomarkery MeSH
- proteiny Klotho * MeSH
BACKGROUND: Diffuse midline glioma, H3 K27-altered (DMG) is a fatal tumour that arises in the midline structures of the brain. When located in the pons, it is more commonly referred to as diffuse intrinsic pontine glioma (DIPG). DMG/DIPG is usually diagnosed when children are < 10 years, and it has a median overall survival of < 12 months after diagnosis. Radiological imaging is still the gold standard for DIPG diagnosis while the use of biopsy procedures led to our knowledge on its biology, such as with the identification of the canonical histone H3K27M mutation. However, the need to improve survival encourages the development of non-invasive, fast and inexpensive assays on biofluids for optimizing molecular diagnoses in DMG/DIPG. Here, we propose a rapid, new, imaging and epigenetics-based approach to diagnose DMG/DIPG in the plasma of paediatric patients. METHODS: A total of 20 healthy children (mean age: 10.5 years) and 24 children diagnosed with DMG/DIPG (mean age: 8.5 years) were recruited. Individual histones (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2), histone dimers and nucleosomes were assayed in biofluids by means of a new advanced flow cytometry ImageStream(X)-adapted method. RESULTS: We report a significant increase in circulating histone dimers and tetramers (macroH2A1.1/H2B versus control: p value < 0.0001; macroH2A1.2/H2B versus control: p value < 0.0001; H2A/H2B versus control: p value < 0.0001; H3/H4 versus control: p value = 0.008; H2A/H2B/H3/H4 versus control: p value < 0.0001) and a significant downregulation of individual histones (H2B versus control: p value < 0.0001; H3 versus control: p value < 0.0001; H4 versus control: p value < 0.0001). Moreover, histones were also detectable in the cerebrospinal fluid (CSF) of patients with DMG/DIPG and in the supernatant of SF8628, OPBG-DIPG002 and OPBG-DIPG004 DMG/DIPG cell lines, with patterns mostly similar to each other, but distinct compared to blood plasma. CONCLUSIONS: In summary, we identified circulating histone signatures able to detect the presence of DMG/DIPG in biofluids of children, using a rapid and non-invasive ImageStream(X)-based imaging technology, which may improve diagnosis and benefit the patients.
- MeSH
- difuzní intrinsický pontinní gliom genetika diagnóza krev MeSH
- dítě MeSH
- epigeneze genetická MeSH
- gliom genetika diagnóza krev patologie diagnostické zobrazování MeSH
- histony * genetika metabolismus krev MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- nádorové biomarkery krev MeSH
- nádory mozkového kmene genetika diagnóza krev diagnostické zobrazování patologie metabolismus MeSH
- předškolní dítě MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- histony * MeSH
- nádorové biomarkery MeSH
PURPOSE: TACE induces variable systemic effects by producing factors that promote inflammation, oncogenesis, and angiogenesis. Here we compare concentrations of microRNAs (miR-21, miR-210 and miR-34a) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) patients undergoing TACE with degradable (DSM) and nondegradable (DEB) particles and potential use of these biomarker changes for prediction of patient outcomes. MATERIALS AND METHODS: Overall, 52 patients with HCC treated with DSM TACE (24 patients) and DEB TACE (28 patients) were included in this prospective study. Concentrations of studied biomarkers were measured from blood plasma preprocedurally, immediately (< 90 min) postprocedurally, and 24-h after TACE. Levels were compared between DSM and DEB TACE and correlated with treatment response six and 12 months after the first TACE. RESULTS: Both DSM and DEB TACE elevated plasma levels of miR-21, miR-34a, and miR-210 at 24 h post-procedure compared to baseline levels (FC 1.25-4.0). MiR-34a elevation immediately after TACE was significantly associated with nonprogressive disease compared to those with progressive disease at both six months (FCa: p = 0.014) and 12 months (FCa: p = 0.029) post-TACE. No significant biomarker changes were found between the embolization particle groups. However, VEGF levels showed a decrease only in the DSM TACE group (FC24: p = < 0.001). CONCLUSION: Embolization particle type did not significantly impact miRNA or VEGF changes post-TACE. However, miR-34a elevation immediately after the procedure predicts better patient outcome and may prove useful as a biomarkers for the monitoring of clinical outcomes. LEVEL OF EVIDENCE: Level 3 Prospective cohort study.
- Klíčová slova
- Degradable and nondegradable particles, Hepatocellular carcinoma, Hypoxia, MicroRNA and vascular endothelial growth factor, Transarterial chemoembolization, Tumor suppressor,
- MeSH
- biologické markery krev MeSH
- chemoembolizace * metody MeSH
- hepatocelulární karcinom * terapie krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikro RNA * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * terapie genetika krev MeSH
- prospektivní studie MeSH
- senioři MeSH
- vaskulární endoteliální růstový faktor A * krev MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- mikro RNA * MeSH
- MIRN21 microRNA, human MeSH Prohlížeč
- MIRN34 microRNA, human MeSH Prohlížeč
- nádorové biomarkery * MeSH
- vaskulární endoteliální růstový faktor A * MeSH
We aimed to detect the levels of T-lympho-cyte subsets and serum tumour markers in patients with non-small cell lung cancer (NSCLC) before chemotherapy, and to investigate the predictive value of their combined detection for the prognosis of NSCLC patients undergoing chemotherapy. The clinical data of 110 NSCLC patients treated with chemotherapy from January 2019 to February 2021 were analysed retrospectively. All patients were followed up for one year and divided into good prognosis group (surviving cases) and poor prognosis group (deceased cases). The predictive value of T-lymphocyte subsets combined with serum tumour markers for prognosis was analysed. The proportions of patients with tumour-node-metastasis stages III-IV, lymph node metastasis and poor differentiation were higher in the poor prognosis group than those in the good prognosis group (P < 0.05). Cox regression analysis revealed that high expression of CD4+ and CEA represented protective factors for poor prognosis of NSCLC patients undergoing chemotherapy [odds ratio (OR) < 1, P < 0.05], while high expression of CA125 was a risk factor (OR > 1, P < 0.05). All the areas under the receiver operating characteristic curves of single indicator detection (CD4+, CEA and CA125 levels) and their combined detection for prediction of the poor prognosis of NSCLC patients undergoing chemotherapy were > 0.70, which was highest in the case of combined detection. T-lymphocyte subsets and serum tumour markers are closely related to the prognosis of NSCLC patients undergoing chemotherapy, and their combined detection is of high predictive value.
- Klíčová slova
- T-lymphocyte subset, non-small cell lung cancer, prediction, prognosis, tumour marker,
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * krev MeSH
- nádory plic * farmakoterapie krev patologie MeSH
- nemalobuněčný karcinom plic * farmakoterapie krev MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- senioři MeSH
- T-lymfocyty - podskupiny * 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
- nádorové biomarkery * MeSH
INTRODUCTION: We evaluate the predictive and prognostic value of insulin-like growth factor-I (IGF-1), IGF binding protein-2 (IGFBP-2) and -3 (IGFBP-3) in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS: This is a retrospective analysis of a multi-institutional database comprising 753 patients who underwent RNU for UTUC and had a preoperative plasma available. Logistic and Cox regression analyses were performed. The discriminative ability and clinical utility of the models was calculated using the lasso regression test, area under receiver operating characteristics curves, C-index, and decision curve analysis (DCA). RESULTS: Lower preoperative plasma levels of IGFBP-2 and -3 independently correlated with increased risks of lymph node metastasis, pT3/4 disease, nonorgan confined disease, and worse recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) (all P ≤ .004). The addition of both IGFBP-2 and -3 to a postoperative multivariable model, that included standard clinicopathologic characteristics, improved the model's concordance index by 10%, 9%, and 8% for RFS, CSS, and OS, respectively. On DCA, addition of both IGFBP-2 and -3 to base models improved their performance for RFS, CSS, and OS by a statistically and clinically significant margin. Plasma IGF-1 was not associated with any of outcomes. CONCLUSIONS: We confirmed that a lower plasma levels of IGFBP-2 and -3 both are independent and clinically significant predictors of adverse pathological features and survival outcomes in UTUC patients treated with RNU. These findings might help guide the clinical decision-making regarding perioperative systemic therapy and follow-up scheduling.
- Klíčová slova
- IGF-1, IGFBP-2, IGFBP-3, Upper tract, Urothelial carcinoma,
- MeSH
- hodnocení rizik metody MeSH
- IGFBP-3 krev MeSH
- insulinu podobný růstový faktor I * metabolismus MeSH
- karcinom z přechodných buněk chirurgie krev patologie mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nefroureterektomie * metody MeSH
- peptidy podobné insulinu MeSH
- předoperační období MeSH
- prognóza MeSH
- protein 2 vázající insulinu podobné růstové faktory * krev MeSH
- retrospektivní studie MeSH
- senioři MeSH
- urologické nádory chirurgie krev patologie mortalita MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- IGF1 protein, human MeSH Prohlížeč
- IGFBP-3 MeSH
- IGFBP2 protein, human MeSH Prohlížeč
- IGFBP3 protein, human MeSH Prohlížeč
- insulinu podobný růstový faktor I * MeSH
- nádorové biomarkery MeSH
- peptidy podobné insulinu MeSH
- protein 2 vázající insulinu podobné růstové faktory * MeSH
BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- lokální recidiva nádoru * patologie chirurgie krev MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty * chirurgie patologie krev mortalita MeSH
- následné studie MeSH
- prognóza MeSH
- prostatektomie * metody MeSH
- prostatický specifický antigen * krev MeSH
- retrospektivní studie MeSH
- senioři MeSH
- záchranná terapie * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- nádorové biomarkery MeSH
- prostatický specifický antigen * MeSH
BACKGROUND: Malignant liver tumors are highly aggressive with a poor prognosis. Metalothionein (MT) is a low-molecular intracellular protein, whose primary function is to regulate the homeostasis of heavy metals in many organisms. There are only few studies focusing on the molecular mechanisms of MT expression. Recent studies show its significant relations to carcinogenesis, spontaneous mutagenesis and efficiency of antitumor medicine. In previous studies, the increase of MT levels in cancer patients was proven. The aim of this work is to study MT as well as to increase the efficiency of malignant liver tumor diagnosis. METHODS: In our pilot study (2022-2023) we observed a group of 15 patients with hepatocellular carcinoma (diagnosis C220) and a group of 15 patients with hepatoblastoma (diagnosis C222). The control group included 20 healthy probands. We developed our own modified method for the analysis. Blood serum samples of the probands were denaturated (99 ˚C, 20 min). MT was determined by an electrochemical method. Obtained data were stored and processed in the laboratory information system QINSLAB. RESULTS: In denaturated blood serum samples, we obtained voltametric curves of MT. We determined concentrations of MT by evaluating the area under the curve (AUC). To differentiate normal and abnormal concentrations of MT, blood samples of healthy probands were used (N = 20), with the average MT levels of 2.0 ± 1.3 µg/L and median 1.9 µg/L. In patients diagnosed with HCC, the average MT levels were 9.1 ± 6.5 µg/L and median 9.0 µg/L. The receiver operating characteristic (ROC) analysis showed AUC 0.864 (95% CI 0.736-0.992), sensitivity 0.74 and specificity 0.75. In patients diagnosed with hepatoblastoma, the average MT concentrations measured were 11.5 ± 7.5 µg/L and the median was 10.9 µg/L. The ROC analysis displayed AUC 0.868 (95% CI 0.751-0.993), sensitivity 0.84 and specificity 0.86. The correlation analysis showed correlation between MT and carcinoembryonic antigen (CEA) (r = 0.99), uric acid (r = -0.86) and potassium ions (r = -0.94). CONCLUSION: In this pilot study, we observed the association of MT levels in healthy probands and malignant liver tumor patients. Many previous studies show that MT concentrations are increasing as the illness progresses. We assume that this increase is connected to the high metabolic activity of cancer cells. This study will continue with collecting a larger number of samples.
- Klíčová slova
- Brdička’s reaction, biomarker, cancer, malignant tumor, nanomedicine, targeted therapy,
- MeSH
- hepatoblastom krev MeSH
- hepatocelulární karcinom * krev patologie MeSH
- lidé MeSH
- metalothionein * krev MeSH
- nádorové biomarkery * krev MeSH
- nádory jater * krev MeSH
- pilotní projekty MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- metalothionein * MeSH
- nádorové biomarkery * MeSH
- MeSH
- cirkulující nádorová DNA * krev analýza MeSH
- lékařská onkologie metody MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory * krev diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
- Názvy látek
- cirkulující nádorová DNA * MeSH
- nádorové biomarkery MeSH