CONTEXT: Many liquid biomarkers have entered clinical practice with the praise to improve the detection of clinically significant prostate cancer (csPCa), helping avoid unnecessary prostate biopsies. OBJECTIVE: We aimed to assess the diagnostic accuracy of multianalyte biomarkers for csPCa detection using multiple thresholds. EVIDENCE ACQUISITION: A comprehensive literature search was done through PubMed, Web of Science, and Scopus in March 2023 for prospective and retrospective studies reporting the diagnostic performance of liquid biomarkers for detecting csPCa. The outcomes of interest were the diagnostic performance of liquid biomarkers for csPCa detection and identification of optimal thresholds for each biomarker. EVIDENCE SYNTHESIS: Overall, 49 studies were eligible for this meta-analysis. Using each representative threshold based on the Youden Index, the pooled sensitivity and specificity for detecting csPCa were 0.85 and 0.37 for prostate cancer gene 3 (PCA3), 0.85 and 0.52 for prostate health index (PHI), 0.87 and 0.58 for four kallikrein (4K), 0.82 and 0.56 for SelectMDx, 0.85 and 0.54 for ExoDx, and 0.82 and 0.59 for mi prostate score (MPS), respectively. The diagnostic odds ratio was highest for 4K (8.84), followed by MPS (7.0) and PHI (6.28). According to the meta-analysis incorporating multiple thresholds, the corresponding sensitivity was 0.77 for 4K, 0.69 for PHI, and 0.63 for PCA3; specificity was 0.72 for PHI, 0.70 for 4K, and 0.69 for PCA3. CONCLUSIONS: Regarding the detection of csPCa, 4K had the highest diagnostic performance among the commercial liquid biomarkers. Based on the optimal thresholds calculated by the present meta-analysis, 4K had the highest sensitivity and PHI had the highest specificity for detecting csPCa. Nevertheless, clinical decision-making requires combination strategies between liquid and imaging biomarkers. PATIENT SUMMARY: Novel biomarkers for prostate cancer detection were useful for more accurate diagnosis of clinically significant prostate cancer to avoid unnecessary biopsies.
- MeSH
- lidé MeSH
- nádorové biomarkery * krev MeSH
- nádory prostaty * diagnóza krev MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
Východiska: Zhoubné nádory jater jsou agresivní a mají špatnou prognózu přežití. Metalothionein (MT) je nízkomolekulární intracelulární protein, jehož primární funkcí je udržení homeostázy těžkých kovů v živých organizmech. Molekulární mechanizmus exprese MT je velmi málo prostudován. Nedávné výzkumy ukazují na jeho významný vztah ke karcinogenezi, spontánní mutagenezi a účinnosti protinádorových léčiv. Již v předchozích studiích bylo dokázáno, že hladiny MT stoupají u nádorového onemocnění. Cílem naší práce bylo studium MT za účelem zvýšení efektivity diagnostiky zhoubných nádorů jater. Metody: V pilotní studii (2022–2023) byla sledována skupina 15 pacientů s hepatocelulárním karcinomem (hepatocellular carcinoma – HCC, diagnóza C220) a skupina 15 pacientů s hepatoblastomem (diagnóza C222). Kontrolní skupina byla vybrána ze zdravých probandů (n = 20). Pro analýzu byla použita námi vyvinutá modifikovaná metoda. Vzorky krevních sér probandů byly tepelně denaturovány (99 ̊C, 20 min). MT byl stanoven pomocí elektrochemie. Získaná data byla uložena a zpracována v laboratorním informačním systému QINSLAB. Výsledky: U vzorků denaturovaných krevních sér byly získány voltametrické křivky MT. Stanovením plochy pod křivkou (area under the curve – AUC) byly vypočteny koncentrace MT. Pro porovnání normální a abnormální hladiny MT byla použita kontrolní séra zdravých probandů (n = 20) se zjištěným průměrným množstvím MT 2,0 ± 1,3 μg/l a mediánem 1,9 μg/l. U skupiny pacientů s HCC bylo zjištěno průměrné množství MT 9,1 ± 6,5 μg/l a medián 9,0 μg/l. Tzv. receiver operating characteristic (ROC) analýza ukázala AUC 0,864 (95% CI 0,736–0,992), senzitivitu 0,74 a specificitu 0,75. U pacientů s hepatoblastomem bylo zjištěno průměrné množství MT 11,5 ± 7,5 μg/l a medián 10,9 μg/l. ROC analýza ukázala AUC 0,868 (95% CI 0,751–0,993), senzitivitu 0,84 a specificitu 0,86. V korelační analýze byla pozorována korelace MT ke karcinoembryonálnímu antigenu (CEA) (r = 0,99), kyselině močové (r = −0,86) a iontům draslíku (r = −0,94). Závěr: V této pilotní studii se podařilo sledovat pravděpodobnou asociaci hladiny MT u probandů se zhoubnými nádory jater. Z publikovaných prací je známo, že hladiny MT jsou dlouhodobě zvýšené a předpokládáme, že souvisí se zvýšenou metabolickou aktivitou nádorových buněk. Studie bude dále pokračovat na větším souboru pacientů.
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.
- MeSH
- elektrochemické techniky klasifikace metody MeSH
- hepatoblastom krev patologie MeSH
- hepatocelulární karcinom krev patologie MeSH
- lidé MeSH
- metalothionein * analýza krev MeSH
- nádorové biomarkery analýza krev MeSH
- nádory jater * diagnóza farmakoterapie krev MeSH
- pilotní projekty MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem 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
Background: The second-leading source of neoplasm-related death and a primary factor in gastrointestinal cancer, colorectal cancer (CCR) affects both genders globally. Poor eating behaviours, tobacco, an intestinal inflammatory disorder, swellings, inherited characteristics, and the elderly all increase the threat of acquiring this malignancy. The illness is more hostile in patients detected at earlier ages, although 90% of patients with colorectal tumours are older than 50, with a median oldness of 64 years. American Cancer Association estimates that it caused more than 49,700 fatalities in 2015.Objectives: Study the correlation of midkine with carcinoembryonic antigen (CEA), liver function tests, and white blood cell count in patients with colorectal carcinoma.Methods: The serum midkine and CEA of all subjects were measured by the ELISA technique, Liver enzymes were measured by colourimetric methods and neutrophils, and lymphocytes were measured by an Electrical Impedance Cell Counting method (automated machine).Conclusion: The study results of the correlation between serum midkine and other parameters in colorectal carcinoma patients show a significant positive correlation of midkine with CEA, liver enzyme, neutrophils, and lymphocytes.
- MeSH
- dospělí MeSH
- hematologické testy metody MeSH
- jaterní testy metody MeSH
- karcinoembryonální antigen krev MeSH
- kolorektální nádory * krev MeSH
- leukocyty MeSH
- lidé středního věku MeSH
- lidé MeSH
- midkin * krev MeSH
- nádorové biomarkery krev MeSH
- prognóza MeSH
- statistika jako téma MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
BACKGROUND: The European Association of Urology guidelines include the lutetium-177 (177Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers. OBJECTIVE: To assess the performance of 177Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study including 233 patients with mCRPC treated with 177Lu PSMA in eight high-volume European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and clinical parameters during and after 177Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ2 and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models. RESULTS AND LIMITATIONS: A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of 177Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of 177Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046). CONCLUSIONS: 177Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice. PATIENT SUMMARY: 177Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.
- MeSH
- antigeny povrchové metabolismus MeSH
- glutamátkarboxypeptidasa II metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- ligandy MeSH
- lutecium * terapeutické užití MeSH
- metastázy nádorů MeSH
- nádorové biomarkery krev MeSH
- nádory prostaty rezistentní na kastraci * patologie radioterapie farmakoterapie MeSH
- prostatický specifický antigen krev MeSH
- radionuklidy terapeutické užití 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
- multicentrická studie MeSH
- pozorovací studie MeSH
- Geografické názvy
- Evropa MeSH
Multiple myeloma (MM) is the second most prevalent hematological malignancy, characterized by infiltration of the bone marrow by malignant plasma cells. Extramedullary disease (EMD) represents a more aggressive condition involving the migration of a subclone of plasma cells to paraskeletal or extraskeletal sites. Liquid biopsies could improve and speed diagnosis, as they can better capture the disease heterogeneity while lowering patients' discomfort due to minimal invasiveness. Recent studies have confirmed alterations in the proteome across various malignancies, suggesting specific changes in protein classes. In this study, we show that MALDI-TOF mass spectrometry fingerprinting of peripheral blood can differentiate between MM and primary EMD patients. We constructed a predictive model using a supervised learning method, partial least squares-discriminant analysis (PLS-DA) and evaluated its generalization performance on a test dataset. The outcome of this analysis is a method that predicts specifically primary EMD with high sensitivity (86.4%), accuracy (78.4%), and specificity (72.4%). Given the simplicity of this approach and its minimally invasive character, this method provides rapid identification of primary EMD and could prove helpful in clinical practice.
- MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom * krev diagnóza MeSH
- nádorové biomarkery krev MeSH
- senioři MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice metody MeSH
- tekutá biopsie metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Classical serum cancer biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), remain important tools in colorectal cancer (CRC) management for disease follow up. However, their sensitivity and specificity are low for diagnostic and prognostic evaluation. The aim of this study was to evaluate the potential of biomarkers reflecting biological activity of tumors - tissue polypeptide specific antigen (TPS), cytokeratin fragment 19 (CYFRA 21-1), thymidine kinase (TK), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGF-BP3) - together with the CEA and CA 19-9 in CRC diagnosis and prognosis. PATIENTS AND METHODS: This is a retrospective study including 148 CRC patients and 68 age-matched healthy subjects. Serum biomarkers were measured in pre-operative serum samples using immunoanalytical methods. The end-point for the diagnostic evaluation was the area under the receiving operating characteristic curve (AUC ROC) of the biomarkers. The end-point for the prognostic evaluation was overall survival. RESULTS: Serum levels of CEA, CA 19-9, TPS, and TK were significantly increased in CRC early-stage patients compared with healthy controls. Each of the studied biomarkers had AUC between 0.6 and 0.7. Analysis of survival demonstrated that the patients with CEA, CA 19-9, cytokeratin, and TK above optimal cut offs had significantly shorter survival. A multivariate analysis performed on all the study biomarkers resulted in the selection of CYFRA 21-1 as the best performing biomarker with hazard ratio 10.413. CONCLUSION: The combination of cytokeratins and thymidine kinase with classical cancer biomarkers enables the prediction of tumor aggressiveness and long-term prognosis.
- MeSH
- antigen CA-19-9 * krev MeSH
- antigeny nádorové krev MeSH
- dospělí MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- karcinoembryonální antigen * krev MeSH
- keratin-19 krev MeSH
- keratiny krev MeSH
- kolorektální nádory * krev diagnóza patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery * krev MeSH
- peptidy MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- thymidinkináza * krev 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
INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS: We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS: Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS: We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION: NCT04221347.
- MeSH
- časná detekce nádoru * metody MeSH
- dospělí MeSH
- hepatocelulární karcinom * krev diagnóza diagnostické zobrazování MeSH
- index tělesné hmotnosti MeSH
- jaterní cirhóza krev komplikace diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery krev MeSH
- nádory jater * krev diagnóza diagnostické zobrazování MeSH
- obezita * komplikace krev MeSH
- prediktivní hodnota testů MeSH
- Ramanova spektroskopie MeSH
- ROC křivka MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie 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.
- 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
