Colorectal cancer (CRC) belongs to the most common cancers. The liver is a predominant site of CRC dissemination. Novel biomarkers for predicting the survival of CRC patients with liver metastases (CLM) undergoing metastasectomy are needed. We examined KRAS mutated circulating cell-free tumor DNA (ctDNA) in CLM patients as a prognostic biomarker, independently or in combination with carcinoembryonic antigen (CEA). Thereby, a total of 71 CLM were retrospectively analyzed. Seven KRAS G12/G13 mutations was analyzed by a ddPCR™ KRAS G12/G13 Screening Kit on QX200 Droplet Digital PCR System (Bio-Rad Laboratories, Hercules, CA, USA) in liver metastasis tissue and preoperative and postoperative plasma samples. CEA were determined by an ACCESS CEA assay with the UniCel DxI 800 Instrument (Beckman Coulter, Brea, CA, USA). Tissue KRAS positive liver metastases was detected in 33 of 69 patients (47.8%). Preoperative plasma samples were available in 30 patients and 11 (36.7%) were KRAS positive. The agreement between plasma- and tissue-based KRAS mutation status was 75.9% (22 in 29; kappa 0.529). Patients with high compared to low levels of preoperative plasma KRAS fractional abundance (cut-off 3.33%) experienced shorter overall survival (OS 647 vs. 1392 days, p = 0.003). The combination of high preoperative KRAS fractional abundance and high CEA (cut-off 3.33% and 4.9 µg/L, resp.) best predicted shorter OS (HR 13.638, 95%CI 1.567–118.725) in multivariate analysis also (OS HR 44.877, 95%CI 1.59–1266.479; covariates: extend of liver resection, biological treatment). KRAS mutations are detectable and quantifiable in preoperative plasma cell-free DNA, incompletely overlapping with tissue biopsy. KRAS mutated ctDNA is a prognostic factor for CLM patients undergoing liver metastasectomy. The best prognostic value can be reached by a combination of ctDNA and tumor marker CEA.
In 2019, the EPMA celebrated its 10th anniversary at the 5th World Congress in Pilsen, Czech Republic. The history of the International Professional Network dedicated to Predictive, Preventive and Personalised Medicine (PPPM / 3PM) is rich in achievements. Facing the coronavirus COVID-19 pandemic it is getting evident globally that the predictive approach, targeted prevention and personalisation of medical services is the optimal paradigm in healthcare demonstrating the high potential to save lives and to benefit the society as a whole. The EPMA World Congress Supplement 2020 highlights advances in 3P medicine.
There is an ongoing debate as to whether SARS-CoV-2 antibodies can be found in patients who have recovered from COVID-19 disease. Currently, there is no consensus on whether the antibodies, if present, are protective. Our regular measurements of SARS-CoV-2 antibodies, starting in July 2020, have provided us with the opportunity of becoming acquainted with the five different immunoassays. A total of 149 patients were enrolled in our study. We measured the samples using each immunoassay, then performing a virus neutralization test and comparing the results of SARS-CoV-2 antibodies with this test. We observed that the production of neutralizing antibodies is age-dependent. Elderly patients have a higher proportion of high neutralizing titers than young patients. Based on our results, and in combination with the literature findings, we can conclude that the serological SARS-CoV-2 antibody measurement is a helpful tool in the fight against COVID-19. The assays can provide information about the patient’s previous contact with the virus. Anti-spike protein assays correlate well with the virus neutralization test and can be used in the screening of potential convalescent plasma donors.
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.
Background: Circulating microRNAs (miRNAs) are promising non-invasive biomarkers for colorectal cancer (CRC). The aim of the present study was to evaluate the role of five circulating miRNAs e miRNA-618, miRNA-26a-1, miRNA-15b-5p, miRNA-200c, miRNA-203a-3p which are involved in key cell signal processes in tumors such as proliferation, migration, and apoptosis. These miRNAs are thoroughly investigated in tumor tissue, but little is known regarding their levels of expression in the blood of patients with CRC.Methods: 97 patients with colorectal metastatic disease before starting the chemotherapy and 80 healthy controls were investigated. miRNAs were isolated from serum samples by commercial kit. cDNA was generated from each sample. All miRNA data were analyzed by normalization using U6 as a constitutively expressed endogenous control. qRT-PCR was performed and the relative expression of each miRNAs was calculated by using 2 -DDCt method.Results: Serum miRNA-618, miRNA-26a-1, miRNA-15b-5p, miRNA-200c, and miRNA-203a-3p were significantly overexpressed in CRC patients. Among all investigated miRNAs only two of them were associated with CRC patient survival. Patients with low expression levels of circulating miRNA-618 had significantly shorter median overall survival (OS) of 14 months (95% CI, 8.63-19.37) as compared with those with high expression -21 months (95% CI, 14.36-27.64) (p¼0.003). Also, patients with low levels of miRNA-203a-3p had a significantly shorter median OS of 14 months (95% CI, 8.81-19,19) compared with 20 months in patients with higher expression in the blood (95% CI, 17.05-22.95) (p¼0.012). In addition, Cox proportional hazards regression model showed that low levels of miRNA-618 and miRNA-203a-3p expressions were associated with a shorter OS, HR¼2.02 (95% CI, 1.24-3.29; p¼0.005) and HR¼1.77 (95% CI, 1.08-2.91; p¼0.025), respectively. Conclusion:Our data suggest that only expression levels of anti-oncogenic miRNA-618 and miRNA-203a-3p in sera could be useful as non-invasive prognostic biomarkers in CRC patients.Legal entity responsible for the study: The authors.
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