MicroRNA (miRNA) profiling represents a promising source of cancer-related biomarkers. miRNA signatures are specific for each cancer type and subgroups of patients with diverse treatment sensitivity. Yet this miRNA potential has not been satisfactorily explored in rectal cancer (RC). The aim of the study was to identify the specific miRNA signature with clinical and therapeutic relevance for RC. Expressions of 2555 miRNA were examined in 20 pairs of rectal tumors and matched non-malignant tissues by 3D-Gene Toray microarray. Candidate miRNAs were validated in an independent cohort of 100 paired rectal tissues and in whole plasma and exosomes of 100 RC patients. To study the association of miRNA profile with therapeutic outcomes, plasma samples were taken repeatedly over a time period of 1 year reflecting thus patients' treatment responses. Finally, the most prominent miRNAs were investigated in vitro for their involvement in cell growth. We identified RC-specific miRNA signature that distinguishes responders from non-responders to adjuvant chemotherapy. A predominant part of identified miRNAs was represented by the members of miR-17/92 cluster. Upregulation of miRNA-17, -18a, -18b, -19a, -19b, -20a, -20b and -106a in tumor was associated with higher risk of tumor relapse and their overexpression in RC cell lines stimulated cellular proliferation. Examination of these miRNAs in plasma exosomes showed that their levels differed between RC patients and healthy controls and correlated with patient's treatment response. miRNAs from miR-17/92 cluster represent a non-invasive biomarker to predict posttreatment prognosis in RC patients.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• lidé MeSH
• mikro RNA genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádorové buněčné linie MeSH
• nádory rekta farmakoterapie   genetika   mortalita   MeSH
• proliferace buněk genetika   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• stanovení celkové genové exprese MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

INTRODUCTION: Peritoneal tumor seeding is a common form of recurrence after gastric cancer surgery. The finding of free tumor cells and/or elevation of tumor markers in the peritoneal fluid could predict intraperitoneal tumor recurrence. The results of these examination can be used for indication of aggressive treatment modalities such as hyperthermic intraperitoneal chemotherapy (HIPEC). MATERIAL AND METHODS: We have operated on 105 patients suffering from gastric cancer. The control group consisted of 12 patients without malignant disease. Peritoneal lavage fluid or ascites was collected immediately after laparotomy and examined by cytology and biochemistry (levels of carcinoembryonic antigen (CEA) and Ca 19-9). Sensitivity, specificity, stage correlation and overall survival were observed. RESULTS: Elevation of tumor markers or the finding of free intraperitoneal tumor cells predicts recurrence. The prognosis of these patients is same as in stage IV TNM classification with median survival time less than 1 year (p = 0.713). Patients with negative cytology have median survival time 5 years contrary to them with positive cytology (p < 0.001). Sensitivity of the cytology was 34% and specificity was 85%. Sensitivity of biochemistry was 53% (combination of both markers) and specificity was 100%. CONCLUSIONS: This study confirms the importance of peritoneal fluid examination for the prognosis. We cannot recommend routine use as an indicator for HIPEC due to low sensitivity, but the result of cytological examination is an independent factor for patient survival.

• Publikační typ
• časopisecké články MeSH

AIM: The aim of the present study is to address a genome-wide search for novel methylation biomarkers in the rectal cancer (RC), as only scarce information on methylation profile is available. MATERIALS & METHODS: We analyzed methylation status in 25 pairs of RC and adjacent healthy mucosa using the Illumina Human Methylation 450 BeadChip. RESULTS: We found significantly aberrant methylation in 33 genes. After validation of our results by pyrosequencing, we found a good agreement with our findings. The BPIL3 and HBBP1 genes resulted hypomethylated in RC, whereas TIFPI2, ADHFE1, FLI1 and TLX1 were hypermethylated. An external validation by TCGA datasets confirmed the results. CONCLUSION: Our study, with external validation, has demonstrated the feasibility of using specific methylated DNA signatures for developing biomarkers in RC.

• MeSH
• alkoholoxidoreduktasy genetika   MeSH
• epigeneze genetická * MeSH
• homeodoménové proteiny genetika   MeSH
• lidé MeSH
• metylace DNA * MeSH
• mitochondriální proteiny genetika   MeSH
• nádorové biomarkery genetika   MeSH
• nádory rekta genetika   MeSH
• protoonkogenní protein c-fli-1 genetika   MeSH
• protoonkogenní proteiny genetika   MeSH
• střevní sliznice metabolismus   MeSH
• transportní proteiny genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH