Abstract. Colorectal cancer (CRC) is one of the most frequent malignant diseases in the world. Metastatic spread of the cancer to the lymph nodes is a crucial factor for progression and therapeutic management of the disease. We analysed gene expression profiles of CRC patiens by lowdensity cancer-focused oligonucleotide microarrays to identify new predictive markers of the extent of the disease and for better understanding of CRC progression. Relative expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 20 tumor samples. Statistical analysis of gene expression data identified 3 genes (HSP110, HYOU1 and TCTP) significantly up-regulated in primary tumors of patients who developed lymph node metastasis. We have shown, for the first time, that up-regulation HSP110 and HYOU1 expression is associated with lymph node involvement in CRC. We validated the differences in HSP110 expression in an independent group of 30 patients of all clinical stages by real-time PCR. We identified significant up-regulation of HSP110 expression in colorectal tumors compared to adjacent non-tumoral tissue (p<0.0003). We observed significant differences of HSP110 gene expression between metastatic and localized disease (p=0.031) and negative trend of HSP110 gene expression and overall survival of CRC patients. We suggest that HSP110 gene is a promising molecular predictor in CRC. IntroductionColorectal cancer (CRC) is one of the most frequent malignant diseases in the world. With the incidence rate ~78 per 100,000 people, the Czech Republic is a country with one of the highest incidence of CRC in the world and the highest in Europe (1). The prognosis of these patients depends largely on the extent of the disease and a possibility of curative surgical intervention which is feasible only in patients with disease limited to the primary tumor and regional lymph nodes. Spread of the cancer to lymph nodes has been considered a crucial factor for progression and further therapeutic management of the disease. While in the case of clinical stage I and IV, the prognostic significance of the TNM classification is evident, for the group of patients diagnosed at stages II (without dissemination to regional lymph nodes) and III (with dissemination to lymph nodes) the prognostic information of clinical stage is much lower. The fact, that 30% of patients with clinical stage II of CRC will progress within five years and only 45% of the patients with clinical stage III will reach a 5-year survival, although undergoing radical surgery, implies that recent staging of CRC based on TNM classification is not optimal and failed for a significant proportion of non-advanced CRC patients. This situation is caused by two factors: firstly, understaging of regional lymph node status for the reason of insufficient number of resected and/or examined lymph nodes, secondly, the TNM classification does not include biological characteristics and predictors of tumor behaviour. Multicentric studies ba...
Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.
Abstract:To compare preoperative intestinal trefoil factor 3 (TFF3), allograft inflammatory factor-1 (AIF-1) and calgizzarin (S100-A11) serum levels in patients with endometrial cancer, endometrial hyperplasia and in healthy female controls. Serum levels of TFF3, S100-A11 and AIP-1 were analyzed in 98 consecutive patients with histologically verified endometrial cancer, in 43 patients with endometrial hyperplasia diagnosed during hysteroscopy and 24 controls with benign disease. Results were correlated with urinary neopterin/creatinine ratio, serum kynurenine, tryptophan, retinol, alpha-tocopherol, vitamin D, citrulline, C-reactive protein, interleukin-6 and clinical characteristics. S100-A11, and AIF-1 levels were higher in endometrial hyperplasia patients than in controls, and also significantly higher in endometrial cancer than in patients with endometrial hyperplasia. Serum concentrations of TFF3 and S100-A11 were associated with tumor stage and lymph node status. TFF3 exhibited positive correlation with age, IL-6, vitamin D, kynurenine, urinary neopterin/creatinine ratio and kynurenine/tryptophan ratio. S100-A11, as well as AIF-1 correlated positively with Il-6 and TFF3. TFF3, S100-A11 and AIF-1 represent potential biomarkers in patients with endometrial cancer. TFF3 and S100-A11 increase with tumor stage and lymph node involvement, reflecting higher tumor mass that is also associated with increased concentration of biomarkers of immune dysfunction.
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