Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding.

BACKGROUND: MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer. METHODS: Fifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed. RESULTS: Both miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs. CONCLUSIONS: There was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.

Significance of blood serum catalase activity and malondialdehyde level for survival prognosis of ovarian cancer patients.

BACKGROUND AND OBJECTIVE: Several markers were found to be potential prognostic factors in ovarian cancer. Among markers resembling systemic changes in the host's organism are markers of the oxidative stress. In this study we attempted to analyze the oxidant and antioxidant parameters of ovarian cancer patients. MATERIALS AND METHODS: A total of 42 patients with newly diagnosed stages I-IV primary ovary cancer were examined. Level of malondialdehyde (MDA) and catalytic activity catalase (CAT) were determined spectrophotometrically. RESULTS: Significantly lower CAT (28.2±15.5 vs. 36.1±14.6nmol/L/min, P=0.019) activity and higher MDA levels (8.7±3.0 vs. 6.7±2.7nmol/L, P=0.002) were observed in cancer patients compared with healthy volunteers. Both variables were not confirmed as prognostic factors according to Kaplan-Meier survival estimates. CONCLUSIONS: MDA and CAT demonstrate oxidative stress in cancer patients: CAT activity was significantly lower and MDA levels higher in cancer patients compared to healthy controls. These variables were not confirmed to be prognostic factors in ovarian cancer, possibly due to small size of the study group.

Relationship of MDA plasma concentrations to long-term survival of breast cancer patients.

AIMS AND BACKGROUND: Malondialdehyde (MDA) is a product of polyunsaturated fatty acid oxidation. Changes in MDA concentrations have been found in patients with various types of cancer. The aim of this study was to analyze the relationship of MDA plasma concentrations to the long-term survival of patients with breast cancer. METHODS AND STUDY DESIGN: We conducted a retrospective study which included 106 patients at various disease stages (I - n = 2; II - n = 30; III - n = 51; IV - n = 23). Plasma MDA concentrations were measured at the time of diagnosis. Study participants were divided into groups according to age (<55 years vs ≥55 years), disease stage, and MDA concentration (<9 mmol/L vs ≥9 mmol/L). Survival rates between groups were compared using the Kaplan-Meier method. RESULTS: We found that higher MDA concentrations were associated with lower survival rates in stage I and II breast cancer. No significant association was found in patients with stage III and IV disease. Multivariate analysis showed that the MDA level was the only independent prognostic factor for patient survival in the total study group (hazard ratio 1.57, P = 0.03). CONCLUSION: MDA can be used as a prognostic factor in early stages of breast cancer.