Background: Beta-adrenergic signalling plays an important role in several cancer-related processes, including angiogenesis. The impact of beta-blocker use on prognosis of cancer patients treated with antiangiogenic agents is unclear. The aim of this study was to evaluate the association between the incidental use of beta-blockers and the outcomes of patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based therapy. Methods: Clinical data from 514 mCRC patients treated with bevacizumab between 2005 and 2019 were analysed retrospectively. The association of progression-free survival (PFS) and overall survival (OS) with the incidental use of beta-blockers and other common antihypertensive drugs was assessed. Results: The median PFS and OS for patients using beta-blockers was 11.40 (95% confidence interval (CI) 10.10–13.61) months and 26.8 (95% CI 22.2–32.2) months compared with 8.30 (95% CI 7.80–9.57) and 21.0 (95% CI 17.8–23.8) months for patients not using beta-blockers (p = 0.006 and p = 0.009, respectively). In the Cox multivariate analysis, the use of beta-blockers was a significant factor predicting both PFS (hazard ratio (HR) = 0.763 (95% CI 0.606–0.960), p = 0.021) and OS (HR = 0.730 (95% CI 0.560–0.951), p = 0.020). Conclusions: The results of the present retrospective study suggest that there is a significant association between the use of beta-blockers and favourable outcomes of mCRC patients treated with bevacizumab-based therapy.

Although colorectal cancer (CRC) is the third most frequent cause of cancer related death in Europe, clinically relevant biomarkers for therapy guidance and prognosis are insufficiently reliable. Long non-coding RNAs (lncRNAs) are RNAs over 200 nucleotides long that are not translated into proteins but can influence biological processes. There is emerging evidence for their involvement in solid cancer as oncogenes, tumour suppressors or regulators of cell proliferation and metastasis development. The goal of this study was to evaluate the prognostic effect of selected lncRNAs in a retrospective study on CRC patients from the Czech Republic. We used a quantitative PCR approach to measure the expression in paired non-malignant and tumour tissue samples of CRC patients of nine lncRNAs previously shown to be involved in cancer progression—ANRIL, CCAT1, GAS5, linc-ROR, MALAT1, MIR155HG, PCAT1, SPRY4-IT1 and TUG1. Associations between expression and expression ratios and clinical characteristics and survival were assessed by using univariable Cox proportional hazards models, Kaplan-Meier estimations with the Gehan-Wilcoxon test, the Mann-Whitney U test, the Kruskal-Wallis test and Spearman’s correlations. A comparison of expression in tumour tissue (TT) and non-malignant mucosa tissue (MT) showed significant upregulation of CCAT1 and linc-ROR in TT (p < 0.001 and p = 0.001, respectively) and downregulation of ANRIL, MIR155HG and MALAT1 (p = 0.001, p = 0.010, p = 0.001, respectively). Linc-ROR was significantly associated with the presence of synchronous metastases (p = 0.033). For individual tissue types, lower MIR155HG expression in TT was correlated with both shorter overall survival (p = 0.008) and shorter disease-free survival (p = 0.040). In MT, expression ratios of CCAT1/ANRIL and CCAT1/MIR155HG were associated with overall survival (p = 0.005 and p = 0.006, respectively). Our results revealed that changes in expression of lncRNAs between MT and TT hold potential to be used as prognostic biomarkers in CRC patients. Moreover, the ratios of CCAT1 to ANRIL and MIR155HG in MT also exhibit potential for prognosis assessment without tumour sampling. Our results also indicate that cancer progression is associated with detrimental system-wide changes in patient tissue, which might govern patient survival even after successful elimination of tumour or cancerous cells.

Background. Abdominal aortic aneurysms (AAA) are relatively frequent in elderly population, and their ruptures are related with high mortality rate. There are no actually used laboratory markers predicting the AAA development, course, and rupture. MicroRNAs are small noncoding molecules involved in posttranscriptional gene expression regulation, influencing processes on cell and tissue levels, and are actually in focus due to their potential to become diagnostic or prognostic markers in various diseases. Methods. Tissue samples of AAA patients and healthy controls were collected, from which miRNA was isolated. Microarray including the complete panel of 2549 miRNAs was used to find expression miRNA profiles that were analysed in three subgroups: small (N = 10) and large (N = 6) aneurysms and healthy controls (N = 5). Fold changes between expression in aneurysms and normal tissue were calculated including corresponding p values, adjusted to multiple comparisons. Results. Six miRNAs were found to be significantly dysregulated in small aneurysms (miR-7158-5p, miR-658, miR-517-5p, miR-122-5p, miR-326, and miR-3180) and 162 in large aneurysms, in comparison with the healthy control. Ten miRNAs in large aneurysms with more than two-fold significant change in expression were identified: miR-23a-3p, miR-24-3p, miR-27a-3p, miR-27b-3p, miR-30d-5p, miR-193a-3p, miR-203a-3p, miR-365a-3p, miR-4291, and miR-3663-3p and all, but the last one was downregulated in aneurysmal walls. Conclusion. We confirmed some previously identified miRNAs (miR-23/27/24 family, miR-193a, and miR-30) as associated with AAA pathogenesis. We have found other, yet in AAA unidentified miRNAs (miR-203a, miR-3663, miR-365a, and miR-4291) for further analyses, to investigate more closely their possible role in pathogenesis of aneurysms. If their role in AAA development is proved significant in future, they can become potential markers or treatment targets.