Background and Objectives: The aim of this systematic review was to analyse which candidate genes were examined in genetic association studies and their association with major depressive disorder (MDD). Materials and Methods: We searched PUBMED for relevant studies published between 1 July 2012 and 31 March 2019, using combinations of keywords: “major depressive disorder” OR “major depression” AND “gene candidate”, “major depressive disorder” OR “major depression” AND “polymorphism”. Synthesis focused on assessing the likelihood of bias and investigating factors that may explain differences between the results of studies. For selected gene list after literature overview, functional enrichment analysis and gene ontology term enrichment analysis were conducted. Results: 141 studies were included in the qualitative review of gene association studies focusing on MDD. 86 studies declared significant results (p < 0.05) for 172 SNPs in 85 genes. The 13 SNPs associations were confirmed by at least two studies. The 18 genetic polymorphism associations were confirmed in both the previous and this systematic analysis by at least one study. The majority of the studies (68.79 %) did not use or describe power analysis, which may have had an impact over the significance of their results. Almost a third of studies (N = 54) were conducted in Chinese Han population. Conclusion: Unfortunately, there is still insufficient data on the links between genes and depression. Despite the reported genetic associations, most studies were lacking in statistical power analysis, research samples were small, and most gene polymorphisms have been confirmed in only one study. Further genetic research with larger research samples is needed to discern whether the relationship is random or causal. Summations: This systematic review had summarized all reported genetic associations and has highlighted the genetic associations that have been replicated. Limitations: Unfortunately, most gene polymorphisms have been confirmed only once, so further studies are warranted for replicating these genetic associations. In addition, most studies included a small number of MDD cases that could be indicative for false positive. Considering that polymorphism loci and associations with MDD is also vastly dependent on interpersonal variation, extensive studies of gene interaction pathways could provide more answers to the complexity of MDD.

Non-small cell cancer (NSCLC) has been identified with a great variation of mutations that can be surveyed during disease progression. The aim of the study was to identify and monitor lung cancer-specific mutations incidence in cell-free DNA as well as overall plasma cell-free DNA load by means of targeted next-generation sequencing. Sequencing libraries were prepared from cell-free DNA (cfDNA) isolated from 72 plasma samples of 41 patients using the Oncomine Lung cfDNA panel covering hot spot regions of 11 genes. Sequencing was performed with the Ion Torrent™ Ion S5™ system. Four genes were detected with highest mutation incidence: KRAS (43.9% of all cases), followed by ALK (36.6%), TP53 (31.7%), and PIK3CA (29.3%). Seven patients had co-occurring KRAS + TP53 (6/41, 14.6%) or KRAS + PIK3CA (7/41, 17.1%) mutations. Moreover, the mutational status of TP53 as well an overall cell-free DNA load were confirmed to be predictors of poor progression-free survival (HR = 2.5 [0.8–7.7]; p = 0.029 and HR = 2.3 [0.9–5.5]; p = 0.029, respectively) in NSCLC patients. In addition, TP53 mutation status significantly predicts shorter overall survival (HR = 3.4 [1.2–9.7]; p < 0.001). We demonstrated that TP53 mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.

(1) Background: DNA damage response (DDR) pathway gene mutations are detectable in a significant number of patients with metastatic castration-resistant prostate cancer (mCRPC). The study aimed at identification of germline and/or somatic DDR mutations in blood and urine samples from patients with mCRPC for correlation with responses to entire sequence of systemic treatment and survival outcomes. (2) Methods: DDR gene mutations were assessed prospectively in DNA samples from leukocytes and urine sediments from 149 mCRPC patients using five-gene panel targeted sequencing. The impact of DDR status on progression-free survival, as well as treatment-specific and overall survival, was evaluated using Kaplan–Meier curves and Cox regression. (3) Results: DDR mutations were detected in 16.6% of urine and 15.4% of blood samples. BRCA1, BRCA2, CHEK2, ATM and NBN mutations were associated with significantly shorter PFS in response to conventional androgen deprivation therapy and first-line mCRPC therapy with abiraterone acetate. Additionally, BRCA1 and BRCA2 mutation-bearing patients had a significantly worse response to radium-223. However, DDR mutation status was predictive for the favourable effect of second-line abiraterone acetate after previous taxane-based chemotherapy. (4) Conclusions: Our data confirm the benefit of non-invasive urine-based genetic testing for timely identification of high-risk prostate cancer cases for treatment personalization.

Background/Objectives: Early and accurate detection of postoperative complications (POCs) remains a major challenge in colorectal cancer (CRC) surgery, underscoring the need for reliable molecular biomarkers. This study evaluated whether plasma miR-21 and miR-181a can predict POCs following left-sided CRC resection. Methods: This longitudinal observational sub-study was conducted within a randomized controlled trial. Adult patients undergoing elective left-sided CRC resection were included. Plasma miR-21 and miR-181a levels were measured preoperatively and on postoperative day (POD) 6 using RT-qPCR. POCs were assessed according to Clavien–Dindo classification. Of 40 enrolled patients, 38 were included in the final analysis (15 with and 23 without postoperative complications). Discriminative performance was assessed using receiver operating characteristic analysis and correlations with inflammatory markers were evaluated. Results: No significant differences in plasma miR-21 or miR-181a levels were observed between groups at baseline or POD6 (all p > 0.05). Both biomarkers showed limited discriminative ability (AUC = 0.61 and 0.54, respectively), while a combined model of miR-181a + TNF-α improved performance (AUC = 0.76, 95% CI: 0.57, 0.94, p = 0.01). At baseline, miR-21 correlated strongly with miR-181a (ρ = 0.81, p < 0.001) and moderately inversely with TNF-α (ρ = −0.35, p = 0.043). Conclusions: MiR-21 or miR-181a measured at baseline or POD6 show limited predictive value for POCs after CRC surgery. Further studies would benefit from larger sample sizes and optimized sampling strategies that reflect possible early dynamic changes in these biomarkers.

Objectives: Acute pancreatitis (AP) is a painful and potentially life-threatening disorder, with no effective therapy available to date. Genome assessment shows promise as a potential method for predicting AP severity. We hypothesized that single-nucleotide polymorphisms (SNPs) and expression changes in heat shock protein 70 (HSP70) family genes may play a role in early prediction of AP severity. Methods: A total of 44 AP patients and 47 age- and sex-matched healthy controls were studied. Leukocyte-extracted total RNA and genomic DNA were used for HSPA1A and HSPA1L gene expression and genotyping in promoter regions ( HSPA1A : rs1008438 and HSPA1L : rs2227956) analyses, respectively. Results: No statistically significant differences were found between the genotypes of AP patients and controls; however, HSPA1A expression was 2-fold lower in AP. The decrease in expression was more evident in the mild and mild/moderate AP groups versus controls ( P =0.024 and 0.008, respectively). HSPA1L expression in AG versus AA carriers was higher in the entire cohort ( P =0.014) and markedly differed between AP patients ( P =0.001). Also, HSPA1L expression was the highest in severe AG cases and significantly differed from AA genotype carriers ( P =0.005). Conclusions: We suggest that HSP70 family gene expression may be a valuable marker for predicting disease severity in AP.