Current diagnostic tools used in clinical practice such as transvaginal ultrasound, CA 125, and HE4 are not sensitive and specific enough to diagnose OC in the early stages. A lack of early symptoms and an effective asymptomatic population screening strategy leads to a poor prognosis in OC. New diagnostic and screening methods are urgently needed for early OC diagnosis. Liquid biopsies have been considered as a new noninvasive and promising method, using plasma/serum, uterine lavage, and urine samples for early cancer detection. We analyzed recent studies on molecular biomarkers with specific emphasis on liquid biopsy methods and diagnostic efficacy for OC through the detection of circulating tumor cells, circulating cell-free DNA, small noncoding RNAs, and tumor-educated platelets.

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.

Ovarian cancer (OC) is the fifth leading cause of women’s death from cancers. The high mortality rate is attributed to the late presence of the disease and the lack of modern diagnostic tools, including molecular biomarkers. Moreover, OC is a highly heterogeneous disease, which contributes to early treatment failure. Thus, exploring OC molecular mechanisms could significantly enhance our understanding of the disease and provide new treatment options. Chromatin remodeling complexes (CRCs) are ATP-dependent molecular machines responsible for chromatin reorganization and involved in many DNA-related processes, including transcriptional regulation, replication, and reparation. Dysregulation of chromatin remodeling machinery may be related to cancer development and chemoresistance in OC. Some forms of OC and other gynecologic diseases have been associated with mutations in specific CRC genes. Most notably, ARID1A in endometriosis-related OC, SMARCA4, and SMARCB1 in hypercalcemic type small cell ovarian carcinoma (SCCOHT), ACTL6A, CHRAC1, RSF1 amplification in high-grade serous OC. Here we review the available literature on CRCs’ involvement in OC to improve our understanding of its development and investigate CRCs as possible biomarkers and treatment targets for OC.

Background and Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune, multi-factorial disease, in which environmental and genetic factors play a major role. RA is possibly linked to vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms, and research demonstrates that FokI variant susceptibility is associated with increased disease risk among Caucasians. The aim of this study was to evaluate vitamin D deficiency prevalence and its correlation to RA clinical parameters, and to determine the possible association of VDR gene polymorphisms and RA susceptibility in the Lithuanian population. Materials and Methods: Overall, 206 RA patients and 180 age- and sex-matched healthy controls were enrolled at Vilnius University Hospital Santaros Klinikos after informed consent was obtained. The disease activity score 28 C-reactive protein (DAS28 CRP), rheumatoid arthritis impact of disease (RAID) score, and health assessment questionnaire (HAQ) were recorded in RA patients, and 25(OH)D serum levels were evaluated by chemiluminescent microparticle immunoassay for all subjects. Four VDR gene polymorphisms, BsmI, FokI, ApaI, and TaqI, were assessed using real-time PCR instruments and genotyping assays in both groups. Results: The study registered a high prevalence of 25(OH)D deficiency (<50 nmol/L) in RA patients (61.55% (n = 127)). The mean serum concentration in RA patients (44.96 ± 21.92 (nmol/L)) was significantly lower than in the healthy controls (54.90 ± 22.82 (nmol/L)), p < 0.0001. A significant inverse correlation between vitamin D level, DAS28 CRP, and HAQ scores was confirmed in RA patients, with p < 0.05. Still, there was no significant association between the overall risk of RA disease for any allele or genotype of the four VDR loci tested. Conclusions: The study confirmed that vitamin D deficiency is prevalent among RA patients and the 25(OH)D level is significantly lower compared with healthy controls. Lower vitamin D concentration was related with increased disease activity and disability scores. However, genetic analysis of four VDR polymorphisms did not confer the susceptibility to RA in Lithuanian population.

The spatial distribution of tumor infiltrating lymphocytes (TILs) defines several histologically and clinically distinct immune subtypes—desert (no TILs), excluded (TILs in stroma), and inflamed (TILs in tumor parenchyma). To date, robust classification of immune subtypes still requires deeper experimental evidence across various cancer types. Here, we aimed to investigate, define, and validate the immune subtypes in melanoma by coupling transcriptional and histological assessments of the lymphocyte distribution in tumor parenchyma and stroma. We used the transcriptomic data from The Cancer Genome Atlas melanoma dataset to screen for the desert, excluded, and inflamed immune subtypes. We defined subtype-specific genes and used them to construct a subtype assignment algorithm. We validated the two-step algorithm in the qPCR data of real-world melanoma tumors with histologically defined immune subtypes. The accuracy of a classifier encompassing expression data of seven genes (immune response-related: CD2, CD53, IRF1, and CD8B; and stroma-related: COL5A2, TNFAIP6, and INHBA) in a validation cohort reached 79%. Our findings suggest that melanoma tumors can be classified into transcriptionally and histologically distinct desert, excluded, and inflamed subtypes. Gene expression-based algorithms can assist physicians and pathologists as biomarkers in the rapid assessment of a tumor immune microenvironment while serving as a tool for clinical decision making.

This study aimed at analyzing the DNA methylation pattern and TP53 mutation status of intrinsic breast cancer (BC) subtypes for improved characterization and survival prediction. DNA methylation of 17 genes was tested by methylation-specific PCR in 116 non-familial BRCA mutation-negative BC and 29 control noncancerous cases. At least one gene methylation was detected in all BC specimens and a 10-gene panel statistically significantly separated tumors from noncancerous breast tissues. Methylation of FILIP1L and MT1E was predominant in triple-negative (TN) BC, while other BC subtypes were characterized by RASSF1, PRKCB, MT1G, APC, and RUNX3 hypermethylation. TP53 mutation (TP53-mut) was found in 38% of sequenced samples and mainly affected TN BC cases (87%). Cox analysis revealed that TN status, age at diagnosis, and RUNX3 methylation are independent prognostic factors for overall survival (OS) in BC. The combinations of methylated biomarkers, RUNX3 with MT1E or FILIP1L, were also predictive for shorter OS, whereas methylated FILIP1L was predictive of a poor outcome in the TP53-mut subgroup. Therefore, DNA methylation patterns of specific genes significantly separate BC from noncancerous breast tissues and distinguishes TN cases from non-TN BC, whereas the combination of two-to-three epigenetic biomarkers can be an informative tool for BC outcome predictions.