Aberrant expression of certain genes and microRNAs (miRNAs) has been shown to drive cancer development and progression, thus the modification of aberrant gene and miRNA expression presents an opportunity for therapeutic targeting. Ectopic modulation of a single dysregulated miRNA has the potential to revert therapeutically unfavorable gene expression in cancer cells by targeting multiple genes simultaneously. Although the use of noncoding RNA-based cancer therapy is a promising approach, the lack of a feasible delivery platform for small noncoding RNAs has hindered the development of this therapeutic modality. Recently, however, there has been an evolution in RNA nanotechnology, in which small noncoding RNA is loaded onto nanoparticles derived from the pRNA-3WJ viral RNA motif of the bacteriophage phi29. Preclinical studies have shown the capacity of this technology to specifically target tumor cells by conjugating these nanoparticles with ligands specific for cancer cells and resulting in the endocytic delivery of siRNA and miRNA inhibitors directly into the cell. Here we provide a systematic review of the various strategies, which have been utilized for miRNA delivery with a specific focus on the preclinical evaluation of promising RNA nanoparticles for glioblastoma (GBM) targeted therapy.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age. It is characterized by an increase in the biosynthesis of androgens, anovulation, and infertility. PCOS has been reported as a polygenic entity in which multiple single nucleotide polymorphisms (SNPs) are associated with the clinical features of the pathology. Herein, we describe the common polymorphic variants in genes related to PCOS, their role in its pathogenesis, and etiology. Whole-genome association studies have been focused on women from Asian and European populations. The most common genes associated with PCOS are DENND1A, THADA, FSHR, and LHCGR. However, other genes have been associated with PCOS such as AMH, AMHR2, ADIPOQ, FTO, HNF1A, CYP19, YAP1, HMGA2, RAB5B, SUOX, INSR, and TOX3. Nevertheless, the relationship between the biological functions of these genes and the development of the pathology is unclear. Studies in each gene in different populations do not always comply with a general pattern, so researching these variants is essential for better understanding of this polygenic syndrome. Future population studies should be carried out to evaluate biological processes, incidence rates, allelic and genotypic frequencies, and genetic susceptibility factors that predispose PCOS.

There is a paucity of data on the prognostic value of programmed cell death protein 1 (PD-1) protein and gene expression in early breast cancer (BC) and the present study's aim was to comprehensively investigate it.

Sex hormone-binding globulin (SHBG) is a plasma glycoprotein that binds androgens and oestrogens, and regulates their bioavailability to target tissues. To date, several human SHBG gene polymorphisms have been identified. Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, and hyperandrogenism has been considered to be a hallmark of PCOS. Many studies have examined the association between SHBG gene polymorphisms and PCOS risk, but the results have been inconclusive or inconsistent. Therefore, the aim of this meta-analysis was to investigate whether SHBG gene polymorphisms are associated with risk of PCOS. Twelve studies were included, involving 4733 participants: 2271 patients with PCOS and 2462 control participants. The results revealed that SHBG polymorphism of eight or more (TAAAA)n pentanucleotide repeats (rs35785886) was associated with PCOS risk (odds ratio [OR] = 1.24, 95% confidence interval [CI] = 1.06, 1.44, Z = 2.77, P = 0.006) and low serum SHBG concentrations in women with PCOS (standardized mean difference = -0.83, 95% CI = -1.54, -0.12, Z = 2.30, P = 0.02). Other SHBG gene polymorphisms (rs6259, rs6257, rs727428 and rs1799941) were not significantly associated with either PCOS risk or serum SHBG concentrations. These findings suggest that the presence of a polymorphism of eight or more SHBG (TAAAA)n may be a predictive factor for the risk of PCOS.

This systematic review aims to (1) characterize strategies used to identify individuals at increased risk for hereditary breast and ovarian cancer syndrome and Lynch syndrome outside of oncology and clinical genetic settings, (2) describe the extent to which these strategies have extended the reach of genetic services to underserved target populations, and (3) summarize indicators of the potential scalability of these strategies.

Gallbladder cancer (GBC) is an aggressive malignancy of the biliary tract. It is asymptomatic in its early stages, and often, characterized by a poor prognosis and worse treatment response. Distribution of GBC shows both geographical as well as ethnic variations. Several studies have elucidated the differential gene expression profile between the normal gallbladder and GBCs, with varied but inconsistent results. Thus, a deep understanding of the expression profile of GBC might aid in the identification of potential biomarkers, which would further help in better disease management and appropriate therapy selection. This review summarizes studies on the transcriptomic profile of GBC with emphasis on studies pertaining to coding (mRNA) and noncoding (micro and long noncoding) RNA along with aberrant promoter methylation studies, ranging from a single gene to global gene to high throughput RNA sequencing approaches, published between 2000 to May, 2019. In addition, data mining of GBC from the available public functional genomics data repository at Gene Expression Omnibus has been done to rule out potentially important dysregulated genes in this malignancy. To the best of our knowledge, this is the first article to shed light on the RNA based gene regulatory network(s) along with bioinformatic analysis. Moreover, this review represents major research challenges and ambiguity, knowledge of which is a must for establishing molecular/ clinical biomarkers for early GBC diagnosis, management, and treatment protocols.

Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor occurring supra- and infra-tentorially in both young adults and children. PXA is a benign tumor with a favorable prognosis. It is not traditionally considered as a neurofibromatosis type 1 (NF-1)-associated lesion, and its prognosis remains largely unknown, on the contrary to non-NF-1 PXA tumors.

A growing number of studies have suggested that the Long intergenic noncoding RNA 00511 (LINC00511) is aberrantly expressed in multiple malignancies and is related to patient survival. Herein, we conducted a systematic review and meta-analysis to comprehensively evaluate the prognostic significance of LINC00511 in human malignancies.

Aim: The aim was to systematically investigate the miRNA biomarkers for early diagnosis of hepatocellular carcinoma (HCC). Materials & methods: A systematic review and meta-analysis of miRNA expression in HCC were performed. Results: A total of 4903 cases from 30 original studies were comprehensively analyzed. The sensitivity and specificity of miR-224 in discriminating early-stage HCC patients from benign lesion patients were 0.868 and 0.792, which were superior to α-fetoprotein. Combined miR-224 with α-fetoprotein, the sensitivity and specificity were increased to 0.882 and 0.808. Prognostic survival analysis showed low expression of miR-125b and high expression of miR-224 were associated with poor prognosis. Conclusion: miR-224 had a prominent diagnostic efficiency in early-stage HCC, with miR-224 and miR-125b being valuable in the prognostic diagnosis.

Rates of loco-regional recurrence and distant metastasis remain high among head and neck squamous cell carcinoma (HNSCC) patients, despite advancing cancer treatment modalities and therapeutic agents. One area that has generated considerable interest is the immune landscape of the tumour, heralding a wave of immune checkpoint inhibitors with notable efficacy in recurrent/metastatic HNSCC patients. However, HNSCC remains poorly served by biomarkers that can direct treatment in a personalised fashion to target the tumour heterogeneity seen between patients. Detection and analysis of circulating tumour cells (CTCs) in HNSCC has provided a previously unseen view of the metastasis forming cells that are potentially contributing to poor clinical outcomes. In particular, identifying CTC expression of phenotypic and druggable protein markers has allowed CTC sub-populations to be defined that hold prognostic value or are potential therapeutic targets themselves. The aim of this systematic review was to examine the role of CTC immune-marker expression as prognostic/therapeutic biomarkers in HNSCC by evaluating progress to date and discussing areas for future research. Our results highlight how few studies have been able to demonstrate prognostic significance of immune-marker expression in CTCs. As expected, the immune checkpoint PD-L1 was the most widely investigated marker. However, no studies evaluated CTC target immune marker expression in immunotherapy cohorts. Despite these findings, the data presented demonstrate promise that CTCs may be a source of future biomarkers for immunotherapy and will provide valuable information regarding the potential immune evasion of these metastasis forming cells.

Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967-2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients with both symptomatic and asymptomatic (carriers) genetic parkinsonisms. Pooled proportions were calculated with random-effects meta-analyses. Out of 9,967 eligible articles, 60 were included. Of the 28 genetic variants associated with parkinsonism, six were also associated with cancer. In cancer samples, SNCA was predominantly associated with gastrointestinal cancers, UCHL1 with breast cancer, and PRKN with head-and-neck cancers. In asymptomatic carriers, LRRK2 was predominantly associated with gastrointestinal and prostate cancers, PRKN with prostate and genitourinary tract cancers, GBA with sarcoma, and 22q11.2 deletion with leukemia. In symptomatic genetic parkinsonism, LRRK2 was associated with nonmelanoma skin cancers and breast cancers, and PRKN with head-and-neck cancers. Cancer was more often manifested in genetic parkinsonisms compared to asymptomatic carriers. These results suggest that intraindividual genetic contributions may modify the co-occurrence of cancer and neurodegeneration.

Bufalin is an anticancer drug extract from traditional Chinese medicine. Several articles about bufalin have been published. However, the literature on bufalin has not yet been systematically studied. This study aimed to identify the study status and knowledge structures of bufalin and to summarize the antitumor mechanism. Data were retrieved and downloaded from the PubMed database. The softwares of BICOMB, gCLUTO, Ucinet 6.0, and NetDraw2.084 were used to analyze these publications. The bufalin related genes were recognized and tagged by ABNER software. Then these BF-related genes were performed by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, and protein-protein interaction (PPI) network analysis. A total of 474 papers met the search criteria from 2000 to 2019. By biclustering clustering analysis, the 50 high-frequency main MeSH terms/subheadings were classified into 5 clusters. The clusters of drug therapy and the mechanism of bufalin were hotspot topics. A total of 50 genes were identified as BF-related genes. PPI network analysis showed that inducing apoptosis was the main effect of bufalin, and apoptosis-related gene Caspase 3 was the most reported by people. Bufalin could inhibit the proliferation, invasion, and metastasis of cancer cells through multiple signaling pathways, such as PI3K/AKT, Hedgehog, MAPK/JNK, Wnt/[Formula: see text]-catenin, TGF-[Formula: see text]/Smad, Integrin signaling pathway, and NF-KB signaling pathway via KEGG analysis. Through the quantitative analysis of bufalin literature, we revealed the research status and hot spots in this field and provided some guidance for further research.

The insulin-like growth factor bioregulation system is implicated in cancer biology. Herein, we aim to review the evidence on the expression of the insulin-like growth factor 1 and 2 (IGF1 and IGF2), their receptors (IGF-Rs) and IGF-binding proteins (IGFBPs) in thyroid tissue and their possible association with benign and malignant thyroid nodular diseases.

: Antibodies against programmed death-1 (PD-1), and its ligand, (PD-L1) have been approved recently for the treatment of small-cell lung cancer (SCLC). Although there are previous reports that addressed PD-L1 detection on tumour cells in SCLC, there is no comprehensive meta-analysis on the prevalence of PD-L1 expression in SCLC. We performed a systematic search of the PubMed, Cochrane Library and EMBASE databases to assess reports on the prevalence of PD-L1 expression and the association between PD-L1 expression and overall survival (OS). This meta-analysis included 27 studies enrolling a total of 2792 patients. The pooled estimate of PD-L1 expression was 26.0% (95% CI 17.0-37.0), (22.0% after removing outlying studies). The effect size was significantly heterogeneous (I2 = 97.4, 95% CI: 95.5-98.5, p < 0.0001).Positive PD-L1 expression was a favourable prognostic factor for SCLC but not statistically significant (HR = 0.86 (95% CI (0.49-1.50), p = 0.5880; I2 = 88.7%, p < 0.0001). Begg's funnel plots and Egger's tests indicated no publication bias across included studies (p > 0.05). Overall, there is heterogeneity in the prevalence of PD-L1 expression in SCLC tumour cells across studies. This is significantly moderated by factors such as immunohistochemistry (IHC) evaluation cut-off values, and assessment of PD-L1 staining patterns as membranous and/or cytoplasmic. There is the need for large size, prospective and multicentre studies with well-defined protocols and endpoints to advance the clinical value of PD-L1 expression in SCLC.

Rate-limiting enzyme 3b-hydroxysteroid dehydrogenase type 1 (3βHSD1) encoded by HSD3B1 catalyzes the transition of dehydroepiandrosterone (DHEA) to dihydrotestosterone (DHT). The HSD3B1 (1245C) variant renders 3bHSD1 of resistant to ubiquitination and degradation, leading to a large amount of protein accumulation in the cell. Multiple clinical studies have shown that this mutation was correlated with resistance to androgen-deprivation therapy in prostate cancer. However, the results were not consistent depending on different treatment strategy and in some researches, the number of observed cases was relatively small.

This meta-analysis aims to explore the diagnostic value and accuracy of circulating lncRNAs as biomarkers of digestive system tumors.

Pathogenic variants in the BRCA1 and BRCA2 genes increase the risk of breast and ovarian cancer. Individuals with identified pathogenic variants in the BRCA1 or BRCA2 gene can benefit from cancer risk-reducing strategies. In the recent years, there has been an increase in the demand of genetic services. In light of the ongoing COVID19 pandemic, alternatives to face-to-face consultations have had to be considered and adopted, including telemedicine. Informed consent is necessary for genetic testing. Studies have suggested that increased levels of cancer-specific distress may impair the patient's ability to retain information, therefore, providing informed consent. This systematic review and meta-analysis aimed to answer if telephone genetic counseling for BRCA1 and BRCA2 genetic testing is non-inferior to in-person genetic counseling for the outcomes of cancer-specific distress and genetic knowledge. Databases of Medline, Embase, PsycINFO, CINAHL, SciELO, Web of Science, CENTRAL, ProQuest Dissertation & Theses Database, Clinicaltrials.gov, EU clinical trials register were accessed to identify any published or unpublished relevant literature. Random-effects models were used for the meta-analysis. Four studies were included in the qualitative synthesis of the results. Three studies were included in the quantitative synthesis of the results. Telephone genetic counseling was non-inferior compared to in-person genetic counseling for the outcomes of cancer-specific distress and genetic knowledge. Sensitivity analysis corroborated the main results. Telephone genetic counseling for BRCA1/BRCA2 genetic testing may be an alternative model of delivering genetic services in front of the increased demand/or when required by social context. However, the paucity of the evidence prevents from drawing strong conclusions regarding the generalizability of these results. Further research is needed to strengthen the conclusions.

DNA methylation is a potential biomarker for early detection of breast cancer. However, robust evidence of a prospective relationship between DNA methylation patterns and breast cancer risk is still lacking. The objective of this study is to provide a systematic analysis of the findings of epigenome-wide DNA methylation studies on breast cancer risk, in light of their methodological strengths and weaknesses.

Secondary angiosarcoma (AS) most commonly follows breast cancer and includes postirradiation AS (PRAS) and lymphedema-associated AS. The frequent amplification of MYC (8q24.21) in secondary AS and the rising incidence of PRAS and atypical vascular lesions (AVLs) have prompted interest in the diagnostic and prognostic utility of MYC in AS.

The present study was conducted to evaluate the prevalence of the signaling pathways mutation rate in the Gastrointestinal (GI) tract cancers in a systematic review and meta-analysis study. The study was performed based on the PRISMA criteria. Random models by confidence interval (CI: 95%) were used to calculate the pooled estimate of prevalence via Metaprop command. The pooled prevalence indices of signal transduction pathway mutations in gastric cancer, liver cancer, colorectal cancer, and pancreatic cancer were 5% (95% CI: 3-8%), 12% (95% CI: 8-18%), 17% (95% CI: 14-20%), and 20% (95% CI: 5-41%), respectively. Also, the mutation rates for Wnt pathway and MAPK pathway were calculated to be 23% (95% CI, 14-33%) and 20% (95% CI, 17-24%), respectively. Moreover, the most popular genes were APC (in Wnt pathway), KRAS (in MAPK pathway) and PIK3CA (in PI3K pathway) in the colorectal cancer, pancreatic cancer, and gastric cancer while they were beta-catenin and CTNNB1 in liver cancer. The most altered pathway was Wnt pathway followed by the MAPK pathway. In addition, pancreatic cancer was found to be higher under the pressure of mutation compared with others based on pooled prevalence analysis. Finally, APC mutations in colorectal cancer, KRAS in gastric cancer, and pancreatic cancer were mostly associated gene alterations.