The incidence of gastroesophageal reflux disease (GERD) has been shown to be elevated in individuals with epilepsy. Traditional observational studies have led to a limited understanding of the effects of GERD and BE on epilepsy due to the interference of reverse causation and potential confounders.

E2F1 has been confirmed to be highly expressed in a variety of cancers. To better understand the prognostic value of E2F1 in cancer patients, this study was conducted to comprehensively evaluate the prognostic value of E2F1 in cancer according to published data.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

Many studies have reported that microRNA-221 (miR-221) is abnormally expressed in various cancers, and there has not been a study to systematically analyze the association between miR-221 and chemoresistance in different cancers.

To estimate the burden of alcohol-attributable cancer in East Asian populations accounting for aldehyde dehydrogenase-2 (ALDH2) genotype-specific cancer risk and alcohol exposure.

Prostate-specific antigen (PSA) screening for prostate cancer remains controversial because it increases overdiagnosis and overtreatment of clinically insignificant tumors. Accounting for genetic determinants of constitutive, non-cancer-related PSA variation has potential to improve screening utility. In this study, we discovered 128 genome-wide significant associations (P < 5 × 10-8) in a multi-ancestry meta-analysis of 95,768 men and developed a PSA polygenic score (PGSPSA) that explains 9.61% of constitutive PSA variation. We found that, in men of European ancestry, using PGS-adjusted PSA would avoid up to 31% of negative prostate biopsies but also result in 12% fewer biopsies in patients with prostate cancer, mostly with Gleason score <7 tumors. Genetically adjusted PSA was more predictive of aggressive prostate cancer (odds ratio (OR) = 3.44, P = 6.2 × 10-14, area under the curve (AUC) = 0.755) than unadjusted PSA (OR = 3.31, P = 1.1 × 10-12, AUC = 0.738) in 106 cases and 23,667 controls. Compared to a prostate cancer PGS alone (AUC = 0.712), including genetically adjusted PSA improved detection of aggressive disease (AUC = 0.786, P = 7.2 × 10-4). Our findings highlight the potential utility of incorporating PGS for personalized biomarkers in prostate cancer screening.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) revolutionized the therapeutic landscape of non-small-cell lung cancer (NSCLC). However, despite significant survival improvement, the emergence of resistance mechanisms represents a common event. In this meta-analysis, we compared the efficacy and safety of third-generation EGFR-TKIs, the current standard of care, to first-generation EGFR-TKIs with antiangiogenic drugs for the first-line treatment of NSCLC harboring EGFR mutations.

Presence of circulating tumor DNA (ctDNA) is prognostic in solid tumors treated with curative intent. Studies have evaluated ctDNA at specific "landmark" or multiple "surveillance" time points. However, variable results have led to uncertainty about its clinical validity.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs; p < 1 × 10-9) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci, CD46, IKBKE, PARK2, ULK4, ATG5, and CDKN2A associated with MM risk (p = 4.47 × 10-4-5.79 × 10-14). Mechanistically, we found that the ULK4rs6599175 SNP correlated with circulating concentrations of vitamin D3 (p = 4.0 × 10-4), whereas the IKBKErs17433804 SNP correlated with the number of transitional CD24+CD38+ B cells (p = 4.8 × 10-4) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (p = 3.6 × 10-4). We also found that the CD46rs1142469 SNP correlated with numbers of CD19+ B cells, CD19+CD3- B cells, CD5+IgD- cells, IgM- cells, IgD-IgM- cells, and CD4-CD8- PBMCs (p = 4.9 × 10-4-8.6 × 10-4) and circulating concentrations of interleukin (IL)-20 (p = 0.00082). Finally, we observed that the CDKN2Ars2811710 SNP correlated with levels of CD4+EMCD45RO+CD27- cells (p = 9.3 × 10-4). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3-, MCP-2-, and IL20-dependent pathways.

In this study, we conducted a systematic review and meta-analysis to summarize and evaluate the global research potential of different circulating miRNAs as an early diagnostic biomarker for OC. A systematic literature search for relevant studies was conducted in June 2020 and followed up in November 2021. The search was conducted in English databases (PubMed, ScienceDirect). The primary search resulted in a total of 1887 articles, which were screened according to the prior established inclusion and exclusion criteria. We identified 44 relevant studies, of which 22 were eligible for the quantitative meta-analysis. Statistical analysis was performed using the Meta-package in Rstudio. Standardized mean differences (SMD) of relative levels between control subjects and OC patients were used to evaluate the differential expression. All studies were quality evaluated using a Newcastle-Ottawa Scale. Based on the meta-analysis, nine miRNAs were identified as dysregulated in OC patients compared to controls. Nine were upregulated in OC patients compared to controls (miR-21, -125, -141, -145, -205, -328, -200a, -200b, -200c). Furthermore, miR-26, -93, -106 and -200a were analyzed, but did not present an overall significant difference between OC patients and controls. These observations should be considered when performing future studies of circulating miRNAs in relation to OC: sufficient size of clinical cohorts, development of consensus guidelines for circulating miRNA measurements, and coverage of previously reported miRNAs.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

MicroRNA-27a (miR-27a) has been reported to be abnormally expressed in patients with cancer, and it could play potential roles as a diagnostic and prognostic biomarker of cancers. However, the diagnostic and prognostic role remains unclear. Hence, this meta-analysis, based on published data, was conducted to assess the utility of miR-27a as a diagnostic and prognostic marker in various cancers. To identify eligible studies, databases: Web of Science, PubMed, and CNKI were searched, with 868 literatures obtained, 16 of which were included in the Meta-analysis. The pooled results of studies conducted with serum/plasma showed that miR-27a was a valuable diagnostic biomarker in cancers (area under curve (AUC)= 0.91, sensitivity (SEN)= 0.84, specificity (SPE)= 0.85), with the diagnostic value slightly reduced in tumor tissue samples (AUC=0.83, SEN=0.78, SPE: 0.74). Additionally, the pooled results revealed that high expression of miR-27a predicted poor prognosis of cancer in serum/plasma (hazard ratio (HR) = 0.63, PHeterogeneity = 0.278, I2= 21.50%) but not in tumor tissue (HR = 0.98, PHeterogeneity =0.577, I2= 0.0). In brief, our results suggested that miR-27a in serum/plasma or tumor tissue could act as a diagnostic biomarker, and that miR-27a in serum/plasma could predict cancer patients' survival.

Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts.

To provide accurate figures of the frequency of specific clinical features in ovarian cancer (OC) associated with germline BRCA1/2 pathogenic variants and to define their relevance in predicting the presence of a germline pathogenic variant in these genes.

To systematically appraise and synthesize available epidemiologic evidence on the associations of environmental and genetic factors with the risk of sporadic early-onset colorectal cancer (EOCRC) and early-onset advanced colorectal adenoma (EOCRA).

PARP inhibitors (PARPi) have a well-established role in platinum-sensitive ovarian cancer (PSOC), in BRCA mutant (BRCAm), and homologous recombination deficiency (HRD) population. However, their role in wild type and homologous recombination proficient population is still not clear.

Current observational studies suggest that there may be a causal relationship between systemic lupus erythematosus (SLE) and prostate cancer (PC). However, there is contradictory evidence. This study aimed to investigate and clarify the association between SLE and PC.

The WHO 2021 classification defines IDH wild type (IDHw) histologically lower-grade glioma (hLGG) as molecular glioblastoma (mGBM) if TERT promoter mutation (pTERTm), EGFR amplification or chromosome seven gain and ten loss aberrations are indicated. We systematically reviewed articles of IDHw hLGGs studies (49 studies, N = 3748) and meta-analyzed mGBM prevalence and overall survival (OS) according to the PRISMA statement. mGBM rates in IDHw hLGG were significantly lower in Asian regions (43.7%, 95% confidence interval [CI: 35.8-52.0]) when compared to non-Asian regions (65.0%, [CI: 52.9-75.4]) (P = 0.005) and were significantly lower in fresh-frozen specimen when compared to formalin-fixed paraffin-embedded samples (P = 0.015). IDHw hLGGs without pTERTm rarely expressed other molecular markers in Asian studies when compared to non-Asian studies. Patients with mGBM had significantly longer OS times when compared to histological GBM (hGBM) (pooled hazard ratio (pHR) 0.824, [CI: 0.694-0.98], P = 0.03)). In patients with mGBM, histological grade was a significant prognostic factor (pHR 1.633, [CI: 1.09-2.447], P = 0.018), as was age (P = 0.001) and surgical extent (P = 0.018). Although bias risk across studies was moderate, mGBM with grade II histology showed better OS rates when compared to hGBM.

We performed an umbrella meta-analysis to explore the factors that influence the efficacy of immune checkpoint inhibitor (ICI) therapy.

Gastrointestinal (GI) tumors have increasing incidence worldwide with their underlying mechanisms still not being fully understood. The use of tumor-educated platelets (TEPs) in liquid biopsy is a newly-emerged blood-based cancer diagnostic method. Herein, we aimed to investigate the genomic changes of TEPs in GI tumor development and their potential functions using network-based meta-analysis combined with bioinformatic methods. We used a total of three eligible RNA-seq datasets, which were integrated using multiple meta-analysis methods on the NetworkAnalyst website, and identified 775 DEGs (differentially expressed genes; 51 up-regulated and 724 down-regulated genes) in GI tumor relative to healthy control (HC) samples. These TEP DEGs were mostly enriched in bone marrow-derived cell types and associated with gene ontology (GO) of "carcinoma" and could affect pathways of "Integrated Cancer Pathway" and "Generic transcription pathway" respectively for highly and lowly expressed DEGs. Combined network-based meta-analysis and protein-protein interaction (PPI) analysis identified cyclin dependent kinase 1 (CDK1) and heat shock protein family A (Hsp70) member 5 (HSPA5) to be the hub genes with the highest degree centrality (DC), being up-regulated and down-regulated in TEPs, respectively. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that the hub genes were primarily related to cell cycle and division, nucleobase-containing compound and carbohydrate transport, and endoplasmic reticulum unfolded protein response. Additionally, the nomogram model suggested that the two-gene signature owns extraordinary predictive power for GI tumor diagnosis. Further, the two-gene signature was demonstrated to have potential value for metastatic GI tumor diagnosis. The expression levels of CDK1 and HSPA5 in clinical platelet samples were verified to be consistent with the results from bioinformatic analysis. This study identified a two-gene signature encompassing CDK1 and HSPA5 that can be used as a biomarker for GI tumor diagnosis and maybe even cancer-associated thrombosis (CAT)-related prognosis.