The effects of the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms on bladder cancer risk have been evaluated in some studies. However, the results were conflicting and ambiguous. Therefore, we aimed to perform a comprehensive meta-analysis to investigate the association of these polymorphisms with risk of bladder cancer from all eligible case-control studies. PubMed, Web of science, Scopus, SID, CNKI and SciELO databases were searched to identify all relevant studies published up to 1 January, 2021. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 20 case-control studies including 11 studies with 3463 cases and 3927 controls on MTHFR rs1801133 (677C>T) and 9 studies with 3177 cases and 3502 controls on rs180113 (1298A>C) polymorphism were selected. Pooled data revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not associated with risk bladder cancer in overall. Stratified analysis by ethnicity revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were associated with bladder cancer risk in Asians, but not in Caucasians. There was no publication bias. The current meta-analysis revealed that the MTHFR rs1801133 (677C>T) and rs180113 (1298A>C) polymorphisms were not risk factor for development of bladder cancer globally. However, large sample size, well-designed, and population-based studies should be performed to verify the association of the MTHFR polymorphisms with bladder cancer risk.

Clear cell renal cell carcinoma (ccRCC) is the most prevalent subtype of renal cell carcinoma, which is characterized by metabolic reprogramming. Cuproptosis, a novel form of cell death, is highly linked to mitochondrial metabolism and mediated by protein lipoylation. However, the clinical impacts of cuproptosis-related genes (CRGs) in ccRCC largely remain unclear. In the current study, we systematically evaluated the genetic alterations of cuproptosis-related genes in ccRCC. Our results revealed that CDKN2A, DLAT, DLD, FDX1, GLS, PDHA1 and PDHB exhibited differential expression between ccRCC and normal tissues (|log2(fold change)| > 2/3 and p < 0.05). Utilizing an iterative sure independence screening (SIS) method, we separately constructed the prognostic signature of CRGs for predicting the overall survival (OS) and progression-free survival (PFS) in ccRCC patients. The prognostic score of CRGs yielded an area under the curve (AUC) of 0.658 and 0.682 for the prediction of 5-year OS and PFS, respectively. In the Kaplan−Meier survival analysis of OS, a higher risk score of cuproptosis-related gene signature was significantly correlated with worse overall survival (HR = 2.72 (2.01−3.68), log-rank p = 1.76 × 10−7). Patients with a higher risk had a significantly shorter PFS (HR = 2.83 (2.08−3.85), log-rank p = 3.66 × 10−7). Two independent validation datasets (GSE40435 (N = 101), GSE53757 (N = 72)) were collected for meta-analysis, suggesting that CDKN2A (log2(fold change) = 1.46, 95%CI: 1.75−2.35) showed significantly higher expression in ccRCC tissues while DLAT (log2(fold change) = −0.54, 95%CI: −0.93−−0.15) and FDX1 (log2(fold change) = −1.01, 95%CI: −1.61−−0.42) were lowly expressed. The expression of CDKN2A and FDX1 in ccRCC was also significantly associated with immune infiltration levels and programmed cell death protein 1 (PD-1) expression (CDKN2A: r = 0.24, p = 2.14 × 10−8; FDX1: r = −0.17, p = 1.37 × 10−4). In conclusion, the cuproptosis-related gene signature could serve as a potential prognostic predictor for ccRCC patients and may offer novel insights into the cancer treatment.

EGFR exon 20 insertion mutation-positive non-small cell lung cancer (NSCLC) is rare, has a poor prognosis, and outcomes are not fully established. We describe and evaluate outcomes from real-world and clinical evidence in these patients.

MicroRNAs (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional regulation of genes. Deregulated expression of miRNAs is involved in different pathogenic mechanisms, particularly colorectal cancer (CRC) carcinogenesis. Due to their stability and accessibility, circulating miRNAs represent a new family of biomarkers with great potential. Therefore, certain miRNAs can be used as diagnostic biomarkers in CRC.

Accumulating evidence demonstrated that FOXD1 dysregulation was correlated with a broad spectrum of malignancies. However, litter is known about the role of FOXD1 in the progression of lung squamous cell carcinoma (LUSC). We conducted the comprehensive bioinformatics analysis to investigate FOXD1 expression in LUSC from TCGA and GEO datasets, and validated the FOXD1 expression pattern in clinical samples using immunohistochemistry method. ESTIMATE and CIBERSORT algorithms were performed to assess the relationship of FOXD1 and tumor microenvironment and immune cell infiltration. Our study showed that FOXD1 expression was significantly upregulated in LUSC tissues in TCGA dataset, validated by GEO datasets and clinical samples. In TCGA dataset, Kaplan-Meier curves showed that high FOXD1 expression was significantly correlated with favorable prognosis in LUSC patients. Moreover, FOXD1 expression has an impact on immune score and the proportions of immune cell infiltration subgroups. Finally, we predicted FOXD1 may be involved in many immune-related biological functions and cancer-related signaling pathways. Taken together, FOXD1 was upregulated in LUSC tissues, and FOXD1 expression could be a potential prognostic marker. FOXD1 might be associated with tumor microenvironment and perhaps a potential target in the tumor immunotherapy.

Circular RNAs (circRNAs) have been found to have potential biological applications against tumors in humans. This study aimed to evaluate the diagnostic, prognostic, and clinicopathological value of circRNAs in head and neck squamous cell carcinoma (HNSCC).

Hepatitis B virus (HBV) infection has been reported to be associated with gastric cancer (GC). Nonetheless, no study has revealed the role of HBV infection in the survival of patients with GC, and the mutation profiles of HBV-infected patients with GC have never been documented. Here, we performed an updated meta-analysis and found a significantly increased risk of GC in HBV-infected individuals (sOR, 1.29; 95% CI, 1.22-1.37). Furthermore, we observed that in the Anhui area, the rate of serum HBsAg positivity (OR, 1.62; 95% CI, 1.03-2.55) was significantly higher in GC patients than in controls. Moreover, our results showed that HBV-positive patients had significantly worse disease-free survival (HR, 1.98; 95% CI, 1.39-2.82) and overall survival (HR, 1.84; 95% CI, 1.19-2.85) than HBV-negative patients. The results of Cox proportional hazards regression proved that HBV infection was an independent adverse prognostic factor in GC. Furthermore, by performing targeted-NGS, we found unique mutation profiles in HBV-infected GC samples, including five frequently mutated protein-coding genes (KMT2B, KMT2D, SOX1, FGF12, and TUBB2B). Expression and survival analyses of these genes identified three novel candidate genes that may have potential roles in GC development. Gene Ontology enrichment analysis showed that the recurrent mutations in HBV-positive GC samples were related to cell proliferation, cell migration, and transcription. Taking together, our study proved that HBV infection is an independent prognostic factor in GC patients. The unique mutation profiles of HBV-infected patients with GC open a new research direction toward the underling mechanism between HBV infection and GC.

Gastric cancer (GC) has been identified as one of the most common malignancies. It was found that microRNAs can be used as potential biomarkers for GC diagnosis. The aim of this study was to estimate the diagnostic value of 4 potential microRNAs in GC.

The methionine synthase reductase (MTRR) gene encodes the MTRR enzyme involved in the metabolic pathway of homocysteine. Several studies investigated the effect of the MTRR rs1532268 gene polymorphism on the risk of gastric cancer (GC), but the results have been inconsistent.

Both interleukin (IL)-4 and IL-17 polymorphisms may be involved in the pathogenesis and progression of colorectal cancer (CRC). Herein, we designed a meta-analysis to assess the associations between IL-4, IL-4R, IL-17A, and IL-17F polymorphisms and CRC risk. Scopus, Web of Science, Cochrane Library, and PubMed databases were searched to retrieve articles published until October 21, 2021. We used crude odds ratio (OR) and 95% confidence interval assessing the association of the polymorphisms and CRC risk in 5 genetic models. Trial sequential analysis for the primary analyses was used to control random errors. Twenty-three studies (8: IL-4 rs2243250, 4: IL-4R rs1801275, 5: IL-17A rs2275913, and 6: IL-17F rs763780) were involved in the meta-analysis. The pooled OR (P-value) for the association between IL-4 rs2243250 polymorphism and the CRC risk was 1.11 (0.08), 1.27 (0.12), 1.07 (0.37), 1.09 (0.17), and 1.22 (0.12), for IL-4R rs1801275 polymorphism was 0.71 (0.18), 1.05 (0.76), 0.86 (0.37), 0.87 (0.41), and 0.69 (0.39), for IL-17A rs2275913 polymorphism was 1.83 (0.0003), 1.73 (0.06), 1.47 (<0.001), 1.61 (0.001), and 1.42 (0.15), and for IL-17F rs763780 polymorphism was 1.07 (0.48), 5.33 (0.02), 1.08 (0.49), 1.08 (0.47), and 8.42 (0.002) in allelic, homozygous, heterozygous, recessive, and dominant models, respectively. The G allele and GA genotype of IL-17A rs2275913 polymorphism and the CC genotype of IL-17F rs763780 polymorphism had an elevated risk in CRC cases. The ethnicity and genotyping method, sample size, control, and publication year were effective factors on the pooled results.

Mutational signatures are somatic mutation patterns enriching operational mutational processes, which can provide abundant information about the mechanism of cancer. However, understanding of the pathogenic biological processes is still limited, such as the association between mutational signatures and genes.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with high recurrence, metastasis, and poor treatment outcome. Prognostic survival biomarkers can be a valid tool for assessing a patient's life expectancy and directing therapy toward specific targets. Recent studies have reported microRNA (miR) might play a critical role in regulating different types of cancer. The main miR used as a diagnostic and prognostic biomarker and reported in the scientific literature for HNSCC is miR-21. Other miRs have been investigated to a lesser extent (miR-99a, miR-99b, miR-100, miR-143, miR-155, miR-7, miR-424, miR-183), but among these, the one that has attracted major interest is the miR-31.

BRCA1/2 mutations and homologous recombination deficiency (HRD) predispose to increased sensitivity to poly(ADP-ribose)polymerase (PARP) inhibitor treatment. Our aim was to evaluate the PARP inhibitors effect on progression free survival (PFS) in a subpopulation with homologous recombination proficient status (HRD-BRCA-). A systematic literature search was performed for all studies reporting on the effect of PARP inhibitors regarding PFS in the HRD-BRCA- subpopulation, in patients with epithelial ovarian, tubal or primary peritoneal cancers (EOC). Five studies were included, enrolling a population of 3413 patients, with 1070 of them being HRD-BRCA-. PARP inhibitors were effective in the treatment of EOC, regardless of HRD and BRCA status or line of therapy. The estimated pooled effect hazard ratio (HR), assessing PFS for PARP inhibitors compared with control, was 0.76 (95% CI: 0.65-0.88, I2 = 46%) in the HRD-BRCA- subpopulation. Comparing both subpopulations with HRD positive status (HRD+ BRCA+, HRD+ BRCA-) versus the HRD-BRCA-subpopulation, we have found statistically significant differences in the effect on PFS (P < 0.05 for every interaction test) favouring HRD positive subpopulations (HRD+ BRCA+, HRD+ BRCA-). In the HRD-BRCA- subpopulation of patients, PARP inhibitors used as the second- or later-line of therapy showed more pronounced effect then when given as first line treatment (P = 0.04). Treatment of EOC with PARP inhibitors showed a significant effect regarding PFS in the HRD-BRCA- subpopulation, although a much higher benefit was evident for patients with HRD+ status (HRD+ BRCA+ and HRD+ BRCA-). In the HRD- subpopulation second line PARP inhibitor treatment showed greater benefit compared to first line PARP inhibitor treatment.

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10-7 , of which 41 (EA) and 16 (AA) were also associated with CVD death, and 15 (EA) and 9 (AA) with cancer death. We built DNAm-based prediction models for all-cause mortality that predicted mortality risk after adjusting for clinical risk factors. The mortality prediction model trained by integrating DNAm with clinical risk factors showed an improvement in prediction of cancer death with 5% increase in the C-index in a replication cohort, compared with the model including clinical risk factors alone. Mendelian randomization identified 15 putatively causal CpGs in relation to longevity, CVD, or cancer risk. For example, cg06885782 (in KCNQ4) was positively associated with risk for prostate cancer (Beta = 1.2, PMR  = 4.1 × 10-4 ) and negatively associated with longevity (Beta = -1.9, PMR  = 0.02). Pathway analysis revealed that genes associated with mortality-related CpGs are enriched for immune- and cancer-related pathways. We identified replicable DNAm signatures of mortality and demonstrated the potential utility of CpGs as informative biomarkers for prediction of mortality risk.

Neurofibromatosis Type 1 (NF1) is a common genetic disorder frequently associated with cognitive deficits. Despite cognitive deficits being a key feature of NF1, the profile of such impairments in NF1 has been shown to be heterogeneous. Thus, we sought to quantitatively synthesize the extant literature on cognitive functioning in NF1. A random-effects meta-analysis of cross-sectional studies was carried out comparing cognitive functioning of patients with NF1 to typically developing or unaffected sibling comparison subjects of all ages. Analyses included 50 articles (Total NNF1 = 1,522; MAge = 15.70 years, range = 0.52-69.60), yielding 460 effect sizes. Overall moderate deficits were observed [g = -0.64, 95% CI = (-0.69, -0.60)] wherein impairments differed at the level of cognitive domain. Deficits ranged from large [general intelligence: g = -0.95, 95% CI = (-1.12, -0.79)] to small [emotion: g = -0.37, 95% CI = (-0.63, -0.11)]. Moderation analyses revealed nonsignificant contributions of age, sex, educational attainment, and parental level of education to outcomes. These results illustrate that cognitive impairments are diffuse and salient across the lifespan in NF1. Taken together, these results further demonstrate efforts should be made to evaluate and address cognitive morbidity in patients with NF1 in conjunction with existing best practices.

By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants.

Circulating tumor DNA (ctDNA) has emerged as a promising noninvasive biomarker to capture tumor genetics in patients with brain tumors. Research into its clinical utility, however, has not been standardized because the sensitivity and specificity of ctDNA remain undefined.

Whether TERT promoter mutation is related to more aggressive clinicopathologic features and worse outcomes in papillary thyroid carcinoma patients (PTCs) is still variable and controversial. Our intention was to investigate the risk or prognostic factors that may additionally predict the TERT promoter mutation doable of these lesions and new prevention techniques in PTCs. A total of 2,539 PTC patients with 11.50% TERT mutation have been analyzed using Revman 5.3 software in this study. The PubMed and Embase databases were systematically searched for works published until November 9, 2021. The following variables had been associated with an extended chance of TERT promoter mutation in PTC patients: age < 45 years (MD = 10.93, 95%CI = 7.25-14.61); gender = male (pooled OR = 1.63, 95%CI = 1.17-2.28); tumor size > 1 cm (MD = 0.56, 95%CI = 0.34-0.77); lymph node metastasis (pooled OR = 1.29, 95%CI = 0.93-1.79); vascular invasion (pooled OR = 1.78, 95%CI = 0.83-3.84); extrathyroidal extension (pooled OR = 2.00, 95%CI = 1.32-3.02); distant metastasis (pooled OR = 1.46, 95%CI = 1.04-2.04); advanced TNM stage (pooled OR = 3.19, 95%CI = 2.28-4.45). In addition, multifocality (pooled OR = 0.67, 95%CI = 0.14-3.24) had no affiliation with TERT promoter mutation in PTC patients. Our finding showed that age < 45 years, male, tumor size > 1 cm, lymph node metastasis, vascular invasion, and superior/advanced TNM stage were dangerous elements for TERT promoter mutation of worse effect in PTCs while that multifocality was once negatively correlated. TERT promoter mutation is drastically associated with recurrence and PTC-related mortality.

Background and aim: Increasing evidence has revealed the valuable diagnostic and prognostic applications of dysregulated microRNAs (miRNAs) in hepatoblastoma (HB), the most common hepatic malignancy during childhood. However, these results are inconsistent and remain to be elucidated. In the present study, we aimed to systematically compile up-to-date information regarding the clinical value of miRNAs in HB. Methods: Articles concerning the diagnostic and prognostic value of single miRNAs for HB were searched from databases. The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and hazard ratios (HRs) were separately pooled to explore the diagnostic and prognostic performance of miRNA. Subgroup and meta-regression analyses were further carried out only in the event of heterogeneity. Results: In all, 20 studies, involving 264 HB patients and 206 healthy individuals, met the inclusion criteria in the 6 included literature articles. For the diagnostic analysis of miRNAs in HB, the pooled SEN and SPE were 0.76 (95% CI: 0.72-0.80) and 0.75 (95% CI: 0.70-0.80), respectively. Moreover, the pooled PLR was 2.79 (95% CI: 2.12-3.66), NLR was 0.34 (95% CI: 0.26-0.45), DOR was 10.24 (95% CI: 6.55-16.00), and AUC was 0.83, indicating that miRNAs had moderate diagnostic value in HB. For the prognostic analysis of miRNAs in HB, the abnormal expressions of miR-21, miR-34a, miR-34b, miR-34c, miR-492, miR-193, miR-222, and miR-224 in patients were confirmed to be associated with a worse prognosis. The pooled HR was 1.74 (95% CI: 1.20-2.29) for overall survival and 1.74 (95% CI: 1.31-2.18) for event-free survival, suggesting its potential as a prognostic indicator for HB. Conclusion: To the best of our knowledge, this is the first comprehensive systematic review and meta-analysis that examines the diagnostic and prognostic role of dysregulated miRNAs in HB patients. The combined meta-analysis results supported the previous individual finds that miRNAs might provide a new, noninvasive method for the diagnostic and prognostic analyses of HB.

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are the current standard of care for advanced or metastatic non-small cell lung cancer (NSCLC) patients harboring EGFR activating mutations. However, the optimal strategy for elderly NSCLC patients is still under debate. This study was designed to explore the optimal first-line regimens by comparing diverse strategies for elderly and non-elderly EGFR-mutated NSCLC patients.