Hypomethylating agents (HMAs) are now a major treatment option for myelodysplastic syndrome (MDS) and related neoplasms, but 50% of patients still do not respond and realize poor outcomes. Mutational predictors of treatment efficacy attract continuous attention. Whether TP53 mutations can be used as predictors of HMA effectiveness has caused heated debate. Therefore, we performed a meta-analysis to investigate the predictive value of TP53 mutations to outcomes of HMA therapy in patients with MDS and related neoplasms. We systematically searched PubMed, Embase, the Cochrane Library, and the WanFang databases (published deadline: September 12, 2019). The primary endpoints were overall response rate (ORR) and overall survival (OS). Odds ratio (OR), hazard ratio (HR), and 95% confidence intervals (CI) were pooled to estimate the association between TP53 mutations and the clinical efficacy of HMAs. Four hundred fifteen papers were found, and 22 papers were included in this meta-analysis (N = 2020 participants). The results showed that the presence of TP53 mutation predicted an increased overall response rate with HMA treatment in the subsets that restricted patients in de novo disease, MDS by WHO (World Health Organization) criteria, or NGS (next-generation sequence) group (P = 0.005, P = 0.003, P = 0.0005, respectively). However, TP53 mutations remained poor factors for OS (P < 0.00001). Collectively, in HMA therapy, TP53 mutations can predict better ORR when setting more refined subgroups, but TP53 mutations still strongly correlated with poor survival in hypomethylating therapy.

Background and objectives: The prognostic role of a disintegrin and metalloproteinase (ADAM) 17 has been widely assessed in gastric cancer. However, the results are inconsistent. We performed a meta-analysis to evaluate the prognostic significance of ADAM17 and its association with clinicopathological parameters. Methods: The databases of PubMed, Web of Science, and Embase were searched for relevant articles published up to April 2020. The reported hazard ratios (HRs) and odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were pooled to evaluate the strength of the association. Stata 12.1 was used to perform statistical analyses. Results: Seven studies, including 1757 patients, were screened for the meta-analysis. Compared with the high ADAM17 expression group, the pooled HR was higher in the low ADAM17 expression group (HR = 2.04, 95% CI 1.66-2.50; I2 = 18.1%; p = 0.299). High ADAM17 expression was also related to the tumor node metastasis (TNM) stages (OR = 4.09, 95% CI 1.85-9.04; I2 = 84.1%; p = 0.000), lymph node metastasis (OR = 3.08, 95% CI 1.13-8.36; I2 = 79.7%; p = 0.007), and ages (OR = 1.65, 95% CI 1.24-2.21; I2 = 0%; p = 0.692) of the gastric patients. Conclusions: This meta-analysis revealed that ADAM17 is a significant biomarker for poor prognosis in gastric cancer.

The use of next-generation sequencing technologies has enabled the rapid identification of non-synonymous somatic mutations in cancer cells. Neoantigens are mutated peptides derived from somatic mutations not present in normal tissues that may result in the presentation of tumour-specific peptides capable of eliciting antitumour T-cell responses. Personalised neoantigen-based cancer vaccines and adoptive T-cell therapies have been shown to prime host immunity against tumour cells and are under clinical trial development. However, the optimisation and standardisation of neoantigen identification, as well as its delivery as immunotherapy are needed to increase tumour-specific T-cell responses and, thus, the clinical efficacy of current cancer immunotherapies.

B-cell maturation antigen (BCMA) plays a critical role in regulating B-cell proliferation and survival. There is evidence for BCMA expression in various hematologic malignancies, suggesting that BCMA may play an important role as a biomarker or therapeutic target in these diseases. Given advances in understanding the role of BCMA in B-cell development and the promise of BCMA as a therapeutic target, a systematic review is needed to rigorously assess the evidence for BCMA expression and identify areas of consensus and future research. The objective of this review was to summarize the evidence on BCMA protein and mRNA expression across hematologic malignancies. Using a PubMed database search up to 28 August 2019, a systematic literature review of publications reporting BCMA expression in patients with hematologic malignancies was conducted. Data from published congress abstracts presented at the American Society of Clinical Oncology and the American Society of Hematology were also searched. Studies that assessed BCMA expression (protein or mRNA) in patients of any age with hematologic malignancies were included. A total of 21 studies met inclusion criteria and were included in the review. BCMA was expressed in several hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia, acute B-lymphoblastic leukemia, non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. BCMA was expressed at uniformly high levels across all 13 MM studies and at low to moderate levels in acute myeloid leukemia and acute lymphoblastic leukemia. These results suggest that BCMA is a relevant target in MM as well as in a subset of B-cell leukemia. BCMA expression in Hodgkin lymphoma and NHL varied across studies, and further research is needed to determine the utility of BCMA as an antibody target and biomarker in these diseases. Differences in sample type, timing of sample collection, and laboratory technique used may have affected the reporting of BCMA levels.

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools.Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies.Results: A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA -308 G > A and IL-10 - 1082A>G) and ZNF263 (TNFA -238 G > A) transcription factors binding.Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.

Mantle cell lymphoma (MCL) is an incurable rare subtype of non-Hodgkin lymphoma and is subject to relapse and therapeutic resistance. Molecular aberrations in MCL affect pathogenesis, prognosis, and therapeutic response. In this systematic review, we searched 3 databases and selected 32 articles that described mutations in MCL patients. We then conducted a meta-analysis using a Bayesian multiregression model to analyze patient-level data in 2127 MCL patients, including prevalence of mutations. In tumor or bone marrow samples taken at diagnosis or baseline, ATM was the most frequently mutated gene (43.5%) followed by TP53 (26.8%), CDKN2A (23.9%), and CCND1 (20.2%). Aberrations were also detected in IGH (38.4%) and MYC (20.8%), primarily through cytogenetic methods. Other common baseline mutations were NSD2 (15.0%), KMT2A (8.9%), S1PR1 (8.6%), and CARD11 (8.5%). Our data also show a change in mutational status from baseline samples to samples at disease progression and present mutations of interest in MCL that should be considered for future analysis. The genes with the highest mutational frequency difference (>5%) are TP53, ATM, KMT2A, MAP3K14, BTK, TRAF2, CHD2, TLR2, ARID2, RIMS2, NOTCH2, TET2, SPEN, NSD2, CARD11, CCND1, SP140, CDKN2A, and S1PR1. These findings provide a summary of the mutational landscape of MCL. The genes with the highest change in mutation frequency should be included in targeted next-generation sequencing panels for future studies. These findings also highlight the need for analysis of serial samples in MCL. Patient-level data of prevalent mutations in MCL provide additional evidence emphasizing molecular variability in advancing precision medicine initiatives in MCL.

Conflicting results have been reported about the prognostic value of programmed death ligand 1 (PD-L1) protein and gene expression in lung adenocarcinoma.

Early detection and preventive measures can reduce the risk of cancer among first degree relatives (FDRs) of cancer patients.Several studies investigated the effect of subjective norm in relation to FDRs' tendency to conduct preventive behaviors. Therefore, the purpose of this study was to systematically evaluate the effect of subjective norms on cancer patients' FDRs as well as their willingness for screening.

Glioma-associated oncogene homolog 1(GLI1) expression correlates with the clinical significance and prognosis of several cancers. However, the evaluation of the role GLI1 expression plays in pancreatic ductal adenocarcinoma (PDAC) clinicopathological features and outcomes still lacks.

Genome-wide association studies (GWAS) have identified multiple independent cancer susceptibility loci at chromosome 8q24. We aimed to evaluate the associations between variants in the 8q24 region and cancer susceptibility. A comprehensive research synopsis and meta-analysis was performed to evaluate associations between 28 variants in 8q24 and risk of 7 cancers using data from 103 eligible articles totaling 146,932 cancer cases and 219,724 controls. Results: 20 variants were significantly associated with risk of prostate cancer, colorectal cancer, thyroid cancer, breast cancer, bladder cancer, stomach cancer, and glioma, including 1 variant associated with prostate cancer, colorectal cancer, and thyroid cancer. Cumulative epidemiological evidence of an association was graded as strong for DG8S737 -8 allele, rs10090154, rs7000448 in prostate cancer, rs10808556 in colorectal cancer, rs55705857 in gliomas, rs9642880 in bladder cancer, moderate for rs16901979, rs1447295, rs6983267, rs7017300, rs7837688, rs1016343, rs620861, rs10086908 associated in prostate cancer, rs10505477, rs6983267 in colorectal cancer, rs6983267 in thyroid cancer, rs13281615 in breast cancer, and rs1447295 in stomach cancer, weak for rs6983561, rs13254738, rs7008482, rs4242384 in prostate cancer. Data from ENCODE suggested that these variants with strong evidence and other correlated variants might fall within putative functional regions. Our study provides summary evidence that common variants in the 8q24 are associated with risk of multiple cancers in this large-scale research synopsis and meta-analysis. Further studies are needed to explore the mechanisms underlying variants in the 8q24 involved in various human cancers.

Despite the demonstrated increased cardiovascular (CV) risk associated with metabolic-dysfunction-associated fatty liver disease (MAFLD), genetic variants predisposing to MAFLD were not constantly associated with CV events. Recently, rs641738C > T near membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) has been studied in MAFLD and CV outcomes. Therefore, we aimed to evaluate the association between rs641738C > T in the presence and severity of hepatic steatosis, fibrosis, biochemical markers and progression to hepatocellular carcinoma (HCC), in addition to CV outcomes in MAFLD.

Dishevelled (DVL) family members are crucial to Wnt-induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant cancers. However, the expression profiles and exact prognostic values of DVLs in hepatocellular carcinoma (HCC) have not been explored until now.

This systematic review examined educational training interventions for healthcare professionals (HCPs) discussing genetic testing and risk for hereditary breast cancer. There was a particular focus on the presence, and content, of communication elements within these packages.

While upper tract urothelial carcinoma (UTUC) share histological appearance with bladder cancer (BC), the former has differences in etiology and clinical phenotype consistent with characteristic molecular alterations.

Cancer immunotherapy is a rapidly growing field that is completely transforming oncology care. Mining this knowledge base for biomedically important information is becoming increasingly challenging, due to the expanding number of scientific publications, and the dynamic evolution of this subject with time. In this study, we have employed a literature-mining approach that was used to analyze the cancer immunotherapy-related publications listed in PubMed and quantify emerging trends. A total of 93,033 publications published in 5055 journals have been retrieved, and 141 meaningful topics have been identified, which were further classified into eight distinct categories. Statistical analysis indicates a mean annual increase in the number of published papers of approximately 8% in the last 20 years. The research topics that exhibited the highest trends included "immune checkpoint inhibitors," "tumor microenvironment," "HPV vaccination," "CAR T-cells," and "gene mutations/tumor profiling." The top identified cancer types included "lung," "colorectal," and "breast cancer," and a shift in popularity from hematological to solid tumors was observed. As regards clinical research, a transition from early phase clinical trials to randomized control trials was recorded, indicating that the field is entering a more advanced phase of development. Overall, this mining approach provided an unbiased analysis of the cancer immunotherapy literature in a time-conserving and scale-efficient manner.

Cancer is the single leading cause of human deaths worldwide. The highest incidence and mortality are recorded from Africa. The last two decades have witnessed extensive research which has led to emerging prognosis and new gene therapy technologies. Cancer therapy in Africa is derived with little input from African population data. While a number of cancer studies on African populations have suggested varied susceptible variant, no comprehensive review of these studies has been undertaken to assess their coverage across Africa.

Background: Archived formalin-fixed paraffin-embedded (FFPE) specimens from nonmalignant tissues derived from cancer patients are a vast and potentially valuable resource for high-quality genotyping analyses and could have a role in establishing inherited cancer risk. Methods: We systematically searched PubMed, Ovid MEDLINE, and Scopus databases for all articles that compared genotyping performance of DNA from nonmalignant FFPE tissue with blood DNA derived from cancer patients irrespective of tumor type. Two independent researchers screened the retrieved studies, removed duplicates, excluded irrelevant studies, and extracted genotyping data from the eligible studies. These studies included, but were not limited to, genotyping technique, reported call rate, and concordance. Results: Thirteen studies were reviewed, in which DNA from nonmalignant FFPE tissues derived from cancer patients was successfully purified and genotyped. All these studies used different approaches for genotyping of DNA from nonmalignant FFPE tissues to amplify single nucleotide polymorphisms (SNPs) and to estimate of loss of heterozygosity. The concordance between genotypes from nonmalignant FFPE tissues and blood derived from cancer patients was observed to be high, whereas the call rate of the tested SNPs was not reported in all included studies. Conclusion: This review illustrates that DNA from nonmalignant FFPE tissues derived from cancer patients can serve as an alternative and reliable source for assessment of germline DNA for various purposes, including assessment of cancer predisposition.

Members of the melanoma-associated antigen-A (MAGE-A) subfamily are overexpressed in many cancers and can drive cancer progression, metastasis, and therapeutic recurrence.

The objective of the study was to identify guidelines to assist systematic reviewers or clinical researchers in identifying sampling bias due to tumor heterogeneity (TH) in solid cancers assayed for somatic mutations. We also assessed current reporting standards to determine the impact of TH on sample bias.

To systematically summarise the available evidence on urinary bladder cancer (BC) mutation markers. Gene mutations are expected to provide novel biomarkers for urinary BC diagnosis. To date, evidence on urinary BC mutation markers has not proven sufficient to be adopted by clinical guidelines. In the present systematic review, diagnostic accuracy of urinary mutation analysis is separately assessed for primary BC diagnosis (BC detection) and for follow-up of BC patients (BC surveillance).