The purpose of the study was to evaluate whether KRAS mutation could be an independent prognostic biomarker in patients undergoing pulmonary metastasectomy (PM) for colorectal cancer (CRC).

Molecular and functional profiling of cancer cell lines is subject to laboratory-specific experimental practices and data analysis protocols. The current challenge therefore is how to make an integrated use of the omics profiles of cancer cell lines for reliable biological discoveries. Here, we carried out a systematic analysis of nine types of data modalities using meta-analysis of 53 omics studies across 12 research laboratories for 2,018 cell lines. To account for a relatively low consistency observed for certain data modalities, we developed a robust data integration approach that identifies reproducible signals shared among multiple data modalities and studies. We demonstrated the power of the integrative analyses by identifying a novel driver gene, ECHDC1, with tumor suppressive role validated both in breast cancer cells and patient tumors. The multi-modal meta-analysis approach also identified synthetic lethal partners of cancer drivers, including a co-dependency of PTEN deficient endometrial cancer cells on RNA helicases.

Epidemiological studies have demonstrated a positive association between chronic lymphocytic leukaemia (CLL) and non-melanoma skin cancer (NMSC). We hypothesized that shared genetic risk factors between CLL and NMSC could contribute to the association observed between these diseases.

We comprehensively searched electronic databases, namely, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WanFang databases up to December 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the association between PRDX1 protein expression and the survival of patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to estimate the correlation between PRDX1 protein expression and clinicopathologic characteristics in the patients.

The lncRNA taurine upregulated gene 1 (TUG1) is a recently identified potential biomarker in cancer. However, its prognostic role in various cancers is inconsistent among published data. We conducted this meta-analysis to comprehensively confirm the prognostic effect of TUG1 in malignant tumors.

The polymorphism rs2853669 in the telomerase reverse transcriptase gene (TERT) promoter region is widely investigated for the risk of different cancers. However, previous results remained inconclusive. Thus, we performed this updated meta-analysis to comprehensively evaluate the association between rs2853669 and the susceptibility of human cancer. A systematic literature search via PubMed, EMBASE, Cochrane Library, and Web of Science databases was conducted that produced a total of 19 eligible studies containing 23,085 subjects. The relationship was calculated with the odds ratio (OR) and 95% confidence intervals (CIs). Statistical analyses were performed using the RevMan 5.4 software. The analysis indicated that rs2853669 is associated with an enhanced risk of overall cancer risk. From subgroup analysis, a significantly increased association in five genetic models (p < 0.05) was found among Asians, but no association was observed in Caucasians. Although we did not find any significant correlation between rs2853669 and breast cancer, an increased and statistically significant association was found for both lung cancer and acute myeloid leukemia. We did not find any association in other cancer types during stratified analysis. Our meta-analysis suggests that rs2853669 polymorphism in TERT gene is associated with an increased risk of overall cancer susceptibility, particularly in the Asian population. Moreover, rs2853669 is significantly associated with lung cancer and acute myeloid lymphoma. However, large-scale studies are needed to confirm our findings.

Epidemiological studies of adult glioma have identified genetic syndromes and 25 heritable risk loci that modify individual risk for glioma, as well increased risk in association with exposure to ionizing radiation and decreased risk in association with allergies. In this analysis, we assess whether there is a shared genome-wide genetic architecture between glioma and atopic/autoimmune diseases.

Cadherin-5 (CDH5) is aberrantly expressed in a variety of human cancers and plays an important role in angiogenesis. The present study provides further insight into the role of miR-27a-3p in the regulation of CDH5 expression in renal clear cell carcinoma (ccRCC).

The authors performed a meta-analysis to better quantify the benefit of maintenance poly(ADP-ribose) polymerase inhibitor (PARPi) therapy to inform practice in platinum-sensitive, recurrent, high-grade ovarian cancer for patient subsets with the following characteristics: germline BRCA mutation (gBRCAm), somatic BRCA mutation (sBRCAm), wild-type BRCA but homologous recombinant-deficient (HRD), homologous recombinant-proficient (HRP), and baseline clinical prognostic characteristics.

Previous genome-wide association studies (GWASs) have been largely focused on European (EUR) populations. However, polygenic risk scores (PRSs) derived from EUR have been shown to perform worse in non-EURs compared with EURs. In this study, we aim to improve PRS prediction in East Asians (EASs). We introduce a rescaled meta-analysis framework to combine both EUR (N = 122,175) and EAS (N = 30,801) GWAS summary statistics. To improve PRS prediction in EASs, we use a scaling factor to up-weight the EAS data, such that the resulting effect size estimates are more relevant to EASs. We then derive PRSs for EAS from the rescaled meta-analysis results of EAS and EUR data. Evaluated in an independent EAS validation data set, this approach increases the prediction liability-adjusted Nagelkerke's pseudo R2 by 40%, 41%, and 5%, respectively, compared with PRSs derived from an EAS GWAS only, EUR GWAS only, and conventional fixed-effects meta-analysis of EAS and EUR data. The PRS derived from the rescaled meta-analysis approach achieved an area under the receiver operating characteristic curve (AUC) of 0.6059, higher than AUC = 0.5782, 0.5809, 0.6008 for EAS, EUR, and conventional meta-analysis of EAS and EUR. We further compare PRSs constructed by single-nucleotide polymorphisms that have different linkage disequilibrium (LD) scores and minor allele frequencies (MAFs) between EUR and EAS, and observe that lower LD scores or MAF in EAS correspond to poorer PRS performance (AUC = 0.5677, 0.5530, respectively) than higher LD scores or MAF (AUC = 0.589, 0.5993, respectively). We finally build a PRS stratified by LD score differences in EUR and EAS using rescaled meta-analysis, and obtain an AUC of 0.6096, with improvement over other strategies investigated.

Recent research has suggested that long non-coding RNA (lncRNA) is involved in the tumorigenesis and development of breast cancer (BC). This meta-analysis aimed to identify the diagnostic role of lncRNAs in BC.

Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men, is less associated with smoking, but occurs at a younger age than sporadic tumours.

The main purpose of this study is to systematically evaluate the diagnostic value of long-chain non-coding RNA urothelial carcinoembryonic antigen 1 (lncRNA-UCA1) for bladder cancer, and to provide a scientific basis for the diagnosis of bladder cancer.

Chromodomain helicase DNA-binding protein 1-like (CHD1L) is an oncogene. It was cloned from 1q21 chromosome region of hepatocellular carcinoma in 1991. CHD1L is up-regulated in many kinds of cancers and is involved in the carcinogenesis and development of tumors. More and more studies have shown that over-expression of CHD1L is associated with poor prognosis of tumors. The purpose of this study was to evaluate the prognostic value of CHD1L in human solid tumors.

Latest clinical trials have proved the better overall survival (OS) for the use of immune checkpoint inhibitors verse chemotherapy in non-small cell lung cancer (NSCLC) patients. However, we still have no clear ideas of the factors which could affect the efficacy of immune checkpoint inhibitors. Cancer, essentially, is a disease related to genes mutation. Therefore, we conducted a systematic review and meta-analysis to compare efficacy of immune checkpoint inhibitors for NSCLC patients with different genes mutation.

Metastasis is the primary cause of lung cancer-related death. Nevertheless, the underlying molecular mechanisms and evolutionary patterns of lung cancer metastases are still elusive.

Helicobacter pylori is a gram-negative bacterium that colonizes the human gastric mucosa and can lead to gastric inflammation, ulcers, and stomach cancer. Due to the increase in H. pylori antimicrobial resistance new methods to identify the molecular mechanisms of H. pylori-induced pathology are urgently needed. Here we utilized a computational biology approach, harnessing genome-wide association and gene expression studies to identify genes and pathways determining disease development. We mined gene expression data related to H. pylori-infection and its complications from publicly available databases to identify four human datasets as discovery datasets and used two different multi-cohort analysis pipelines to define a H. pylori-induced gene signature. An initial Helicobacter-signature was curated using the MetaIntegrator pipeline and validated in cell line model datasets. With this approach we identified cell line models that best match gene regulation in human pathology. A second analysis pipeline through NetworkAnalyst was used to refine our initial signature. This approach defined a 55-gene signature that is stably deregulated in disease conditions. The 55-gene signature was validated in datasets from human gastric adenocarcinomas and could separate tumor from normal tissue. As only a small number of H. pylori patients develop cancer, this gene-signature must interact with other host and environmental factors to initiate tumorigenesis. We tested for possible interactions between our curated gene signature and host genomic background mutations and polymorphisms by integrating genome-wide association studies (GWAS) and known oncogenes. We analyzed public databases to identify genes harboring single nucleotide polymorphisms (SNPs) associated with gastric pathologies and driver genes in gastric cancers. Using this approach, we identified 37 genes from GWA studies and 61 oncogenes, which were used with our 55-gene signature to map gene-gene interaction networks. In conclusion, our analysis defines a unique gene signature driven by H. pylori-infection at early phases and that remains relevant through different stages of pathology up to gastric cancer, a stage where H. pylori itself is rarely detectable. Furthermore, this signature elucidates many factors of host gene and pathway regulation in infection and can be used as a target for drug repurposing and testing of infection models suitability to investigate human infection.

Aim: Long noncoding RNA (lncRNA) noncoding RNA activated by DNA damage (NORAD) is widely investigated in different tumors. Our meta-analysis intends to assess the prognostic and clinicopathological value of NORAD in cancers. Materials & methods: We searched PubMed, Web of Science, Embase and Chinese National Knowledge Infrastructure from inception to 1 August 2020. Results: The results showed that higher expression of NORAD had a significant association with worse overall survival. Additionally, correlations were detected between elevated level of NORAD and poor differentiation degree, positive lymph node metastasis and large tumor size in cancer patients. Conclusion: LncRNA NORAD can serve as a novel and promising biomarker for prognosis and clinicopathological characteristics in different cancers.

Human clear cell renal cell carcinoma (ccRCC) is the most common and frequently occurring histological subtype of RCC. Unlike other carcinomas, candidate predictive biomarkers for this type are in need to explore the molecular mechanism of ccRCC and identify candidate target genes for improving disease management. For this, we chose case-control-based studies from the Gene Expression Omnibus and subjected the gene expression microarray data to combined effect size meta-analysis for identifying shared genes signature. Further, we constructed a subnetwork of these gene signatures and evaluated topological parameters during the gene deletion analysis to get to the central hub genes, as they form the backbone of the network and its integrity. Parallelly, we carried out functional enrichment analysis using gene ontology and Elsevier disease pathway collection. We also performed microRNAs target gene analysis and constructed a regulatory network. We identified a total of 577 differentially expressed genes (DEGs), where 146 overexpressed and 431 underexpressed with a significant threshold of adjusted P values <0.05. Enrichment analysis of these DEGs' functions showed a relation to metabolic and cellular pathways like metabolic reprogramming in cancer, proteins with altered expression in cancer metabolic reprogramming, and glycolysis activation in cancer (Warburg effect). Our analysis revealed the potential role of PDHB and ATP5C1 in ccRCC by altering metabolic pathways and amyloid beta precursor protein (APP) role in altering cell-cycle growth for the tumour progression in ccRCC conditions. Identification of these candidate predictive genes paves the way for the development of biomarker-based methods for this carcinoma.

Mucosal melanoma is a rare subtype of melanoma. To date, there has been no comprehensive systematic collation and statistical analysis of the aberrations and aggregated frequency of driver events across multiple studies. Published studies using whole genome, whole exome, targeted gene panel, or individual gene sequencing were identified. Datasets from these studies were collated to summarize mutations, structural variants, and regions of copy-number alteration. Studies using next-generation sequencing were divided into the "main" cohort (n = 173; fresh-frozen samples), "validation" cohort (n = 48; formalin-fixed, paraffin-embedded samples) and a second "validation" cohort comprised 104 tumors sequenced using a targeted panel. Studies assessing mutations in BRAF, KIT, and NRAS were summarized to assess hotspot mutations. Statistical analysis of the main cohort variant data revealed KIT, NF1, BRAF, NRAS, SF3B1, and SPRED1 as significantly mutated genes. ATRX and SF3B1 mutations occurred more commonly in lower anatomy melanomas and CTNNB1 in the upper anatomy. NF1, PTEN, CDKN2A, SPRED1, ATM, CHEK2, and ARID1B were commonly affected by chromosomal copy loss, while TERT, KIT, BRAF, YAP1, CDK4, CCND1, GAB2, MDM2, SKP2, and MITF were commonly amplified. Further notable genomic alterations occurring at lower frequencies indicated commonality of signaling networks in tumorigenesis, including MAPK, PI3K, Notch, Wnt/β-catenin, cell cycle, DNA repair, and telomere maintenance pathways. This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted. IMPLICATIONS: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/19/6/991/F1.large.jpg.