To summarize the associations between potential causal factors and colorectal cancer (CRC) risk based on existing Mendelian randomization studies.

This meta-analysis aimed to compare the efficacy of immunotherapy combined with chemotherapy versus chemotherapy alone as the first-line therapy for patients with programmed death ligand-1 (PD-L1)-negative and driver-gene-negative advanced nonsquamous non-small-cell lung cancer (NSCLC).

Patients whose tumours harbour epidermal growth factor receptor (EGFR), and anaplastic lymphoma kinase (ALK) driver mutations can benefit most from treatment with tyrosine kinase inhibitors (TKIs). Most trials with immune checkpoint inhibitors (ICIs) included few patients whose tumour had oncogenic driver alterations. We therefore performed a meta-analysis of studies reporting the activity of ICIs in oncogene addicted NSCLC. A comprehensive search of MEDLINE, The Cochrane Library and EMBASE was conducted to identify relevant studies published up to 31 January 2021. The primary outcomes were median overall survival (OS); the secondary endpoints were progression-free survival and overall response rate (PFS and ORR). Overall, 46 studies were screened and selected for final analysis. The pooled ORR was 14.5% (95% CI 9.6-21.2%). The median pooled PFS in EGFR/ALK mutated cases was 3.9 months (95% CI 3-5.2 months). Median pooled OS was 10.7 months (95% CI 9.2-12.5 months). All registration trials in second line did not show any benefit of immunotherapy for the subgroup of patients with EGFR-mutated or ALK-rearranged tumours. The unsatisfied benefit of immunotherapy in oncogene-addicted tumours has been debated and is mainly due to the lower mutation burden of these neoplasms. Our data do not support the use of immunotherapy in the setting of oncogene actionable tumours. More data are needed to confirm or reject the benefit of the combination of TKIs with ICIs.

The MTHFR gene polymorphisms are closely related to the chronic myeloid leukemia (CML). Case-control studies have associated the MTHFR polymorphisms and susceptibility to CML but the results were not conclusive.

Background: In non-small cell lung cancer (NSCLC) patients harboring MET mutations, MET-tyrosine kinase inhibitors (TKIs) have been proven to achieve a good response. However, the relative efficacy of different therapeutics in primary NSCLC patients with MET amplification and the treatment options for patients harboring acquired MET amplification after the failure of epidermal growth factor receptor (EGFR)-TKIs remain unclear. Methods: In total, 33 patients harboring primary MET amplification and 9 patients harboring acquired MET alterations identified by next-generation sequencing were enrolled. A retrospective analysis was conducted to compare the efficacy of different therapeutics. In addition, studies reporting various treatments for patients harboring MET alterations were included in the meta-analysis. Results: In our cohort of patients harboring primary MET amplification, crizotinib displayed better efficacy than immunotherapy and chemotherapy, as demonstrated both in first-line (P = .0378) and second-line treatment regimens (P = .0181). The disease control rates for crizotinib, immunotherapy, and chemotherapy were 81.8%, 72.7%, and 63.6%, respectively. In particular, the median progression-free survival (PFS) time after immunotherapy in patients harboring MET amplification and high programed death ligand 1 (PD-L1) expression (>50%) was only 77.5 days. The meta-analysis revealed that the median PFS times after crizotinib and immunotherapy were 4.57 and 2.94 months, respectively. In patients harboring acquired MET amplification, chemotherapy plus bevacizumab had superior efficacy (310.0 days vs 73.5 days, P = .0360) compared with MET-TKIs ± EGFR-TKIs. Conclusions: Immunotherapy showed a low response in patients harboring MET alterations, even those with concurrent high PD-L1 expression. MET-TKIs might be an optional treatment with worth-expecting efficacy. However, chemotherapy plus bevacizumab could benefit the subpopulation of patients harboring acquired MET amplification after the failure of EGFR-TKIs.

Hepatoid adenocarcinoma of the stomach (HAS) is a rare subtype of gastric cancer (GC) that histologically resembles hepatocellular carcinoma (HCC). Despite its low incidence, HAS had a poor 5-year survival rate. Currently, the linkages between clinicopathological and genomic features of HAS and its therapeutic targets remain largely unknown. Herein, we enrolled 90 HAS patients and 270 stage-matched non-HAS patients from our institution for comparing clinicopathological features. We found that HAS had worse overall survival and were more prone to develop liver metastasis than non-HAS in our cohort, which was validated via meta-analysis. By comparing whole-exome sequencing data of HAS (n=30), non-HAS (n=63), and HCC (n=355, The Cancer Genome Atlas), we identified a genomic landscape associated with unfavorable clinical features in HAS, which contained frequent somatic mutations and widespread copy number variations. Notably, signaling pathways regulating pluripotency of stem cells affected by frequent genomic alterations might contribute to liver metastasis and poor prognosis in HAS patients. Furthermore, HAS developed abundant multiclonal architecture associated with liver metastasis. Encouragingly, target analysis suggested that HAS patients might potentially benefit from anti-ERBB2 or anti-PD-1 therapy. Taken together, this study systematically demonstrated a high risk of liver metastasis and poor prognosis in HAS, provided a clinicogenomic landscape underlying these unfavorable clinical features, and identified potential therapeutic targets, laying the foundations for developing precise diagnosis and therapy in this rare but lethal disease.

To investigate the clinical benefits of combination therapy with immune checkpoint inhibitors (ICIs) and best combination regimen for people with advanced hepatocellular carcinoma (HCC) and to explore the predictive performance of tumour mutation burden (TMB).

To systematically evaluate the efficacy and safety of anaplastic lymphoma kinase (ALK) inhibitors in ALK-rearranged positive non-small cell lung cancer (NSCLC) with brain metastases, and update the overall survival (OS) outcomes of the second-generation and third-generation ALK (ALK-2ndG/3rdG) inhibitors versus first-generation (ALK-1stG) inhibitors.

Polycystic ovary syndrome (PCOS) remains the most common female reproductive endocrine disorder. Genetic studies have predominantly focused on the role of the nuclear genome, while the contribution of mitochondrial genetics in PCOS remains largely unknown.

Previous studies have reported the prognostic value of p53 upregulated modulator of apoptosis (PUMA) in numerous human tumors, but the conclusions have not been consistent. Therefore, this meta-analysis and the Cancer Genome Atlas (TCGA) data analysis were performed to estimate the prognostic significance of PUMA in solid tumors.

Serous ovarian cancer is the most common subtype of epithelial ovarian carcinoma-the most prevalent type of ovarian cancer. High-grade serous ovarian carcinoma (HGSOC) is thought to arise from the distal fallopian tube, with a precursor lesion known as serous tubal intraepithelial carcinoma (STIC). STICs are found in the final pathology of a salpingectomy specimen in 10%-20% of women with a BRCA gene mutation and 1%-7% of women without a mutation. However, there is currently no official guideline and a paucity of data on the management of STICs.

Platinum-based chemotherapy (PBC) remains the mainstay of treatments for triple-negative breast cancer (TNBC). TNBC is a heterogeneous group, the issue of whether BRCA1/2 mutation carriers have a particular sensitivity to platinum agents is inconclusive. We conducted a meta-analysis to explore the relationship between BRCA1/2 mutation and PBC susceptibility in individuals with TNBC, aiming to gain more information on the size of the benefit of PBC in BRCA1/2 mutation carriers.

Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies.

Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome-wide significance level (P < 5 × 10-8 ) were used as instrumental variables from a genome-wide meta-analysis of 449 734 individuals. Summary-level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta-analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio [OR] 0.94, 95% confidence interval [CI]: 0.90-0.98), stomach cancer (OR 0.84, 95% CI: 0.73-0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87-0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers.

ALDH+ H1975 lung adenocarcinoma stem cells (LSCs) are a rare cell population identified in lung adenocarcinoma (LUAD). LSCs can self-renew, drive tumor initiation, growth, metastasis, and recurrence and are also the predominant cause of poor prognosis due to their intrinsic resistance to drugs and chemotherapy. Consequently, LSCs are a promising target for LUAD therapy. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), exert many significant regulatory functions in the pathogenesis of human cancers, showing the necessity for a comprehensive understanding of the mechanisms that underlie lung carcinogenesis. Nonetheless, research on many known transcripts and messenger RNAs (mRNAs) has already generated new information. Unknown biomarkers in ncRNAs and systematic and comprehensive interrelation with unknown ncRNAs and mRNAs may provide further insights into the biology of LUAD. Herein, a set of novel ncRNAs that include miRNAs, lncRNAs, and circRNAs were identified, and differentially expressed patterns of ncRNAs and mRNAs in LSCs and ALDH-H1975 LUAD tumor cells (LTCs) were obtained using stringent bioinformatics pipelines. Through a meta-analysis of the identified landscapes, novel competitive endogenous RNA (ceRNA) networks were constructed to reveal the potential molecular mechanisms that regulate the hallmarks of LSCs and LTCs. This study presents a summary of novel ncRNAs and the fundamental roles of differentially expressed ncRNAs implicated in the activity of LSCs and LTCs. In addition, the study also provides a comprehensive resource for the future identification of diagnostic, therapeutic, and prognostic biomarkers in LUAD.

Patients with malignancies including malignant gliomas have a relatively high risk for venous thromboembolism (VTE). Recent evidence has linked isocitrate dehydrogenase (IDH) mutation with reduced VTE risk in malignant glioma. This meta-analysis aims to quantify the association of IDH mutation status with risks of VTE in patients with glioma.

To provide theoretical support for clinical diagnosis of lung cancer through an overview of systematic reviews (SRs) of the diagnostic value of miRNA.

Circulating microRNAs (miRNAs) are potential diagnostic biomarkers for breast cancer (BC). The application of miRNA panels could improve the performance of screening tests. Here, we integrated bioinformatic tools and meta-analyses to select circulating miRNAs with high diagnostic accuracy and combined these markers to develop diagnostic panels for BC.

Lynch syndrome (LS) predisposes affected individuals to a high lifetime risk of malignancies, including colorectal, endometrial, gastric, and duodenal cancers. The role of upper GI (UGI) cancer screening in LS has been uncertain, but recent studies have evaluated its utility.

Tumor suppressor genes (TSGs) are essential genes in the development of cancer. While they have many roles in normal cells, mutation and dysregulation of the TSGs result in aberrant molecular processes in cancer cells. Therefore, understanding TSGs and their roles in the oncogenic process is crucial for prevention and treatment of cancer. In this research, multi-omics breast cancer data were used to identify molecular mechanisms of TSGs in breast cancer. Differentially expressed genes and differentially coexpressed genes were identified in four large-scale transcriptomics data from public repositories and multi-omics data analyses of copy number, methylation and gene expression were performed. The results of the analyses were integrated using enrichment analysis and meta-analysis of a p-value summation method. The integrative analysis revealed that TSGs have a significant relationship with genes of gene ontology terms that are related to cell cycle, genome stability, RNA processing and metastasis, indicating the regulatory mechanisms of TSGs on cancer cells. The analysis frame and research results will provide valuable information for the further identification of TSGs in different types of cancers.