Colorectal cancer is one of the most common and lethal malignancies, and various factors have been confirmed to contribute to its occurrence. However, the causal role of immune cell-specific changes in the development of colorectal cancer has not been investigated. The bidirectional two-sample Mendelian randomization analysis was performed to explore the association between 731 types of immune cell phenotypes-specific changes and colorectal cancer. The inverse variance weighting results indicated that a total of 31 and 28 immune cell phenotypes significantly associated with colorectal cancer in two different datasets, respectively. The primary results of inverse variance weighting Mendelian randomization suggested that the immune cell phenotypes BAFF-R on IgD+ CD38dim (OR = 1.033, 95%CI: 1.005-1.062) and SSC-A on monocyte (OR = 1.055, 95%CI: 1.016-1.096) served as risk factor for colorectal cancer. In addition, the meta-analysis further supports the causal link of BAFF-R on IgD+ CD38dim (pooled OR = 1.035, 95%CI: 1.013-1.059) and SSC-A on monocyte (pooled OR = 1.060, 95%CI: 1.026-1.095) with colorectal cancer. Finally, the inverse variance weighting Mendelian randomization result suggested that genetic determinants of colorectal cancer may decrease the level of HLA DR++ monocyte absolute count (OR = 0.686, 95%CI: 0.508-0.925). Our results indicated that the potential causal association of BAFF-R on IgD+ CD38dim and SSC-A on monocyte with colorectal cancer. The identified immune cells may be appealing drug targets for colorectal cancer, but lack confirmation from real clinical evidence. Further studies are needed to investigate the roles of these immune cells in colorectal cancer.

Intrahepatic cholangiocarcinoma is a public health threat because of its aggressiveness. Its genetic background differs from other biliary cancers. The aim of this study was to investigate the impact of genetic alterations on long-term outcomes.

The activity of osimertinib is not fully characterized in non-small-cell lung cancer (NSCLC) with uncommon epidermal growth factor receptor (EGFR) mutations. Therefore, we conducted a systematic review and meta-analysis to assess the safety and efficacy of osimertinib in patients with NSCLC harboring uncommon somatic EGFR mutations.

Circulating tumour DNA (ctDNA) has emerged as a valuable liquid biopsy biomarker in the field of oncology, including head and neck squamous cell carcinomas (HNSCCs), offering potential insights into cancer diagnosis, progression, and prognosis. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in HNSCC.

The genetic causal association between the mitochondrial DNA copy number (mtDNA-CN) and the development of glioma and glioblastoma (GBM) remains unclear.

CD147 belongs to the immunoglobulin superfamily, also known as Basigin (BSG), and is a highly glycosylated single transmembrane glycoprotein present in various tissues. Meta and bioinformatic analyses were used to explore the correlation between CD147 expression and the clinicopathological characteristics prognosis of breast cancer.

Genetic variants associated with molecular traits that are also associated with liability to glioma can provide causal evidence for the identification and prioritisation of drug targets.

Several studies have shown that the long noncoding RNA (lncRNA) CBR3-AS1 is overexpressed in various cancers and is playing an oncogene role. This meta-analysis aims to elucidate the relationship between lncRNA CBR3-AS1 expression and the prognosis and clinicopathological features of cancer patients.

Colorectal cancer is the third most common malignancy in the USA and accounts for more than 1 million deaths worldwide with screening shown to reduce CRC mortality. This meta-analysis analyzed the use of stool DNA for screening average risk, asymptomatic subjects for colorectal cancer and advanced precancerous lesions and compared sDNA to FOBT tests (gFOBT and FIT). Eight studies were included from four different countries with a total of 39 665 subjects. Pooled sensitivity and specificity for sDNA for detecting CRC was 83.3% (95% CI: 60.8-94.2) and 92.4% (95% CI: 90.1-94.1), respectively, compared with FOBT, which had a lower sensitivity at 70.2% (95% CI: 45.5-86.9) but higher specificity 95.7% (95% CI: 95.1-96.2). Further analysis showed improved sensitivity of sDNA to 92.6% when only the studies employing sDNA tests that incorporate hemoglobin immunochemical test were used. Both sDNA and FOBT tests had low sensitivity for detecting advanced precancerous lesions. sDNA tests are sensitive and specific for the detection of CRC but show low sensitivity compared with colonoscopy for the detection of advanced precancerous lesions.

B-cell acute lymphoblastic leukaemia (B-ALL) and T-cell acute lymphoblastic leukaemia (T-ALL) are both types of acute lymphoblastic leukaemia (ALL), which is a cancer of the blood and bone marrow characterized by the rapid proliferation of immature lymphocytes. In ALL, CDKN gene deletions have been extensively studied regarding their prognostic significance. The purpose of this meta-analysis is to determine whether there is a consistent relationship between CDKN gene variations and the incidence of lymphocytic leukaemia.

Ultra-low-pass whole-genome sequencing (ULP-WGS) (≤0.5 × coverage) of plasma cell-free DNA (cfDNA) has emerged as a low-cost, promising tool to assess the circulating tumor DNA (ctDNA) fraction. This meta-analysis aims to summarize the current findings and comprehensively investigate the prognostic value of baseline ctDNA detected by ULP-WGS in solid tumors. A systematic review was carried out by searching PubMed/MEDLINE and Scopus databases to identify eligible studies conducted between January 2014 and January 2024. Inclusion criteria comprised studies with reported overall survival and progression-free survival outcomes across therapy-naïve patients with different solid tumors. All patients underwent baseline ULP-WGS of plasma cfDNA and were categorized as ctDNA positive (tumor fraction ≥10%) or negative (tumor fraction <10%). A one-stage meta-analysis was performed using patient-level survival data reconstructed from published articles. A Cox proportional hazards model with shared frailty was used to assess the difference in survival between arms. A total of six studies, comprising 620 patients (367 negative ctDNA and 253 positive ctDNA), were included in the overall survival analysis, while five studies, involving 349 patients (212 negative ctDNA and 137 positive ctDNA), were included in the progression-free survival analysis. The meta-analysis showed that patients with baseline positive ctDNA had a significantly higher risk of death (HR = 2.60, 95% CI: 2.01-3.36) and disease progression (HR = 2.28, 95% CI: 1.71-3.05) compared to those with negative ctDNA. The presence of a positive ctDNA at baseline is associated with increased risk of death and progression in patients with same-stage cancer.

Interleukins (ILs) play a significant role in triggering the inflammatory response in blood vessels and immune cells. A systematic review and meta-analysis were conducted to investigate the relationship between IL-8 (rs4073), IL-13 (rs1800925), IL-22 (rs1179251, rs1179246, and rs2227485), and IL-27 (rs17855750 and rs153109) polymorphisms and the risk of developing colorectal cancer (CRC). Four databases were searched up until October 13, 2023, without any restrictions, to find relevant studies. The association was evaluated using crude odds ratios (ORs) and 95% confidence intervals in five genetic models. A total of twenty-three articles were entered into the meta-analysis. The pooled ORs (p-values) for the IL-8 (rs4073) polymorphism were 0.98 (0.63), 0.93 (0.44), 0.89 (0.13), 0.94 (0.38), and 0.99 (0.90) for studies following HWE without heterogeneity, and for all studies with high heterogeneity were 1.03 (0.69), 1.30 (0.07), 1.04 (0.71), 1.12 (0.20), and 1.23 (0.06). For the IL-13 (rs1800925) polymorphism, the pooled ORs were 1.44 (0.06), 2.58 (0.0004), 1.72 (0.16), 1.82 (0.09), and 2.37 (0.001) in AHHDR models, respectively. The pooled ORs of IL-22 (rs1179251) polymorphism for AHHDR models were 0.97 (0.92), 0.92 (0.90), 0.98 (p = 0.95), 1.08 (0.87), and 0.96 (0.82), respectively. The pooled ORs of IL-22 (rs1179246) polymorphism for AHHDR models were 0.98 (0.67), 0.97 (0.80), 0.92 (0.36), 0.93 (0.42), and 1.02 (0.84), respectively. The pooled ORs of IL-22 (rs2227485) polymorphism for AHHDR models were 1.47 (0.02), 2.03 (0.02), 1.28 (0.29), 1.52 (0.06), and 1.70 (0.04), respectively. The pooled ORs of IL-27 (rs17855750) polymorphism for AHHDR models were 0.53 (0.46), 0.19 (0.28), 1.10 (0.60), 0.55 (0.58), and 0.27 (p = 0.05), respectively. The pooled ORs of IL-27 (rs153109) polymorphism for AHHDR models were 1.28 (0.007), 1.45 (0.002), 1.40 (0.0002), 1.41 (< 0.0001), and 1.20 (0.09), respectively. The results reported that just the TT genotype of IL-13 (rs1800925), the T allele and TT genotype of IL-22 (rs2227485), and the G allele and GG, AG and GG + AG genotypes of IL-27 (rs153109) polymorphisms had an elevated risk in CRC patients.

Risk reduction salpingo-oophorectomy (RRSO) is usually performed in women with hereditary breast and ovarian cancer (HBOC) syndrome for BRCA1 and BRCA2 gene mutation carriers, resulting in surgical menopause, which is more associated with a high risk of cardiovascular and metabolic disease than in premenopausal and natural menopausal women. This study assessed the prevalence of cardiovascular and metabolic outcomes in women who underwent salpingo-oophorectomy as a preventive measure against HBOC. This meta-analysis assessed prevalence rates for four metabolic/cardiovascular conditions: myocardial infarction, hypertension, hypercholesterolemia, and type 2 diabetes mellitus. DerSimonian and Laird random-effects models were applied to all analyses, with 95% confidence interval (CI). Heterogeneity was assessed with I². We used OpenMeta Analyst software for statistical analysis. A total of five retrospective studies and one observational study involving 1,320 patients were included. The average body mass index (BMI) was 25.97 kg/m2 and the average waist circumference was 87.94 cm. The analysis across a mean 4.94-year follow-up revealed prevalence rates for acute myocardial infarction of 1.5% (95% CI 0.3-2.7; P = 0.077; I²=56.25%), hypertension of 28% (95% CI 6.9-49.1; P < 0.001; I2 = 98.42%), hypercholesterolemia of 27.2% (95% CI 6.8-47.6; P < 0.001; I²=98.67%), and type 2 diabetes mellitus of 3.3% (95% CI 1.1-5.5; P < 0.001; I²=82.44%). Our findings suggest that there is no marked increase in cardiovascular risk among women with HBOC undergoing RRSO.

We evaluated the impact of systematic bias due to loss of heterozygosity (LOH) and incomplete phenotyping in studies examining the relationship between CYP2D6 variants and breast cancer recurrence among women treated with tamoxifen.

Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is considered an important factor in the progression of cancer, acting as a modulator of cellular migration, adhesion, and metastatic potential. Its significance as a prognostic factor, however, remains unclear, which necessitated a comprehensive review and meta-analysis.

Myasthenia gravis (MG) is a rare autoantibody-mediated disease affecting the neuromuscular junction. We performed a genome-wide association study of 5708 MG cases and 432,028 controls of European ancestry and a replication study in 3989 cases and 226,643 controls provided by 23andMe Inc. We identified 12 independent genome-wide significant hits (P < 5e-8) across 11 loci. Subgroup analyses revealed two of these were associated with early-onset (at age <50) and four with late-onset MG (at age ≥ 50). Imputation of human leukocyte antigen alleles revealed inverse effect sizes for late- and early-onset, suggesting a potential modulatory influence on the time of disease manifestation. We assessed the performance of polygenic risk scores for MG, which significantly predicted disease status in an independent target cohort, explaining 4.21% of the phenotypic variation (P = 5.12e-9). With this work, we aim to enhance our understanding of the genetic architecture of MG.

To systematically evaluate the efficacy and safety of osimertinib plus bevacizumab in treating advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and EGFR-TKI combination treatments have become the standard first-line treatments for EGFR-mutated non-small cell lung cancer (NSCLC) patients. However, the best option has yet to be determined. This study compares the efficacy and safety of various first-line EGFR-TKI monotherapies and combination treatments for advanced EGFR-mutated NSCLC.

Aurora kinase A (AURKA) is a major regulator of the cell cycle. A prominent association exists between high expression of AURKA and cancer, and impairment of AURKA levels can trigger its oncogenic activity. In order to explore the contribution of post-transcriptional regulation to AURKA expression in different cancers, we carried out a meta-analysis of -omics data of 18 cancer types from The Cancer Genome Atlas (TCGA). Our study confirmed a general trend for increased AURKA mRNA in cancer compared to normal tissues and revealed that AURKA expression is highly dependent on post-transcriptional control in several cancers. Correlation and clustering analyses of AURKA mRNA and protein expression, and expression of AURKA-targeting hsa-let-7a miRNA, unveiled that hsa-let-7a is likely involved to varying extents in controlling AURKA expression in cancers. We then measured differences in the short/long ratio (SLR) of the two alternative cleavage and polyadenylation (APA) isoforms of AURKA mRNA across cancers compared to the respective healthy counterparts. We suggest that the interplay between APA and hsa-let-7a targeting of AURKA mRNA may influence AURKA expression in some cancers. hsa-let-7a and APA may also independently contribute to altered AURKA levels. Therefore, we argue that AURKA mRNA and protein expression are often discordant in cancer as a result of dynamic post-transcriptional regulation.

This study compared the safety and efficacy of osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), with those of other TKIs and its use alongside bevacizumab in patients with EGFR mutation-positive advanced non-small-cell lung cancer. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were used to conduct extensive searches for relevant randomized controlled trials until January 30, 2024. Osimertinib monotherapy favored disease control rate, whereas the comparator treatment arm favored overall survival. Using subgroup analysis, the objective response rate and progression-free survival (PFS) were significantly elevated by Osimertinib monotherapy compared with pemetrexed combined with carboplatin or cisplatin. The comparator treatment arm receiving gefitinib or erlotinib significantly favored progression-free survival and overall survival compared with osimertinib monotherapy. In patients treated with osimertinib monotherapy, the incidence of all adverse events (AEs) decreased compared with comparator treatment arm. Anemia was the only AE associated with osimertinib monotherapy. Pemetrexed combined with carboplatin or cisplatin resulted in greater loss of appetite than osimertinib monotherapy. The most associated AE of osimertinib monotherapy was diarrhea, according to network analysis. Although its efficacy is not consistent with other EGFR TKIs, osimertinib was associated with a decrease in AEs in patients with EGFR mutation-positive advanced non-small-cell lung cancer.