DDX41 is one of the most frequently altered genes in familial acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Mutation of DDX41 has been widely reported in various types of myeloid neoplasms. This systematic review and meta-analysis were conducted to assess the clinical characteristics and relationship between DDX41 mutations and OS in myeloid neoplasm patients. We thoroughly searched the PubMed, the Cochrane Library, Embase, Web of Science, MEDLINE, and Google Scholar databases. Two reviewers separately reviewed and extracted the data. Twenty studies totaling 9,058 patients have been integrated into the meta-analysis. The extensive pooled analysis showed a significant association between DDX41 mutations and improved OS (HR 0.70, 95% CI 0.52-0.93, P = 0.01). Subgroup analysis confirmed that DDX41 mutation operated to be a reliable positive indicator of OS when subdivided by different types of myeloid neoplasms. In terms of the clinicopathological value, DDX41 mutations were significantly correlated with the male sex. Age, AML prevalence, bone marrow, or white blood cell counts did not correlate with any findings. The top three genetic variants were p.M1I, p.D140fs, and p.R525H. Co-mutations in patients with DDX41 mutations most commonly include the following: additional sex combs-like 1 (ASXL1), DNA methyltransferase 3 A (DNMT3A), tumor protein p53 (TP53), ten-eleven translocation 2 (TET2) and serine/arginine-rich splicing factor 2 (SRSF2). Our results substantiate that DDX41 mutations were associated with significantly good OS and provide more insight into the clinicopathological characteristics of DDX41 mutations in individuals with myeloid neoplasms.

We aimed to answer the following question: How effective is the addition of AKT inhibitors to the treatment of advanced or metastatic breast cancer?

Intracranial meningiomas are the most common primary tumors of the central nervous system. Although generally benign, some genetic alterations can induce aggressive behavior characterized by higher recurrence rates and reduced survival.

Acquired MET alterations is one of the resistance mechanisms to advanced NSCLC patients treated with EGFR tyrosine kinase inhibitors (TKIs). Several clinical trials combined MET-TKI (such as capmatinib, tepotinib, savolitinib) with EGFR-TKI to overcome MET alterations resistance. We performed this meta-analysis to determine the efficacy and safety of MET-TKI plus EGFR-TKI combined therapy in NSCLC patients.

Given the known relationship between CDKN2A homozygous deletion (HD) and worsened outcomes in both meningiomas and IDH-mutant astrocytomas, it is paramount to identify CDKN2A HD for accurate risk stratification of patients. Multiple array platforms can detect CDKN2A HD. However, these methods are expensive and are not readily available at every institution. To address this, we conducted a meta-analysis and literature review to evaluate 5'-methylthioadenosine phosphorylase (MTAP) expression determined by immunohistochemistry (IHC) as a surrogate of CDKN2A HD. Our study analyzed 7 cohort studies, 3 of which focused on meningiomas encompassing a total of 87 patients; and 4 studies were conducted on infiltrating glioma patients, consisting of 423 patients. Our results show that despite utilizing different MTAP IHC clones, the results among all studies showed consistently good sensitivity and specificity. The overall sensitivity and specificity of MTAP IHC as a surrogate of CDKN2A HD was excellent with 92.3% and 97.5%, respectively. These results were maintained when MTAP IHC was evaluated in distinct tumor types. MTAP IHC is a good surrogate marker for identifying CDKN2A HD in infiltrating gliomas and meningiomas. MTAP IHC implementation would allow correct integrated diagnosis for institutions that lack DNA sequencing.

Metastatic castration-resistant prostate cancer (mCRPC) patients with BRCA1/2 mutations show significant responses to poly-ADP ribose polymerase inhibitors (PARPi), while the efficacy of these agents in patients with homologous recombination repair (HRR) gene alterations other than BRCA remains unclear.

Multiple myeloma ranks as the second most common hematopoietic malignancy in terms of both incidence and mortality. Prognostic stratification is critical for optimizing therapeutic strategies, as certain genetic alterations can significantly influence disease progression and treatment response. The meta-analysis analyzed data from 3421 multiple myeloma patients and 14,720 controls. PubMed, Web of Science, and Scopus were used as databases. Associations between the SNPs and multiple myeloma were calculated as a measure of pooled odds ratios (ORs) and 95% confidence intervals. Statistical analysis was performed using Review Manager (RevMan). DNAH11 rs4487645 A/C genotype (OR = 1.35; 95% CI: 1.24-1.46; p < 0.00001; I2 = 0%), ULK4 rs1052501 G/G genotype (OR = 1.21; 95% CI: 0.98-1.50; p = 0.08; I2 = 64%), ULK4 rs1052501 A/G genotype (OR = 1.23; 95% CI: 1.13-1.34; p < 0.00001; I2 = 0%), DTNB rs6746082 A/A genotype (OR = 1.10; 95% CI: 1.01-1.20; p = 0.03; I2 = 45%), and VDR rs1544410 A/G genotype (OR = 1.87; 95% CI: 1.04-3.36; p = 0.04; I2 = 0%) increased multiple myeloma risk. Our study concludes that DNAH11, ULK4, DTNB, and VDR may serve as predictive biomarkers for MM risk.

B7H3 (CD276), an immunoregulatory molecule known for its role in immune evasion by transmitting inhibitory signals to T lymphocytes, has garnered significant attention in recent years as a promising target for cancer immunotherapy. This interest is largely due to its high expression in various types of solid tumors, coupled with low protein levels in normal tissues. However, studies examining the impact of B7H3 on survival outcomes have shown inconsistent results, leaving its prognostic significance not fully clarified. Therefore, this meta-analysis aimed to assess the relationship between B7H3 expression and various prognostic parameters in patients with solid malignancies. PubMed, Web of Science (WOS), Cochrane, SCOPUS, and Embase databases were searched for eligible articles published until November 2024. Statistical analysis was performed using R studio (version 4.3.2). The analysis included a total of 51 eligible studies comprising 11,135 patients. Results showed that overexpression of B7H3 is a negative predictor for all examined survival outcomes: OS (HR = 1.71, 95% CI = 1.44-2.03, p < 0.0001), DFS (HR = 2.02, 95% CI = 1.49-2.73, p < 0.0001), PFS (HR = 2.10, 95% CI = 1.44-3.06, p < 0.0001), RFS (HR = 1.66, 95% CI = 1.11-2.48, p = 0.01), and DSS (HR = 1.70, 95% CI = 1.24-2.32, p < 0.01). Despite the high heterogeneity observed across the studies, the sensitivity analysis confirmed the robustness of these results. This research suggests that B7H3 may serve as an effective biomarker for prognosis in solid tumors.

Angiopoietin-like protein 4 (ANGPTL4) plays a crucial role in processes such as angiogenesis, inflammation, and metabolism. Despite numerous studies suggesting its involvement in cancer, a definitive role remains unclear. We introduce the first comprehensive meta-analysis and pan-cancer bioinformatics study on ANGPTL4, aiming to unravel its implications across various cancer types.

Extramammary Paget's disease (EMPD) is a neoplastic condition primarily in the anogenital region. A subset of cases exhibits HER2 expression, generally associated with poor prognosis. This paper aimed to systematically explore the potential correlation between HER2 expression, clinicopathological features and prognosis in EMPD.

Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses (n = 6,095-246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria.

The efficacy and safety of pemigatinib in advanced cholangiocarcinoma (aCCA) were presented in phase I-II trials and retrospective reports, with small sample sizes and variable results.

This meta-analysis investigates the association between acute lymphoblastic leukemia (ALL) susceptibility and IKZF1 gene SNPs.

PD-(L)1 inhibitors have shown benefit in mismatch repair-deficient (MMRd) endometrial cancer. However, their efficacy in mismatch repair-proficient endometrial cancer (comprising POLE-mutated (POLEmut), p53-abnormal (p53abn), and no-specific-molecular-profile (NSMP) molecular classes) remains unclear. This systematic review and meta-analysis evaluated the efficacy of PD-(L)1 inhibitors, as monotherapy or combined with chemotherapy, across the 4 molecular classes.

The association between microRNA 17-92 cluster host gene (MIR17HG) polymorphisms and the risk of cancer has been evaluated in studies, here, we attempted to elucidate the relationship between 6 single nucleotide polymorphisms (SNPs) of MIR17HG (rs17735387 G > A, rs7336610 C > T, rs1428 C > A, rs7318578 A > C, rs72640334 C > A, and rs75267932 A > G), 3 SNPs in the promoter of MIR17HG (rs9588884 C > G, rs982873 T > C, and rs1813389 A > G) and susceptibility to cancer in Chinese Han population.

Microsatellite instability (MSI), caused by defects in mismatch repair (MMR) genes, serves as a critical molecular biomarker with therapeutic implications for endometrial cancer (EC). This study aims to assess the diagnostic performance of radiomics as a non-invasive approach for predicting MSI status in EC.

Tumor mutations and the composition of the tumor microenvironment have prognostic and therapeutic significance in colorectal cancer (CRC). However, immunotherapy remains a challenge for patients with proficient mismatch repair (pMMR) CRC. In this paper, the association between tumor-infiltrating lymphocytes (TILs) and tumor mutations on survival outcomes in patients with localized pMMR CRC was examined.

In patients with solid tumors undergoing neoadjuvant immune checkpoint inhibitor (ICI) therapy, identifying biomarkers to predict pathologic complete response (pCR) preoperatively could enhance treatment modulation. Circulating tumor DNA (ctDNA) clearance is a potential predictor of pCR, though its analytical and clinical validity has yet to be established. This systematic review and meta-analysis aims to assess the role of ctDNA clearance as a predictor of pCR in patients with solid tumors treated with neoadjuvant ICIs.

Despite the crucial role of T cell clones in anti-tumor activity, their characterization and association with clinical outcomes following immune checkpoint inhibitors are lacking. Here, we analyzed paired single-cell RNA sequencing/T cell receptor sequencing of 767,606 T cells across 460 samples spanning 6 cancer types. We found a robust signature of response based on expanded CD8+ clones that differentiates responders from non-responders. Analysis of persistent clones showed transcriptional changes that are differentially induced by therapy in the different response groups, suggesting an improved reinvigoration capacity in responding patients. Moreover, a gene trajectory analysis revealed changes in the pseudo-temporal state of de novo clones that are associated with clinical outcomes. Lastly, we found that clones shared between tumor and blood are more abundant in non-responders and execute distinct transcriptional programs. Overall, our results highlight differences in clonal transcriptional states that are linked to patient response, offering valuable insights into the mechanisms driving effective anti-tumor immunity.

Observational studies still cannot establish a causal relationship between plasma caffeine levels and cancer risk. This study aimed to investigate the genetic effects of plasma caffeine levels on cancer risk through Mendelian randomization (MR).