The RAD51 family of genes play a crucial role in the repair of DNA damage, and increasing evidence suggests a close link between the aberrant expression of RAD51 family genes and the development of breast cancer. However, their prognostic and clinical relevance remains subjects of ongoing debate. This study aims to systematically investigate the relationship between the overexpression of RAD51 family genes and breast cancer prognosis, as well as their association with clinicopathological characteristics, through a comprehensive meta-analysis. PubMed, EMBASE, OVID, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies published up to August 25, 2024. Two independent researchers screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data. Statistical analyses were conducted using the Meta package in R 4.2.2. Thirteen studies comprising 20,222 breast cancer patients were included. High expression of RAD51 family genes was associated with poorer overall survival (OS) [HR = 1.305, 95%CI (1.145-1.488), P < 0.01], disease-free survival/distant metastasis-free survival (DFS/DMFS) [HR = 1.588, 95%CI (1.208-2.089), P < 0.01], and disease-specific survival (DSS) [HR = 1.403, 95%CI (1.066-1.846), P = 0.02]. In addition, subgroup analyses further showed that high RAD51 expression was associated with worsened OS [HR = 1.475, 95%CI (1.275-1.706), P < 0.01], DFS [HR = 1.584, 95%CI (1.133-2.215), P < 0.01] and progression-free survival (PFS) [HR = 2.439, 95%CI (1.172-5.075), P = 0.02]. In contrast, high expression of RAD51 paralogs was linked to improved PFS prognosis [HR = 0.870, 95%CI (0.797-0.949), P < 0.01]. Regarding clinical characteristics, high expression of RAD51 family genes was significantly associated with human epidermal growth factor receptor 2 (HER2) positivity [OR = 1.782, 95%CI (1.328-2.392), P < 0.01]. The overexpression of RAD51 family genes is correlated with unfavorable prognosis in breast cancer and exhibits a strong association with HER2-positive subtypes. These findings underscore the potential of RAD51 family genes as prognostic biomarker and therapeutic targets in breast cancer management.

PD-L1 expression is an important biomarker for the management of non-small cell lung cancer (NSCLC) but has been highly heterogeneous across studies. We developed a statistical model to reconcile conflicting estimates of PD-L1 prevalence by accounting for between-study variation in test sensitivity, specimen age, and laboratory count. In doing so, we obtained refined estimates for PD-L1 expression prevalence and identified differences by histological subtype, mutational status, and stage. Across 92 studies published between 2015 and 2023, the detectability of PD-L1 declined with increasing specimen age while the consistency of detection rates was greater for studies incorporating data from a higher number of laboratories. Using the 22C3 antibody as a benchmark, we predicted that 58.3% (95% CrI 49.8-66.1%) and 27.0% (95% CrI 21.2-33.1%) of NSCLC will have PD-L1 tumour proportion scores at the ≥ 1% and ≥ 50% threshold. PD-L1 expression was lower in EGFR-mutated NSCLC and higher in NSCLC with ALK, KRAS, MET, ROS1, and RET alterations. PD-L1 expression was more common with later-stage disease. Overall, this work highlights the continuing challenge of consistency in PD-L1 testing. Although the underlying prevalence of PD-L1 expression varies in the lung cancer population based on tumour-related factors, controllable differences in testing parameters also account for variations in PD-L1 prevalence.

The causes of bladder cancer are not completely understood. Our objective was to identify blood proteins and modifiable causal risk factors for bladder cancer by combining genome-wide association study (GWAS) and Mendelian randomization (MR) analyses.

Circulating tumor DNA (ctDNA) is an emerging biomarker in malignant melanoma(MM), and high levels of ctDNA may reflect a higher tumor load. However, its prognostic value for MM receiving immune checkpoint inhibitors(ICI) remains controversial. This meta-analysis aimed to elucidate the prognostic significance of ctDNA in this patient population.

Cell dedifferentiation is considered an important hallmark of cancer. The atavistic reversal to a unicellular-like (UC) state is a less widely accepted concept, so far not included in the conventional hallmarks. The activated expression of ontogenetically earlier and evolutionary earlier genes in cancers supports both theories because ontogenesis partially recapitulates phylogenesis during cell differentiation (the cellular biogenetic law). We directly contested both types of gene signatures in stem vs. differentiated and cancer vs. normal cells, using meta-analysis of human single-cell transcriptomes (totally, 38 pairwise comparisons involving over 18,600 cells). Because compared cells can differ in proliferation rate, the correction for cell cycle activity was applied. Taken together as multiple variables in stem vs. differentiated cells analyses, the ontogenetic signature excluded the UC signature from predictive variables, usually even forcing it to change the sign of prediction (from plus to minus). In contrast, in cancer vs. normal cells, the UC signature excluded the ontogenetic signature. Thus, the direct contest decided in favor of the atavistic theory and placed a UC-like state as a central hallmark of cancer, which has a plausible evolutionarily formed mechanism (UC attractor) and can generate other hallmarks. These data suggest a paradigm shift in the understanding of oncogenesis and propose an integrative framework for cancer research. In a practical sense, the upregulation of UC signature over ontogenetic signature indicates potential tumorigenicity, which can be used in early diagnostics and regenerative medicine. For therapy, these results suggest the UC center of cellular networks as a universal target.

IDH-wildtype glioblastoma multiforme (GBM) and grade 4 IDH-mutant astrocytoma are challenging to manage in oncology. This study explores the contrast between gross total resection (GTR) and supratotal resection (SupTR) for IDH-wildtype GBM and grade 4 IDH-mutant astrocytoma, aiming to summarize their influence on crucial clinical outcomes.

Endometrial cancers can be classified into 4 molecular sub-groups: (1) POLE mutated (POLEmut), (2) mismatch repair deficiency/microsatellite-instable (MMRd/MSI-H), (3) TP53-mutant or p53 abnormal (p53abn), and (4) no specific mutational profile (NSMP). Although molecular classification is increasingly applied in oncology, its role in guiding fertility-sparing treatments for endometrial cancer remains unclear. This study examines the prognostic role of molecular classification in fertility-sparing treatment and its potential to guide treatment decisions.

DNA hypomethylation and uracil misincorporation into DNA, both of which have a very important correlation with colorectal carcinogenesis. Folate plays a crucial role in DNA synthesis, acting as a coenzyme in one-carbon metabolism, which involves the synthesis of purines, pyrimidines, and methyl groups. MTHFR, a key enzyme in folate metabolism, has been widely studied in relation to neural tube defects and hypertension, but its role in colorectal cancer remains underexplored. Therefore, understanding the role of folate and MTHFR genes in colorectal cancer may be helpful for potential preventive or therapeutic interventions. In this meta-analysis, the effects of MTHFR genotype and folate intake on colorectal cancer incidence were analyzed.

To address the issue that most microsatellite-stable (MSS) and proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) patients have minimal response to immunotherapy, this meta-analysis evaluated the efficacy and safety of durvalumab and tremelimumab with concomitant treatment in treating MSS/pMMR metastatic colorectal cancer.

Lung cancer (LC) is the leading cause of cancer-related death in humans. tRNA-derived small RNA (tsRNA) is a novel biomarker that plays a crucial role in the genesis and development of LC. In this study, we aimed to investigate the value of differentially expressed tsRNAs in LC through meta-analysis.

MAP2K1/MEK1 mutations are potentially actionable drivers in cancer. MAP2K1 mutations have been functionally classified into three groups according to their dependency on upstream RAS/RAF signaling. However, the clinical efficacy of mitogen-activated protein kinase (MAPK) pathway inhibitors (MAPKi) for MAP2K1-mutant tumors is not well defined. We sought to characterize the genomic and clinical landscape of MAP2K1 mutant tumors to evaluate the relationship between MAP2K1 mutation class and clinical activity of MAPKi.

Glioblastoma multiforme (GBM) is an aggressive brain tumor. This meta-analysis investigates the association between HOTAIR expression levels and GBM.

Multi-gene panel testing allows efficient detection of pathogenic variants in cancer susceptibility genes including moderate-risk genes such as ATM and PALB2. A growing number of studies examine the risk of breast cancer (BC) conferred by pathogenic variants of these genes. A meta-analysis combining the reported risk estimates can provide an overall estimate of age-specific risk of developing BC, that is, penetrance for a gene. However, estimates reported by case-control studies often suffer from ascertainment bias. Currently, there is no method available to adjust for such bias in this setting. We consider a Bayesian random effect meta-analysis method that can synthesize different types of risk measures and extend it to incorporate studies with ascertainment bias. This is achieved by introducing a bias term in the model and assigning appropriate priors. We validate the method through a simulation study and apply it to estimate BC penetrance for carriers of pathogenic variants in the ATM and PALB2 genes. Our simulations show that the proposed method results in more accurate and precise penetrance estimates compared to when no adjustment is made for ascertainment bias or when such biased studies are discarded from the analysis. The overall estimated BC risk for individuals with pathogenic variants are (1) 5.77% (3.22%-9.67%) by age 50 and 26.13% (20.31%-32.94%) by age 80 for ATM; (2) 12.99% (6.48%-22.23%) by age 50, and 44.69% (34.40%-55.80%) by age 80 for PALB2. The proposed method allows meta-analyses to include studies with ascertainment bias, resulting in inclusion of more studies and thereby more accurate estimates.

In 2013, The Cancer Genome Atlas Research Network suggested that endometrial carcinoma patients may be reclassified into four molecular prognostic groups.

Some cancer patients derive limited benefit from anti-angiogenic therapy or discontinuation due to adverse reactions. Vascular endothelial growth factor receptor 2 (VEGFR2) plays an important role in regulating angiogenesis in tumors. This study aims to evaluate the association of VEGFR2 polymorphisms with clinical outcomes of anti-angiogenic drugs (AADs) in cancer patients.

Intestinal-type gastric cancer (IGC) and diffuse-type gastric cancer (DGC) exhibit different prevalence rates between sexes. While environmental factors like Helicobacter pylori infection and alcohol consumption contribute to these differences, they do not fully account for them, suggesting a role for host genetic factors.

Background/Objectives: Salivary gland carcinomas encompass a broad group of malignant lesions characterized by varied prognoses. Stem cells have been associated with the potential for self-renewal and differentiation to various subpopulations, resulting in histopathological variability and diverse biological behavior, features that characterize salivary gland carcinomas. This study aims to provide a thorough systematic review of immunohistochemical studies regarding the expression and prognostic significance of stem cell markers between different malignant salivary gland tumors (MSGTs). Methods: The English literature was searched via the databases MEDLINE/PubMed, EMBASE via OVID, Web of Science, Scopus, and CINHAL via EBSCO. The Joanna Briggs Institute Critical Appraisal Tool was used for risk of bias (RoB) assessment. Meta-analysis was conducted for markers evaluated in the same pair of diseases in at least two studies. Results: Fifty-four studies reported the expression of stem cell markers, e.g., c-KIT, CD44, CD133, CD24, ALDH1, BMI1, SOX2, OCT4, and NANOG, in various MSGTs. Low, moderate, and high RoB was observed in twenty-five, eleven, and eighteen studies, respectively. Meta-analysis revealed an outstanding discriminative ability of c-KIT for adenoid cystic carcinoma (AdCC) over polymorphous adenocarcinoma [P(LG)A] but did not confirm the prognostic significance of stem cell markers in MSGTs. Conclusions: This study indicated a possible link between stem cells and the histopathological heterogeneity and diverse biological behavior that characterize the MSGTs. c-KIT might be of diagnostic value in discriminating between AdCC and P(LG)A.

Pancreatic cancer (PC) remains a significant contributor to global cancer mortality, with limited effective diagnostic and prognostic tools. MicroRNAs (miRNAs) have emerged as promising biomarkers for PC diagnosis and prognosis. A comprehensive literature search was conducted in PubMed, Web of Science, and Scopus. Studies reporting sensitivity, specificity or area under the curve (AUC) for miRNAs in PC diagnosis, as well as hazard ratios (HRs) for survival evaluations, were included. Data extraction and quality assessment followed PRISMA guidelines. Meta-analyses were conducted using appropriate statistical methods. The protocol is registered in PROSPERO. Diagnostic analysis included 290 evaluations, revealing an overall AUC of 0.8226 for PC diagnosis. Subgroup analyses showed varying accuracies, with blood and tissue specimens yielding higher AUC values. Promising miRNAs with AUC values above 0.8 included miR-320, miR-1290, miR-93, miR-25, miR-451, miR-20, miR-21, miR-223 and miR-122. Prognostic analysis encompassed 46 studies, indicating significant associations between miRNA expression and overall survival (OS) and progression-free survival (PFS). The combined HR for studies reporting OS HRs higher than one was 1.7613 (95% CI: 1.5394-2.0152, p < 0.0001; I2 = 81.7%). Notable miRNAs with prognostic significance included miR-10, miR-21 and miR-221. Studies reporting OS HRs less than one had a pooled HR of 0.6805 (95% CI: 0.5862-0.7901, p < 0.0001; I2 = 65.4%). MiRNAs hold promise as diagnostic and prognostic biomarkers for PC. Blood and tissue specimens offer superior diagnostic accuracy, and several miRNAs show potential for predicting patient outcomes.

Malignant gliomas are the most aggressive brain tumors with no certain therapeutic methods. Nowadays, novel treatment methods are introduced for gliomas among which gene therapy is known as a promising and robust method. In this method, genes with key roles in the prevention of cell cycle or induction of cell suicide are transferred to the tumor site using vectors. Viral vectors are the most popular transfer methods, while the liposomes are also used for gene therapy.

Recently, microRNAs (miRNAs) have been applied as biomarkers for diffuse large B-cell lymphoma (DLBCL) patients. Early diagnosis and management of DLBCL can improve patient survival and prognosis.