Despite advances in understanding thyroid cancer pathogenesis, the specific epigenetic mechanisms driving malignant transformation remain incompletely characterized. While genetic variations have been well documented, the role of DNA methylation, particularly involving tumor suppressor genes, represents a critical knowledge gap. This resaerch aimed to evaluate the methylation status of the tissue inhibitor of metalloproteinase 3 (TIMP-3) promoter across 15 CpG sites in papillary and follicular thyroid carcinomas (PTC and FTC) compared to benign thyroid lesions, and to contextualize these findings through a review of previous studies on TIMP-3 promoter methylation.

Patients with metastatic colorectal cancer (CRC) presenting defective mismatch repair (dMMR) and/or high index of microsatellite instability (MSI-H) are suitable candidates for immunotherapy with immune checkpoint inhibitors (ICIs), such as pembrolizumab and nivolumab. However, the use of these ICIs as neoadjuvant treatment for non-metastatic and metastatic CRCs with these specific molecular alterations is still controversial. Thus, this systematic review (PROSPERO CRD42021258676) evaluated the benefits, toxicity profile, and clinical outcomes of pembrolizumab and nivolumab as neoadjuvant therapy for CRC with dMMR and/or MSI-H. For this, MEDLINE, Scopus, Cochrane Library, and Science Direct databases were used. Twenty-five case reports and four randomized clinical trials were included, and the main outcomes analyzed were overall survival, progression-free survival, pathological response through RECIST 1.1, and the Eastern Cooperative Oncology Group (ECOG) performance status, respectively. In general, the evaluated studies were well conducted according to the assessment tools, and the evidence suggests that combinations of nivolumab plus ipilimumab were more effective to treat metastatic CRC with dMMR and/or MSI-H than nivolumab alone. Regarding pembrolizumab, clinical evidence demonstrated its safety and efficiency for patients with this subtype of CRC in metastatic and locally advanced stages. This review indicates therapeutic promising potential of ICIs for patients with dMMR and/or MSI-H CRCs. Additionally, alterations in PI3K and JAK pathways are important mechanisms of resistance and represent an opportunity for the development of new drugs. Therefore, molecular investigations should be performed to uncover causes of therapeutic failure.

Aggressive thyroid carcinomas are rare malignancies characterized by a high impact on patient's lives and poor prognosis. The available literature is scarce presenting divergent data concerning the clinical outcomes, prognostic factors and variable mutational signature studies. We aim to collect data from the literature and assemble a systematic review. The literature from 2007 until May 2025 was searched using PubMed. Studies bearing data concerning clinical aspects, prognostic outcomes, or molecular characteristics of differentiated high-grade (DHGTC), poorly differentiated (PDTC), and anaplastic thyroid carcinomas (ATC) were retrieved. Original articles in English, ethically conducted on human patients, were selected. From 688 articles, 39 were included. DHGTC has a good 5-year survival rate (5YSR) of 76%, 23.18% metastasis rate, 42.23%, lymph node involvement (LNI), 61.44% extrathyroidal extension (ETE), majority being diagnosed in stage III. PDTC has an intermediate 5YSR of 65.71%, 21.17% distant metastasis, 32.22% LNI, and 55.19% ETE, majority diagnosed in stage III. ATC has a grim 2-year survival rate of 11.15%, 42.15% metastasis, 44.14%, LNI, and 58.51% ETE, majority presented in stage IV-B. Mutational profiling shows that each carcinoma has its unique set of molecular alterations. Most positive prognostic comes for DHGTC, then PDTC, and finally, ATC.

Recent research suggests a link between KRAS mutations and the effectiveness of ICIs, as KRAS-driven tumors may possess unique immunogenic features that influence the tumor microenvironment. These mutations can increase tumor mutation burden (TMB) and neoantigen load, potentially leading to improved responses to ICIs. This meta-analysis aims to consolidate existing evidence on the impact of KRAS mutations as a predictive factor for survival and treatment outcomes in patients with advanced NSCLC treated with ICIs. A comprehensive search strategy was designed by a biostatistician and pulmonologist, targeting PubMed, Web of Science, and Scopus databases up to May 2022. The outcomes assessed included overall survival (OS) and progression-free survival (PFS), reported as log hazard ratios (HRs) with corresponding standard errors (SEs). A pooled estimate of the HR effect size was calculated using Review Manager (RevMan, Cochrane Collaboration, London, UK). Heterogeneity among studies was evaluated using the Cochran Q test and the I2 statistic. Ultimately, 10 articles were deemed suitable for inclusion in the systematic review from a total of 8722 screened titles and abstracts. The presence of KRAS+ mutations had a significant prognostic factor for better OS in NSCLC patients treated with checkpoint inhibitors (HR = 0.89, 95% CI: 0.79-0.99) and for better PFS in NSCLC patients treated with checkpoint inhibitors (HR = 0.72, 95% CI: 0.59-0.87). In conclusion, our study indicates that KRAS mutations may serve as a potential positive predictive biomarker in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitor monotherapy.

Colorectal cancer (CRC) is a leading cause of oncologic death worldwide. Elucidating the molecular mechanisms that underpin its pathogenesis is essential for identifying novel therapeutic targets. Pseudogenes have historically been regarded as non-functional genomic vestiges but have gained recognition for their contributory roles in the oncogenesis of CRC.

To study the recent advances in Pediatric colorectal cancer (PCRC), including molecular profiling, clinical and genetic characteristics, screening guidelines, and treatment strategies.

Basal cell carcinoma (BCC) is a prevalent form of skin cancer that can be localized or metastatic. Current evidence supports the use of Hedgehog (Hh) pathway inhibitors for locally advanced or metastatic BCC with resistance due to genetic alterations in the Hh pathway. This systematic review evaluated the prevalence of genetic alterations in Hh pathway genes in BCC.

To evaluate the diagnostic accuracy and detection rate of lymph node metastases (LNM) in Papillary Thyroid Carcinoma (PTC) using the One-Step Nucleic Acid Amplification (OSNA) technique compared to conventional pathological methods.

Background: MicroRNAs (miRNAs) in follicular fluid (FF) are being recognized as important regulators of ovarian function and biomarkers of reproductive success. This systematic analysis investigates FF-derived miRNAs and their relationship to polycystic ovarian syndrome (PCOS) and in vitro fertilization (IVF) outcomes. Methods: Following PRISMA recommendations, 21 original papers were included that looked at miRNA expression in FF or granulosa cells from women undergoing IVF, with or without PCOS. The study design, miRNA profiling methodologies, IVF protocols, and clinical results were gathered and analyzed. Results: Across the investigations, 15 miRNAs were regularly implicated, including miR-132, miR-320, miR-222, miR-224, miR-146a, and miR-93. Downregulation of miR-132 and miR-320 was consistently detected in PCOS and associated with decreased steroidogenesis. Elevated miR-222 and miR-146a were linked to insulin resistance and follicular inflammation. In IVF, miR-202-5p and miR-224 were elevated in high-quality embryos and successful cycles, indicating that they have roles in granulosa cell proliferation and estrogen synthesis. MiRNA dysregulation was linked to critical pathways, such as PI3K/AKT, NF-κB, TGF-β, and WNT. Conclusions: Specific FF miRNAs are consistently linked to PCOS pathogenesis and IVF effectiveness. Their use into noninvasive biomarker panels could improve embryonic selection and personalized reproductive care.

The predictive value of tumor mutation burden (TMB) on the efficacy of immunotherapy has been confirmed in multiple cancer types in previous studies. For urothelial carcinoma (UC) patients treated with immune checkpoint inhibitors (ICIs), whether TMB is a suitable biomarker to predict the benefit of ICIs remains a matter of much debate. We conducted this meta-analysis to evaluate the role of TMB in patients with UC treated with ICIs.

Acute lymphoblastic leukemia (ALL) is a prevalent malignant hematologic disease characterized by the abnormal proliferation and accumulation of immature lymphocytes in bone marrow and lymphoid tissues. In our study, Oxford Nanopore Technologies (ONT) sequencing was performed to investigate four types of methylation modifications-6 mA, CHG, CHH, and CpG-in a pair of monozygotic twins, where one twin has ALL and the other is healthy. The results showed the significant global hypomethylation of CpG sites and an increase in 6 mA, CHG, and CHH methylation in the twin diagnosed with ALL. Notably, the hypomethylation of CpG was particularly increased in the open sea, gene body, and 3'UTR regions, while 6 mA and CHG modifications exhibited high methylation levels in the gene body, TSS1500, TSS200, and 3'UTR regions. Additionally, CHH modifications showed high methylation across all genomic regions. Within the differential methylation loci (DML), we identified several genes related to tumorigenesis and progression (such as ZDHHC11, NBPF1, and TPTE). Furthermore, we systemically reviewed the literatures on leukemia and DNA methylation modifications, providing a comprehensive description of their correlation. In summary, these findings indicate that DNA methylation plays a crucial role in the onset and progression of ALL, offering valuable insights for future research into its impact on leukemia development.

Accumulating evidence demonstrates that miRNAs exhibit enhanced diagnostic sensitivity and specificity compared to the conventional hepatocellular carcinoma (HCC) biomarker alpha-fetoprotein (AFP), particularly showing promising clinical utility in early-stage HCC detection. However, insufficient transparency in methodology reporting compromises the validity assessment of these findings and hinders their translational applications. In this study, we investigated the adherence to the STARD criteria in studies investigating the diagnostic accuracy of miRNA for liver cancer. In addition, the quality of reporting was examined to identify factors influencing the quality of reporting.

Lung cancer (LC) is the most incident malignancy and a leading cause of cancer-related fatalities. The lack of dissemination of effective screening tools hinders early detection, resulting in late-stage diagnosis, mostly associated with high mortality. Gene-specific methylation alterations detected in plasma or serum circulation cell-free DNA (ccfDNA) have been investigated as a possible screening tool. Thus, the main aim of this systematic review and meta-analysis was to critically assess published data on the use of ccfDNA methylation-based biomarkers for detection of LC. PubMed, including MEDLINE and Scopus databases, were systematically searched for eligible articles evaluating the diagnostic performance of ccfDNA methylation alterations in that setting. A bivariate random-effect model was employed to calculate pool estimated sensitivity and specificity. Accuracy subgroup analyses, according to histological subtype, stage, and smoker status were carried out. A total of 1961 articles were retrieved, of which 44 met inclusion criteria. The meta-analysis generated a pooled sensitivity of 54% (CI 95% 48-60%) and a pooled specificity of 86% (CI 95% 83-87%) for LC detection. The most frequently tested host-genome methylation markers were RASSF1 A, APC, SHOX2, SOX17, and HOXA9. Overall, methylation analysis of ccfDNA detects LC with high specificity but modest sensitivity. Further research is required to improve diagnostic performance, establish methodological standards and determine whether this might complement existing screening strategies to increase effectiveness. Systematic review registration PROSPERO CRD42023408964.

This systematic review and meta-analysis aimed to compare the survival outcomes and cytogenetic profile of primary acute lymphoblastic leukemia (p-ALL) and secondary ALL (s-ALL), including antecedent-malignancy ALL (am-ALL) and therapy-related ALL (tr-ALL). The search was performed in PubMed/MEDLINE, Scopus, Web of Science, Embase, and ProQuest databases from January 1, 1990, to July 31, 2023, using the keywords "acute lymphoblastic leukemia" and "second cancer" to identify cohort studies that compared p-ALL and s-ALL in terms of survival outcomes and cytogenetic profile. The risk of bias in the included studies was assessed using the Joanna Briggs Institute (JBI) for Cohort Studies. A total of 7 studies involving 13,542 participants were analyzed. The results revealed an HR of 2.35 (95%CI:1.38-4.01) for overall survival (OS) and 2.06 (95%CI:1.05-4.06) for relapse-free survival (RFS). Subgroup analysis of tr-ALL patients showed a significantly higher HR of 3.40 (95%CI:2.32-4.99) for OS in this subgroup. Furthermore, the meta-analysis indicated an OR of 3.45 and 5.90 for mixed lineage rearrangement (MLL) and hypodiploidy, respectively. The study highlights the need for a better understanding of the survival rates and cytogenetic profile of secondary ALL, particularly tr-ALL, and the importance of personalized treatment strategies for this subtype.

Pediatric high-grade glioma of the spinal cord is an exceptionally rare entity with limited understanding of its natural history and biological behaviors, particularly in comparison to similar tumors in adults or within the intracranial compartment. This updated systematic review comprehensively investigates all cases in the English literature through March 2024 following PRISMA guidelines with an emphasis on histopathologic diagnosis, treatment paradigms, outcome, and molecular characterization where reported. Eighty-three articles met inclusion with 132 spinal tumors diagnosed as "glioblastoma" based on relevant histopathologic criteria. Fourteen studies included molecular genetic testing, with IDH status reported in only two patients and seven patients incurring a histone mutation. While a more recent year of treatment, greater extent of resection, and utilization of adjuvant chemoradiation were associated with increased overall survival (OS) to suggest that modern treatment regimens are improving clinical outcomes, insufficient data exists to determine differences in OS based upon molecular profiling thereby limiting therapeutic progress. The authors further include two new cases to juxtapose molecular tumor profiles with potential differences in outcome. This review ultimately aims to emphasize the importance of reporting and utilizing integrated diagnoses to better understand the natural history and prognosis of high-grade glial tumors in the pediatric spine. Challenges in this field continue to include tumor rarity, an inability to reliably update the molecular profiles of previously obtained tissue, and reliance on literature published prior to the "molecular era" of CNS neoplasms, which likely represents a broader spectrum of high-grade genetic variants.

Although numerous Mendelian randomization studies on risk factors have been conducted in male medicine, a systematic synthesis of these findings is still lacking. This review searched relevant literature in PubMed and the Web of Science published before May 2024; systematically summarized the progress in the application of Mendelian randomization in male infertility, erectile dysfunction, prostate cancer, and prostatitis; summarized and classified the risk factors affecting men's health, such as the gut microbiota, modifiable risk factors and related diseases; and presented some problems and solutions that were presented in these studies. This information offers valuable insights into the etiology and pathogenesis of male-specific diseases.

Mutations in Alpha thalassemia/mental retardation X-linked (ATRX) have been implicated in several cancers, including gliomas, sarcomas, neuroendocrine tumors, and other mesenchymal malignancies. ATRX loss contributes to oncogenesis, accelerates tumor growth, and reduces survival by disrupting epigenetic and telomere mechanisms. Additionally, ATRX loss can increase tumor sensitivity to treatment therapies. While research has explored ATRX expression in many cancers, data on its relationship to prognosis in pituitary neuroendocrine tumors (PitNETs) remain inconsistent. This systematic review aims to summarize all available studies on ATRX mutations and expression in PitNETs. A systematic search of PubMed, Scopus, and EMBASE databases was conducted to identify publications between 2014 and 2025 that investigated ATRX mutations or expression in PitNETs, following PRISMA 2020 guidelines. Of 32 identified studies, ten met the inclusion criteria, covering a total of 513 PitNETs. Only 20 tumors (3.9%) showed a loss of ATRX expression. Among these, 60% exhibited corticotrophic pathology, while 20% displayed lactotrophic pathology. A small subset of tumors (30%) was classified as pituitary carcinomas with aggressive and proliferative characteristics. Additionally, 10% demonstrated the alternative lengthening of telomeres (ALT) phenotype, 50% had concurrent TP53 mutations, and 25% had elevated Ki-67 indices, indicating a higher proliferative index. Although ATRX mutations are rare in PitNETs, tumors with ATRX loss tend to be more aggressive and exhibit proliferative and transformative properties. Due to the limited number of cases, further studies with larger, prospective cohorts are needed to better understand the role of ATRX loss in PitNET progression and aggressiveness.

Gastric cancer (GC) represents a prevalent form of malignant neoplasm characterized by elevated incidence and fatality rates, limited early detection capabilities, and unfavorable clinical outcomes. Its occurrence and development involve complex biological processes. As a recently identified form of cellular demise, ferroptosis has been observed across multiple cancer types, garnering significant research interest in contemporary studies. Nevertheless, the precise regulatory networks governing ferroptosis in gastric cancer, along with its functional implications in the initiation and advancement of this malignancy, remain unclear. This study seeks to elucidate the functional significance of ferroptosis in the pathogenesis of GC, systematically review the dysregulated metabolic pathways associated with this cell death process, and elucidate the intricate interactions among ferroptosis-related signaling cascades. These investigations are expected to establish a novel conceptual framework for understanding the molecular pathogenesis of gastric cancer and identifying potential therapeutic interventions. A comprehensive literature search was conducted using PubMed to identify relevant original research articles and review papers examining the molecular mechanisms underlying ferroptosis in gastric carcinoma. The search strategy incorporated the following key terms: "Ferroptosis," "Ferroptosis and gastric cancer," "Ferroptosis and GSH," "Ferroptosis and GPX4," "Ferroptosis and system Xc-," "Iron metabolism," "lipid peroxidation," "FSP1-CoQ10," "DHODH-CoQH2," "GCH1-BH4," "ferroptosis inducer," etc. Emerging evidence from contemporary research indicates that targeted ferroptosis represents a novel and potentially efficacious treatment modality for patients with gastric cancer. Along with the identification of precise molecular targets for therapeutic intervention, the metabolic regulatory networks associated with ferroptosis remains an essential area for future research endeavors.

The prevalence and prognostic value of programmed death ligand 1 (PD-L1) expression, as a potential biomarker in vulvar squamous cell carcinomas (VSCCs), remain underexplored. We searched the PubMed, Scopus, Embase, and Cochrane Library databases until July 2024 for articles examining PD-L1 expression in VSCCs. Random-effects meta-analyses summarized PD-L1 expression overall and in subgroups by immunohistochemistry antibody type, positivity cutoff, tumor stage, and HPV positivity. Additionally, random-effects meta-analyses summarized the association between PD-L1 positivity and cancer prognosis. We included 26 studies comprising 1912 VSCC cases. The summary PD-L1 positivity rate in tumor cells was 59.9% (95% confidence interval [CI]: 47.7-71.4%; I2 = 96%, n = 26), influenced by the different cutoff thresholds utilized to define PD-L1 positivity. Compared to tumor cells, positivity rates were higher in intratumoral immune cells (75.6%; 95%CI: 52.9-92.5; I2 = 95.4%, n = 6) and peritumoral cells (78.9%; 95%CI: 54.4-95.5%; I2 = 91%, n = 3) but with overlapping 95%CIs. No heterogeneity was observed in the rates by tumor stage or HPV status. Positive PD-L1 expression was associated with worse overall (hazard ratio [HR] = 1.43; 95%CI: 1.06-1.93; I2 = 28.9%, n = 7) and progression-free survival (HR = 1.57; 95%CI: 1.07-2.3; I2 = 38.3%, n = 5). The PD-L1 expression rate in VSCC tumor cells varied across studies, was influenced by differences in immunohistochemical evaluation, and was identified as an unfavorable prognostic factor. Large, prospective, multicenter studies with standardized protocols are crucial to further elucidate the clinical significance of PD-L1 expression in VSCCs.

Colorectal cancer is the third most common malignant tumor worldwide and ranks second in terms of mortality. N6-methyladenosine (m6A) modification is the most prevalent internal covalent modification in eukaryotic mRNA and is involved in various stages of RNA processing, including splicing, degradation, and export, playing a crucial role in the onset and progression of many diseases. The m6A modification is co-regulated by methyltransferases, demethylases, and methyl-binding proteins, and it has become a hot topic in cancer research. Based on a systematic review of existing studies on the role of m6A modification in colorectal cancer, this article further expands the research horizon in this field and effectively overcomes the limitations of existing reviews that only focus on discussing a single or a class of methylation regulators.