Ewing family of tumors (EFT) encompass a group of small blue round cell tumors, including Ewing sarcoma (ES) and EWSR1-negative undifferentiated small round cell sarcoma. The distinction between the EFTs is essential from a clinical perspective due to prognostic and therapeutic differences and is substantiated by the advent of molecular testing in the modern era. In this study, we tried to characterize EFTs by using fluorescent in situ hybridization (FISH) and reverse transcriptase polymerase chain reaction (RT-PCR).

Head and neck cancer (HNC), predominantly head and neck squamous cell carcinoma (HNSCC), poses a significant health burden globally. Intensity-modulated radiation therapy (IMRT) has improved outcomes in HNC; however, radiation-induced toxicities, particularly oral mucositis and dermatitis, remain critical concerns. Genetic variations, such as single-nucleotide polymorphisms (SNPs) in the TGF-β1 gene (-509C>T, rs1800469), may modulate these toxicities and impact treatment response.

The emergence of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape of metastatic melanoma. However, despite its success, reliable biomarkers for predicting primary resistance are not available in clinical practice. This study seeks to identify predictors of primary resistance based on novel gene expression signatures. The transcriptomic profile of the tumor microenvironment was analyzed using tissue samples from 46 metastatic cutaneous melanoma patients collected prior to the initiation of ICIs therapy. A primary resistance predictive model was trained with the Discovery FFPE RNA-seq subcohort and validated using an independent external cohort of 54 samples. Additionally, liquid biopsy samples from peripheral blood mononuclear cells were analyzed in 8 patients using single-cell RNA sequencing (scRNA-seq) and in 46 patients using flow cytometry. We identified an 82-gene transcriptomic signature composed of tumor- and immune-related genes that stratifies metastatic cutaneous melanoma patients based on primary resistance to ICIs, with key markers including CXCL13, WDR63, MZB1, FDCSP, IGKC and GRIK3. This signature achieved an AUC of 0.814. Immune deconvolution guided by scRNA-seq revealed four immune cell subsets (Plasma cells, Pre-B cells, memory CD4⁺ T cells, and naive CD4⁺ T cells) as prognostic indicators of resistance. We propose a transcriptomic biomarker signature that accurately predicts primary resistance to ICIs in metastatic cutaneous melanoma. Through the integration of immune deconvolution with circulating immune cell profiles, we derived an ImmuneSignature linked to patient survival. By combining these approaches, we provide a framework for enhancing the prediction of immunotherapy outcomes and offer a novel strategy for identifying therapeutic targets to overcome resistance.

Uterine leiomyosarcoma (uLMS) is a rare but aggressive malignant mesenchymal tumor, accounting for 2-5% of uterine malignancies. Because its symptoms and imaging features often resemble those of benign uterine leiomyoma (LM), accurate preoperative diagnosis remain difficult. This review summarizes recent advances in liquid biopsy for uLMS and explores its potential for early detection, molecular characterization, and treatment monitoring.

Acromegaly is a rare endocrine disorder characterized by the excessive production of growth hormone (GH) in adulthood, usually (95 percent of the time) due to a benign tumor in the pituitary gland (PitNET). Although GNAS variants are the most prevalent cause of sporadic somatotroph tumors, these can rarely occur in a familial setting (5 percent). Hereditary GH-secreting PitNETs can manifest as isolated tumors, such as in familial isolated pituitary adenoma (FIPA) including cases with AIP variants or GPR101 microduplications, (X- linked acrogigantism) or can be part of syndromes like multiple endocrine neoplasia type 1 or type 4, McCune-Albright syndrome, Carney complex or phaeochromocytoma/paraganglioma-pituitary adenoma association. Identifying genetic defects allows an early detection and prompt intervention, essential for preventing complications and improving the quality of life in affected individuals, as well as finding affected relatives before the clinical manifestations of the disease.

Combination immunotherapies such as atezolizumab plus bevacizumab (Atez/Bev) and durvalumab plus tremelimumab (Dur/Tre) improve outcomes in advanced hepatocellular carcinoma (HCC), yet systemic immune mechanisms underlying response remain incompletely defined.

Chimeric antigen receptor (CAR) T-cell therapy has demonstrated safety and modest efficacy against diffuse midline gliomas (DMGs), a highly aggressive pediatric brain tumor. However, mechanisms of CAR T-cell resistance in DMG settings remain unknown.

This study explores the locations and distribution of mutations in the exons of the TP53 gene in pulmonary large cell neuroendocrine carcinomas (LCNEC) and the corresponding expression of p53 as well as the Ki-67 proliferation index. Real-world data from routine diagnostics were collected retrospectively from 149 consecutive cases of pulmonary LCNEC. They included next-generation sequencing (NGS) of the TP53 gene along with evaluation of p53 and Ki-67 expression with immunohistochemistry (IHC). Abnormal p53 expression was defined as strong positive nuclear reaction in more than 20% of the tumor cells or complete absence of immunostaining in tumor cells. Both p53 expression and Ki-67 proliferation index correlated with TP53 mutations. In addition, a statistically significant increase in Ki-67 expression was found for cases with abnormal staining of p53 compared to samples with normal staining. We found that IHC staining for p53 can identify TP53 mutations in pulmonary LCNEC with an overall concordance of 76.6%. Moreover, both pathological patterns of p53 immunostaining and NGS-detected TP53 mutations were associated with higher Ki-67 proliferation indices.

Triple-negative breast cancer (TNBC) is known for its more aggressive clinical behavior, poor prognosis, and distinctive patterns of metastasis. Neoadjuvant chemotherapy (NAC) can influence both tumor cells and the tumor microenvironment. Emerging evidence highlights the critical role of actin cytoskeletal dynamics in cancer progression.

Deficient DNA mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status, which sensitizes tumors to immune checkpoint inhibitors (ICIs), is three times more common with upper tract urothelial carcinoma (UTUC) than with bladder cancer. However, data on ICI efficacy against dMMR/MSI-H advanced UTUC remain limited.

Advanced esophageal squamous cell carcinoma (ESCC) has a poor prognosis, and current treatments provide limited survival benefits. This study aimed to identify prognostic biomarkers and therapeutic targets by genomic profiling of advanced ESCC using circulating tumor DNA (ctDNA).

Anaplastic lymphoma kinase (ALK) is an established therapeutic target in non-small cell lung cancer (NSCLC), predominantly identified in adenocarcinomas. However, ALK rearrangements also occur in de novo squamous and adenosquamous NSCLCs and their clinicogenomic features remain poorly defined.

The RAS signaling pathway is a fundamental regulator of cellular growth, proliferation, and survival. Dysregulation of this pathway is strongly implicated in cancer development, yet systematic strategies for identifying which pathway proteins represent the most promising therapeutic targets remain limited. The rationale of this study was to investigate the diversity of central proteins within the RAS signaling pathway and assess their functional significance in cancer biology. To achieve this, we modeled the human protein-protein interaction network as a metric space using a graph-theoretical framework. Shortest-path distances were computed to identify the most central proteins, which were then classified into functional zones. Proteins located in zone 1, representing the most connected zone, were cross-referenced with curated RAS pathway datasets. Functional enrichment analysis, oncogene/tumor suppressor evaluation, and cancer genome data integration were used to interpret biological roles and therapeutic potential. The results revealed that 95.2% of central RAS proteins are involved in signaling, with 59.5% classified as essential. Key proteins such as BCL2L1, RAF1, RHOA, MAP2K1, EGFR, CDC42, and ANGPT1 were identified as central players in processes including apoptosis resistance, metastasis, angiogenesis, and tumor progression. Several of these proteins also showed strong associations with established oncogenes and successful therapeutic targets. In conclusion, this study demonstrates that central proteins in the RAS signaling pathway exhibit functional diversity that underpins their importance in cancer progression. These findings provide a reproducible network-based workflow for identifying pathway-relevant molecular candidates and contribute to the development of more precise, pathway-oriented cancer therapies.

This graphical abstract presents findings from a simulation study examining the impact of within-patient correlation on statistical inference in analyses of repeated binary clinical outcomes. Under conditions of strong intracluster correlation (200 patients, 10 observations per patient, 1000 simulated data sets), naive logistic regression that assumed independence substantially underestimated standard errors and led to marked inflation of the type I error rate (30.5%). In contrast, generalized estimating equations (GEE), which appropriately account for within-patient clustering, preserved nominal error control (5.7%). These results underscore the importance of using correlation-adjusted analytic approaches to ensure valid inference when evaluating patient-level exposures in longitudinal or clustered oncology data.

In this study, we assess the activation of autophagy and its impact on cytotoxicity following [HuArgI (Co)-PEG5000]-induced arginine deprivation in AML cells. We have previously shown that arginine deprivation is selectively cytotoxic to AML cells and that cell death is caspase independent and non-apoptotic, hence the mechanism of cell death remained elusive. We tested a panel of 7 AML cell lines, and we first demonstrated that the cytotoxicity of [HuArgI (Co)-PEG5000] to AML cells is long-term and sustained despite re-expression of overexpression of ASS1 in all cell lines. We also demonstrated that arginine deprivation leads to a prolonged and extensive activation of autophagy starting at 24 and lasting up to 120 h in all cells. Autophagy was shown to induce cell death since its inhibition using chloroquine (CQ) significantly decreased [HuArgI (Co)-PEG5000]-induced cytotoxicity, indicating autophagic cell death in AML cells following arginine deprivation. Moreover, we showed that arginine deprivation leads to ROS accumulation and that neutralizing ROS using N-acetylcysteine (NAC) does not affect the autophagic response but completely reverses the cytotoxicity of arginine deprivation, demonstrating that death by autophagy is dependent on ROS generation in AML cells.

Bladder cancer (BC), a leading urogenital malignancy with high mortality, lacks effective early biomarkers. Connexin 43 (Cx43), encoded by GJA1, regulates tumor growth via protein interactions and phosphorylation. While dysregulated in BC, Cx43's downstream regulatory pathways remain unclear. Elucidating these mechanisms is crucial for identifying novel biomarkers and therapeutic targets. qRT-PCR measured Cx43 expression in bladder cancer tissues and cells. Kaplan-Meier analysis assessed correlation between Cx43 expression and patient overall survival (OS) and progression-free survival (PFS). Using MTT, colony formation, and Transwell assays, we evaluated how silencing Cx43 affects BC cell proliferation, migration, and invasion in vitro. Protein-protein interaction (PPI) analysis predicted potential Cx43 downstream targets. Co-immunoprecipitation (Co-IP) confirmed specific interaction between Cx43 and c-Src proteins. Western blotting (WB) examined effects of Cx43 knockdown on expression of these predicted downstream targets. Finally, in vivo mouse xenografts validated Cx43's role in BC cell tumorigenesis. Cx43 was upregulated in bladder cancer tissues and its elevated expression correlated with poor patient prognosis. Silencing Cx43 significantly suppressed BC cell proliferation, migration, and invasion. Functional rescue experiments implicated the c-Src/PTEN pathway in mediating the oncogenic effects of Cx43. Mechanistically, Cx43 drives BC progression by facilitating c-Src-mediated suppression of the tumor suppressor PTEN and subsequent activation of FAK signaling. This study unveiled a novel regulatory pathway, Cx43 promotes malignant bladder cancer progression by modulating the c-Src/PTEN/p-FAK axis.

Extramedullary leukaemia, also known as myeloid sarcoma, is a rare manifestation of acute myeloid leukaemia (AML) that typically occurs in conjunction with bone marrow involvement. It is characterized by infiltration of leukemic cells into extramedullary tissues, including the skin, soft tissues, and lymph nodes, where it may present as mass-like or nodular lesions. When associated with high-risk cytogenetic abnormalities, extramedullary disease may exhibit particularly aggressive behaviour and pose substantial diagnostic challenges, especially when it precedes or masks systemic manifestations of AML.

Current biomarkers of epithelial ovarian cancer (EOC) lack the required sensitivity and specificity for early detection. MicroRNAs (miRNAs) are implicated in cancer progression, and their serum expression could serve as a non-invasive diagnostic tool. This study focuses on evaluating the expression of serum miR-200a, miR-200b, and miR-200c and their association with clinico-pathological characteristics in EOC patients.

Hepatocellular carcinoma (HCC) is a prevalent and highly aggressive cancer, characterized by elevated morbidity and mortality. Ubiquitin-conjugating enzyme E2 (UBE2) plays a crucial role in regulating HCC development, although the underlying mechanisms remain poorly understood.

MET alterations, including MET fusions and splicing variants (F/SVs), are linked to glioma progression, but the clinical features remain underexplored since the 2021 WHO classification of tumors of the CNS. We aimed to systematically depict the MET F/SVs and patient characteristics in a multicenter cohort focusing on clinical, pathological, and survival features. We studied data from 1,041 patients with MET F/SVs data from the public Chinese Glioma Genome Atlas database and the TruSight Tumor 170 study. Clinical outcomes were evaluated based on the RANO criteria. We used chi-square and Fisher's exact tests for variable analysis. Kaplan-Meier analysis was used to assess survival trends, while univariate and multivariate analyses revealed the prognostic value of MET F/SVs. Immunohistochemical staining was performed to demonstrate the MET expression level. Among the 1,041 patients, 49 patients had F/SVs (4.70%), and 23 had ZM fusion (PTPRZ1-MET fusion gene; 2.21%). Among the 67 recurrent grade 4 astrocytomas, the proportions of F/SVs (11.94%, n = 8) and ZMs (5.97%, n = 4) were the highest. MET F/SVs were significantly associated with malignant clinical outcomes in the IDH-mutant astrocytoma cohort, with a frequency of 5.04% (18/357) across all WHO grades. Multivariate analysis revealed that the MET F/SVs were independently associated with worse survival in astrocytoma patients [overall survival (OS): p = 0.0011; progression-free survival (PFS): p = 0.004]. ZM fusion was associated with a worse prognosis in both astrocytoma (OS p < 0.001, PFS p < 0.001) and glioblastoma (OS, p = 0.252; PFS, p = 0.010) patients. We highlight the utmost relevance of ZM fusion as an adverse prognostic factor in astrocytoma (11/382, 2.88%) and glioblastoma grade 4 (11/401, 2.74%) patients and suggest that the grading of these tumors should be refined.