Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality, characterized by a poor prognosis. The advent of immunotherapy has significantly altered the treatment landscape for NSCLC. CD8+ T cells, key mediators of immune responses, play a pivotal role in the prognosis and progression of the disease. This study aims to develop a CD8+ T-cell-related prognostic model to enable more precise prognostic evaluations and enhance clinical decision-making in immunotherapy for patients with NSCLC.

Forkhead box M1 (FOXM1), a critical transcription factor, is implicated in tumorigenesis by regulating cell cycle progression, proliferation, and metastasis. Similarly, Ubiquitin-conjugating enzyme 2C (UBE2C), a key component of the ubiquitin-proteasome system, plays a pivotal role in mitotic progression and genomic stability. Aberrant overexpression of FOXM1 and UBE2C has been reported in various malignancies; however, their functional interplay in NSCLC remains poorly understood. In this study, we investigated the oncogenic roles of FOXM1 and UBE2C in NSCLC through in vitro and in vivo models, as well as clinical specimen analysis. Our findings demonstrate that FOXM1 transcriptionally upregulates UBE2C, thereby promoting NSCLC cell proliferation, invasion, and tumor progression via activation of oncogenic signaling pathways. Mechanistically, FAM64A stabilized FOXM1 expression, contributing to its pro-tumorigenic effects on NSCLC progression. Furthermore, FOXM1/UBE2C axis disruption impairs tumor growth, highlighting its potential as a novel therapeutic target. This study provides new insights into the molecular mechanisms underlying NSCLC pathogenesis and suggests that targeting the FAM64A/FOXM1/UBE2C axis may offer an effective strategy for NSCLC treatment.

Brain metastases reduce overall survival rates of patients with non-small cell lung cancer (NSCLC); patients with epidermal growth factor receptor 2 (ERBB2 [formerly HER2])-mutant NSCLC are more likely to have baseline brain metastases. Trastuzumab deruxtecan (T-DXd) is an approved ERBB2-directed treatment for previously treated unresectable or metastatic ERBB2-mutant NSCLC.

Breast cancer (BC) is the most frequently diagnosed cancer type and the leading cause of cancer-related mortality among females worldwide. This study aimed to investigate the role of RPL17 in BC. Our findings revealed that the expression of RPL17 in BC tissues and cell lines was significantly elevated compared to normal tissues and cells. The knockout of RPL17 in BC cell lines profoundly inhibited their proliferation, migration, invasion, and cell adhesion abilities. Furthermore, RPL17 knockout (RPL17-KO) cells exhibited increased apoptosis. Mechanistically, RPL17-KO cells demonstrated decreased MAPK signaling. Finally, the overexpression of RPL17 promoted the epithelial-mesenchymal transition (EMT) process in BC cells. RPL17-overexpressing cells displayed enhanced proliferation, migration, invasion, and cell adhesion abilities, alongside reduced apoptosis and increased MAPK signaling. Collectively, this study suggests that RPL17 functions as an important oncogene and may represent a potential therapeutic target for BC.

Multiple endocrine neoplasia type 5 (MEN5) is an emerging syndrome caused by germline pathogenic variants involving the MYC Associated Factor X (MAX) gene. Affected individuals typically have pheochromocytomas, often bilateral, at a relatively early age. In MAX pheochromocytoma cohorts, pituitary adenomas are rarely reported. The role of MAX as a tumor suppressor gene in the pituitary gland has not been directly proven to date.

The therapeutic landscape of advanced urothelial carcinoma (UC) is evolving, making the prediction of immune checkpoint inhibitor (ICI) therapy efficacy crucial. Standalone biomarkers offer limited predictive value, necessitating integrative approaches combining clinicopathological, laboratory, and molecular factors to enhance accuracy. This study aimed to evaluate clinical and molecular factors, including the real-life performance of PD-L1 IHC, to improve treatment outcome prediction in ICI-treated UC patients, ultimately developing a more precise therapy selection model.

Matrix stiffness is a defining feature of pancreatic ductal adenocarcinoma (PDAC) and drives malignant progression through mechanisms that remain poorly understood. Using an ensemble machine learning approach, we integrated multiomics data from 886 patients with mechano-biology models to develop a nine-gene matrix stiffness-associated gene signature (MSAGS). MSAGS demonstrated superior prognostic accuracy in independent cohorts, outperforming 87 existing signatures. We identified SLC20A1 within MSAGS as a novel mechano-immunological checkpoint where matrix stiffness activates an SLC20A1-STAT3 positive feedback loop, driving dual immunosuppression via TGF-β1-mediated CD8+ T-cell exclusion and PD-L1-induced T-cell dysfunction. Importantly, targeting SLC20A1 synergized with anti-PD-L1/TGF-beta bispecific antibody (BiTP, Y101D), enhancing tumor suppression and extending survival in orthotopic PDAC models by increasing the infiltration and function of cytotoxic CD8+ T cells. This work establishes MSAGS as a clinically translatable prognostic tool and positions SLC20A1 targeting as a transformative strategy to overcome PDAC immunotherapy resistance, thereby repositioning matrix stiffness as a druggable target.

Glioblastoma (GBM) is the most malignant and highly recurrent brain tumor. Although over half of the GBM patients are elderly patients, the understanding of how aging affects GBM progression remains limited.

Molecular subtyping is fundamental in cancer research and clinical management of cancer, guiding treatment planning, monitoring therapeutic response, and informing prognosis. Early methods were designed specifically for gene expression data due to the lack of other molecular data types. Thanks to breakthroughs in high-throughput technologies, recent subtyping tools have shifted their focus to integrating multi-omics profiles to uncover novel subtypes that better reflect genetic variation, molecular pathogenesis, tumor heterogeneity, and host response biological mechanisms. However, these integrative approaches have not been able to fully exploit the complementary potentials of diverse molecular data types. They often rely on specific omics types with large common sample size and fail to incorporate important biological knowledge in their models. Here, we introduce Disease subtyping using Spectral clustering and Community detection from Consensus networks (DSCC), a method designed to identify meaningful disease subtypes from a wide range of molecular data, including gene expression, miRNA expression, DNA methylation, copy number variation, somatic mutations, protein abundance, and metabolite levels. We demonstrate the superiority of DSCC over state-of-the-art cancer subtyping methods using 43 cancer datasets with more than 11,000 patients. Furthermore, the incorporation of DSCC-derived subtype information as a covariate in prognostic models improves survival prediction accuracy and robustness. The DSCC source code, data, and scripts for reproducing all results in this study are available at https://github.com/tinnlab/DSCC.

The two-sample Mendelian randomization approach was used to assess the potential causal relationships between 33 oral microbes and salivary gland cancer.

To develop a manual "centrifuged-enhanced cytosmear" technique for cytologic and immunohistochemical analysis of hypocellular vitreous biopsy specimens in vitreoretinal lymphoma (VRL).

Mitochondria, as the center of cellular energy metabolism, play multiple key roles in the progression of triple-negative breast cancer (TNBC). Mitochondrial fission regulator 1 (MTFR1) is a mitochondrial regulatory factor that plays a part in regulating mitochondrial fission and cell development. It is still unknown how MTFR1 functions in TNBC. We discovered MTFR1 to be a crucial gene in TNBC with clinical diagnostic value using database mining analysis. The effects of MTFR1 on TNBC cell proliferation, migration, invasion, and mitochondrial function were determined using the Cell Counting Kit-8, wound healing, and Transwell assays. Nude mouse models were established to explore the impact of MTFR1 on TNBC tumor growth and metastasis. Additionally, western blot and transcriptome sequencing (RNA-seq) were used to investigate the mechanism of MTFR1's involvement in TNBC progression. We used database extraction, WGCNA, Cox regression, and ROC (receiver operating characteristic) curve analysis to identify and confirm MTFR1 as a critical gene in TNBC. In TNBC patients, high MTFR1 expression is related to poor prognosis and diagnostic value. Knockdown of MTFR1 inhibits the proliferation and metastasis of TNBC cells and tumor bodies, affecting mitochondrial function. MTFR1 knockdown inhibits the growth, metastasis, and mitochondrial function of TNBC cells and tumors. Furthermore, transcriptome sequencing and western blot experiments confirmed that MTFR1 knockdown inhibits the activation of the NF-κB signaling pathway. In this study, we report for the first time that MTFR1 is a critical gene upregulated in TNBC. MTFR1 is an oncogene in TNBC and is involved in cell growth, migration, and mitochondrial function, and promotes TNBC progression through the NF-κB signaling pathway. Therefore, targeting MTFR1 may be a promising therapeutic target for TNBC patients.

Macrophage polarization engenders an immunosuppressive microenvironment, thereby facilitating the survival and epithelial-mesenchymal transition (EMT)-like changes of malignant plasma cells. Ubiquitin (Ub), a short polypeptide predominantly involved in proteasome-mediated protein degradation, has been detected extracellularly in body fluids. In certain diseases, it exerts immune-regulatory functions, including the modulation of macrophage polarization. Nevertheless, its immune-regulatory role in multiple myeloma (MM) remains undetermined. This study investigated the role of extracellular ubiquitin (eUb) in macrophage polarization and MM progression. We demonstrated that serum eUb levels were significantly higher in MM patients than in healthy volunteers. Elevated eUb levels were closely associated with a poor prognosis in MM patients. Exposure to eUb induced M2 macrophage polarization, which in turn promoted MM cell proliferation and EMT via the CXCR4/JAK1/STAT3 pathway. Notably, STAT3 was identified as a transcription factor that directly binds to the CXCR4 promoter, enhancing its expression and establishing a positive-feedback loop. Collectively, eUb promotes MM cell proliferation and EMT-like changes by driving M2 macrophage polarization through activation of the CXCR4/JAK1/STAT3 positive-feedback pathway. These findings underscore the pathological significance of eUb in the MM tumor microenvironment and suggest that targeting this pathway may provide novel therapeutic strategies for MM.

Bone morphogenetic protein-9 (BMP9) has been implicated as a regulator of metastasis and tumor angiogenesis, with contrasting studies demonstrating both pro- and antiangiogenic roles for BMP9 across different cancer cell lines and animal models. However, these works have yet to define the contribution of the type-II BMP receptor (BMPR-II) to these processes, or assess whether the effects of BMP9 are mediated via actions on the endothelium, the tumor, or its microenvironment. Here, we demonstrate that the heterozygous (Bmpr2EC+/-) or homozygous (Bmpr2EC-/-) deletion of BMPR-II in the pulmonary endothelium is associated with increased overall burden and vascularization of metastases in the lungs of mice subjected to the EO771 orthotopic engraftment model of metastatic breast cancer. These increases, relative to Bmpr2EC+/+ littermates, were observed despite equivalent primary mammary tumor growth across mice of all genotypes. In vitro, secreted factors or extracellular matrix components from BMPR-II-silenced human pulmonary arterial endothelial cells (HPAECs) did not alter EO771 proliferation relative to controls. However, endothelial BMPR-II depletion did eliminate the capacity of BMP9 to suppress both HPAEC migration to VEGF165 and EO771 transmigration across an HPAEC monolayer. In a tail vein injection model, the short-term establishment of EO771 cell metastatic lesions was equivalent in the lungs of female Bmpr2EC+/- and Bmpr2EC-/- mice, relative to Bmpr2EC+/+ controls, suggesting that the enhanced lung tumor burden observed in orthotopically implanted mice with endothelial Bmpr2 deletion is likely a consequence of enhanced tumor vascularization, rather than altered lung retention and engraftment. Our findings identify an important role for endothelial BMPR-II signaling in regulating the vascularization of metastatic lesions in the lungs.

Circulating tumor DNA (ctDNA) provides a noninvasive method to clarify patients' genomic alterations. This study evaluated plasma-derived ctDNA before second-line osimertinib administration to explore the relationships between genomic alterations and clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC).

FGL1 (fibrinogen-like protein 1) is considered to be closely related to cell proliferation and differentiation. The purpose of this study was to explore the value and mechanism of FGL1 as a prognostic indicator for gastric cancer (GC).

Germline predisposition (GP) is associated with a variety of hematolymphoid malignancies. While GP has been addressed mostly in myeloid malignancies, recent diagnostic systems have newly introduced GP in lymphoid malignancies; however, evidence and data are limited, particularly in pediatric patients. In this study, we investigated the frequency and characteristics of GP in pediatric lymphoid malignancies.

The study aimed to investigate the characteristics of CEBPA mutations in Chinese acute myeloid leukemia (AML) patients.

The goal was to investigate the clinical features and diagnostic methods of children with t(8;21)/ AML1-ETO positive acute myeloid leukemia with basophilic granulocytosis.

By integrating whole-genome resequencing (WGR) with longitudinal transcriptomic profiling, this study aimed to unravel the genetic-transcriptional regulatory network underlying thyroid immune-related adverse events (irAEs) in non-small cell lung cancer (NSCLC) patients treated with sintilimab. A key objective was to identify molecular biomarkers with predictive and therapeutic relevance.