Lactate metabolism is a hallmark of cancer metabolic reprogramming, shaping tumor immunity and therapeutic resistance, yet clinically accessible and low-cost methods to assess intratumoral lactate activity remain limited.

Esophageal squamous cell carcinoma (ESCC) shows considerable variation in incidence across different regions and is affected by various risk factors, including smoking and HPV infection. This article presents a rare case of ESCC that metastasized to the anal region, illustrating the effectiveness of whole-exome sequencing and clonal evolution analysis in identifying the origins of the metastasis. The findings reveal distinct clonal characteristics between the primary tumor and the metastatic site. This underscores the importance of molecular profiling for developing effective treatment strategies.

Macrophage-related genes (MRGs), a group of pivotal regulators governing macrophage differentiation, polarization, and function, have increasingly been recognized as critical modulators in tumor progression and immune evasion. However, the molecular expression profiles of MRGs and their intricate relationships with the immune microenvironment in breast cancer (BRCA) remain insufficiently investigated.

Esophageal squamous cell carcinoma (ESCC) is a cancer that is common worldwide. Its morbidity and mortality rates remain high, seriously threatening human health. In the tumor microenvironment (TME), CD8+ T cells undergo a series of dynamic changes that have important implications for tumor progression and the efficacy of immunotherapy. Our research aims to construct novel molecular subtypes through the gene expression profiling of CD8+ T cells during differentiation and to predict the prognostic and therapeutic effects in ESCC patients.

C-terminal binding protein 1 (CTBP1) is an NAD(H)-dependent transcriptional corepressor that links cellular metabolic state to chromatin-based gene regulation. Since its initial identification, CTBP1 has been implicated in a broad range of developmental and pathological processes, including cancer. Increasing evidence suggests that CTBP1 integrates redox cues, epigenetic repression, and transcriptional networks controlling epithelial plasticity, survival, DNA damage responses, and therapy resistance across multiple malignancies. In this review, we critically examine the current literature on CTBP1 structure, regulation, and function, with a particular focus on cancer biology. We synthesize findings from experimental studies that support CTBP1 as an oncogenic driver in specific tumor contexts, while explicitly highlighting settings in which evidence remains indirect, incomplete, or confined to locus-associated noncoding RNAs rather than CTBP1 protein itself. We further discuss the constraints and uncertainties surrounding CTBP1-directed therapeutic strategies, including incomplete mechanistic validation, context-dependent functions, and potential on-target toxicity arising from CTBP1's roles in normal metabolic and transcriptional homeostasis. Overall, this review positions CTBP1 as a context-dependent transcriptional integrator whose pathological functions are shaped by metabolic stress and epigenetic regulation, while emphasizing unresolved questions and experimental gaps that must be addressed before CTBP1 can be reliably evaluated as a therapeutic target.

Spatial transcriptomics technologies such as Xenium, MERFISH, and Visium HD enable high-resolution profiling of gene expression while preserving tissue architecture. However, most computational methods for spatial analysis do not explicitly model local tissue context, such as boundaries, neighborhoods, or gradients. Here, we present SpNeigh (https://github.com/jinming-cheng/SpNeigh/), an R package for spatial neighborhood analysis and spatially aware differential expression modeling. SpNeigh includes tools for boundary detection, spatial neighborhood extraction, distance-based weighting, and gradient-based statistical testing. It supports both region-based differential expression and smooth spatial modeling using spline-based regression, along with a spatial enrichment index that identifies genes enriched near defined spatial features. We demonstrate the utility of SpNeigh across multiple platforms and tissues, including mouse brain, human breast cancer, and human liver, revealing intermediate populations at tissue interfaces, immune microenvironment differences, and spatially zonated gene expression patterns. SpNeigh offers a flexible and interpretable framework for dissecting spatial gene expression dynamics in complex tissues.

The transcription factor c-MYC (MYC) is deregulated in ~70% of human cancers. Through de novo motif discovery analysis on published MYC ChIP-seq datasets from cancer cell lines, we found cell-type-specific co-enrichment of the TRE motifs (AP-1 binding sites) alongside MYC's canonical EBOX motif. MYC binds indirectly to TRE motifs in cooperation with AP-1 transcription factors, and these indirect interactions occur predominantly at enhancers rather than promoters. At elevated MYC levels, as seen in cancers, MYC's indirect binding to TRE sites at enhancers increases. Integration of ChIP-seq and RNA sequencing data revealed that TRE enhancer-binding sites are frequently associated with MYC-mediated transcriptional repression. Gene Ontology analysis showed that MYC utilizes TRE sites to transcriptionally rewire cells, modulating cancer hallmarks like proliferation, apoptosis, and cell adhesion. These molecular insights into how increased MYC levels alter gene regulation could inform new therapeutic strategies targeting cancer-specific MYC functions and its co-regulators.

Lung adenocarcinoma (LUAD) is a leading cause of cancer mortality, necessitating the identification of robust biomarkers and a deeper understanding of its molecular underpinnings. This study is aimed at screening for potential LUAD biomarkers and characterizing their biological functions. Using an integrative computational framework, we combined multitranscriptomic data analysis with three machine learning algorithms (LASSO, SVM-RFE, and random forest) to identify a consensus seven-gene signature (TTC13, TAF1D, ZNF587, PRPF3, LINC01355, TARBP1, and CCNL2). A classifier based on this signature achieved exceptional diagnostic accuracy (AUC = 0.972), with TAF1D identified as the most influential predictor via SHAP analysis. TAF1D was significantly upregulated in tumors, correlated with an immunosuppressive microenvironment, and promoted cancer cell proliferation by regulating cell cycle and immune-related pathways. Critically, TAF1D exhibited significant spatial heterogeneity in expression across different samples and tissue regions, suggesting it may exert region-specific biological functions within the tumor. In conclusion, our work defines a validated gene signature for LUAD, nominating TAF1D as a key oncogenic driver and promising candidate for diagnostic and therapeutic development.

Melanoma represents the most malignant type of skin cancer. It is estimated that approximately 100,000 new cases of melanoma were diagnosed in 2022, resulting in over 7600 deaths in the United States alone. Recently, anticancer peptides (ACPs) have emerged as novel therapeutic agents for cancer, offering higher potency, biocompatibility, and fewer adverse reactions in host cells. One of the druggable targets of melanoma is the melanoma inhibitor of apoptosis (ML-IAP), conventionally inhibited by the nonapeptide AVPIAQKSE. The current study is aimed at enhancing both the binding affinity and safety profile of this peptide through in silico peptide engineering.

Radiotherapy resistance limits colorectal cancer (CRC) treatment efficacy, with only 15%-20% of patients achieving a complete response. Validated biomarkers predicting treatment response and serving as therapeutic targets are critically needed.

Glioblastoma (GBM) is the most prevalent primary brain tumor. Despite extensive investigations, GBM's resistance to the first-line drug temozolomide (TMZ) remains a major challenge in clinical management. This study explores the molecular mechanisms underlying TMZ resistance in GBM, emphasizing the roles of DNA repair gene polymorphisms and intratumoral genetic heterogeneity.

Sarcomatoid urothelial carcinoma (sUC) is associated with poor clinical outcomes. Herein, we evaluated clinicopathologic features (including PD-L1 expression) for institutional cases.

The luminal androgen receptor (LAR) subtype of triple-negative breast cancer (TNBC) differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response. This study aimed to define the molecular basis of the LAR subtype and identify actionable therapeutic targets.

Accurate detection of PIK3CA mutations is essential for guiding PI3K-targeted therapies in breast cancer, yet sequencing is not universally accessible, and single-modality prediction models have limited performance. This study developed a multimodal deep learning framework integrating whole-slide imaging (WSI) and structured clinical data to improve mutation prediction.

The high mortality of pancreatic ductal adenocarcinoma (PDAC) underscores the need for novel treatments. We investigated the potential role of human biofield therapy (BT) in modifying tumorigenic processes in murine and human PDAC cells through a series of in vitro and in vivo studies.

Molecular genetic profiling is crucial for treatment choice in patients with advanced non-small cell lung cancer (NSCLC). The Lung-ONE study aimed to determine the clinical utility of comprehensive genomic profile (CGP) tests, such as FoundationOne CDx or FoundationOne Liquid, in guiding second line therapy decisions for advanced NSCLC patients in Spain. Additionally, the study sought to describe the genomic alterations found in these patients.

Tumour metabolic modulation represents a promising adjuvant therapeutic strategy for cancers, including colorectal cancer (CRC). Dapagliflozin, a clinically approved sodium‒glucose cotransporter 2 (SLC5A2/SGLT2) inhibitor, has attracted considerable attention, yet its functional role in CRC remains unclear. Here, we investigated the oncogenic effect of SLC5A2 on the colorectal mucosal epithelium using transgenic rats and an azoxymethane/dextran sulphate sodium (AOM/DSS)-induced tumour model. Multiple immunofluorescence and tissue microarray analyses of clinical samples revealed an inverse correlation between SLC5A2 expression and natural killer (NK) cell infiltration, highlighting the therapeutic potential of dapagliflozin for CRC treatment. Mechanistically, gene expression profiling analysis and coculture experiments demonstrated that SLC5A2 impairs NKG2D-mediated NK cell cytotoxicity. Furthermore, perforated patch‒clamp and calcium imaging revealed that SLC5A2 modulates the membrane potential and calcium influx, enhancing MHC-I-associated MICA/B secretion via extracellular vesicle (EV) formation and thereby enabling CRC cells to evade NK cell surveillance. Our findings reveal a critical oncogenic role of SLC5A2 in CRC progression and suggest dapagliflozin as a novel therapeutic option, particularly for CRC patients with metabolic comorbidities.

Hepatocellular carcinoma (HCC) remains a major challenge due to its aggressive features, therapeutic resistance, and disease recurrence. Patients with HCC often show anxiety and depression, and mental illness lasts throughout the therapeutic period, exacerbated by treatments such as radiofrequency ablation therapy and liver resection. Exploring novel pathological mechanisms paves the way for the development of HCC treatment with the mitigation of psychiatric issues. Tripartite motif-containing 13 (TRIM13), an E3 ubiquitin ligase, plays a role in central nervous system (CNS) homeostasis and acts as a tumor suppressor in lung and renal cancers. However, its role in HCC is undefined, making it a potentially intriguing target. Here, we demonstrate that TRIM13 expression is significantly downregulated in human HCC Hep3B and HepG2 cells. Adenovirus vector-mediated TRIM13 transgene overexpression (TRIM13 OE) suppresses the viability, proliferation, migration, and invasion of Hep3B and HepG2 cells. TRIM13 OE in the two HCC cell lines increases the levels of apoptosis markers, such as BAX and CASPASE 3, while reducing BCL-2 levels. Additionally, TRIM13 OE cells enhance autophagy by upregulating LC3-I, LC3-II, and BECLIN1, while downregulating P62. Collectively, TRIM13 OE inhibited the proliferation and migration of HCC cells through autophagy.

Cancer biobank studies can inform the natural history of cancer and possibilities for earlier detection. The authors investigated the detectability of a cell-free DNA methylation-based cancer signal in biobanked plasma samples from the large American Cancer Society Cancer Prevention Study 3.

Mammalian reproductive function is dependent upon gonadal steroid hormone feedback within the hypothalamic-pituitary-gonadal (HPG) axis. In polycystic ovary syndrome (PCOS), impaired progesterone (P4) negative feedback leads to hyperactive pulsatile secretion of luteinising hormone (LH) and impaired reproductive function. Although the precise upstream neuronal network modulating P4 negative feedback remains undefined, gamma-aminobutyric acid (GABA)ergic neurons in the arcuate nucleus (ARC) have been implicated. To identify the critical location of P4 negative feedback, we knocked out progesterone receptors (PR) specifically from GABA neurons by genetic cross (VGAT-Cre; PRfl/fl) or specifically from the arcuate nucleus by stereotaxic AAV-Cre delivery to PRfl/fl mice and assessed HPG axis function. Females with GABA-specific PR knockout (GABAPRKO) exhibited delayed vaginal opening and fewer estrous cycles compared to controls, but LH pulse frequency and P4 negative feedback were unaffected. In contrast, females with AAV-Cre-mediated knockdown of PR specifically in the ARC exhibited increased LH pulse frequency in comparison to control and AAV-Cre off-target animals. ARC-specific PR knockdown also resulted in significantly decreased estrous cycle frequency, increased cycle length, reduced time spent in proestrus, and impaired P4 negative feedback, but no change in testosterone levels. These data show that reduced PR signalling in the ARC of adult female mice is sufficient to drive hyperactivity within the HPG axis and mimic some but not all reproductive features of PCOS. The subtle reproductive deficits in GABAPRKO may reflect compensatory mechanisms or the involvement of multiple neuronal phenotypes in P4 negative feedback. Together, this work supports the ARC as a critical site for P4 negative feedback regulation of the reproductive axis.