N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic mRNA, plays a crucial role in regulating RNA metabolism and gene expression. Among m6A regulators, METTL3 functions as the catalytic core of the m6A methyltransferase complex and has emerged as a critical epitranscriptomic modulator in cancer. An expanding body of evidence demonstrates that METTL3 is aberrantly expressed in various malignancies, contributing to tumor progression, metastasis, stemness, immune evasion, and resistance to chemotherapy and targeted therapies. Nonetheless, its role remains highly context-dependent, exerting either oncogenic or tumor-suppressive effects based on cancer type and the microenvironment. This review offers an in-depth analysis of the molecular structure and biological functions of METTL3, summarizes its expression profiles and prognostic significance in major human cancers, and examines the mechanisms through which METTL3 modulates tumor biology. In addition, current advancements in the therapeutic targeting of METTL3 are discussed, including small-molecule inhibitors, such as STM2457, their preclinical efficacy, and the challenges and future prospects for clinical translation.

Long non-coding ribonucleic acids (LncRNAs) are larger than 200 nucleotides and resemble messenger ribonucleic acids (mRNAs), but they do not code for proteins. In both cell development and physiological cell function, LncRNAs have crucial biological functions. Consequently, cancer entails the disruption of their biological function. Many people die from lung cancer because it is diagnosed late, spreads to other parts of the body, and has a high treatment failure rate. Because they can be involved in either oncogenic or tumor-suppressing functions, LncRNAs are quickly becoming core molecules in lung cancer. Since LncRNAs are long-lasting in blood, they can be utilized as non-invasive diagnostic tools for cancer at an early stage. We review the latest research that has brought together evidence from real-world observations concerning the processes through which LncRNAs work in cancer formation, how they allow cancer to develop drug resistance, and how they can be used as possible diagnostic tools and markers of outcome, with a focus on lung cancer. We also cover some of the ongoing treatment strategies that can target LncRNAs. As seen from what has been laid out here, the examination of LncRNAs in lung cancer with protein-coding genes could provide evidence for a further elucidation of the molecular events behind the disease as well as its progression, and the potential for a new therapeutic pathway.

Colorectal carcinogenesis and progression are closely associated with metabolic dysregulation. The role of MOGAT2 in colorectal cancer (CRC) advancement and its underlying metabolic mechanisms remain unclear. This study aimed to explore how MOGAT2 influences tumorigenesis by modulating lipid metabolism.

Rectal cancer is one of the most common malignant tumors in China, with more than half of patients diagnosed at the locally advanced stage. Currently, the standard treatment for locally advanced rectal cancer (LARC) primarily involves neoadjuvant chemoradiotherapy followed by radical surgery. The advent of immune checkpoint inhibitors has revolutionized the neoadjuvant treatment landscape for mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) rectal cancer. However, most rectal cancer patients exhibit mismatch repair-proficient/microsatellite stable (pMMR/MSS) status and show poor responsiveness to immunotherapy. In recent years, multiple studies have demonstrated that neoadjuvant short-course radiotherapy followed by chemotherapy and immunotherapy can improve the pathological complete response rate in pMMR/MSS LARC patients. Nevertheless, controversies persist regarding patient selection, efficacy evaluation, adverse event management, postoperative adjuvant therapy, and follow-up strategies. Considering the Colorectal Surgery Group of the Surgery Branch of the Chinese Medical Association, in collaboration with the Colorectal and Anal Surgery Committee of the Chinese Research Hospital Association, the Chinese Colorectal Cancer Clinical Research Collaborative Group, and related experts, has developed this consensus document by referencing domestic and international research advancements. The aim is to provide standardized guidance for the clinical application of this treatment approach.

Aging constitutes a major risk factor for pan-cancer development, with epidemiological studies indicating that 60% of new malignancies occur in adults age 65 and older. This review synthesizes cutting-edge insights from single-cell sequencing databases (e.g., TCGA and GEO) that decipher how aging reprograms the tumor microenvironment (TME) to fuel carcinogenesis. Single-cell RNA sequencing (scRNA-seq) has revealed that senescent cell subpopulations (e.g., CDKN2A+/LMNB1- cells) accumulate in aged tissues at frequencies up to 15%, driving genomic instability and secrete pro-tumorigenic senescence-associated secretory phenotype (SASP) factors (IL-6 and TGF-β). These factors remodel the TME by inducing fibroblast activation and extracellular matrix degradation, accelerating metastasis by 40-70% in murine models. Crucially, immunosenescence diminishes anti-tumor immunity, with scRNA-seq profiling showing 40-60% increases in exhausted PD-1+ T cells and immunosuppressive myeloid cells in aged TMEs. Pan-cancer analyses have identified conserved aging gene signatures (e.g., p16INK4a upregulation in 12+ cancer types) that correlate with 30-50% poorer survival. While technical challenges persist - including batch effects in scRNA-seq data and low senescent cell abundance (< 5%) - emerging solutions like deep learning can enhance detection sensitivity. Therapeutically, senolytic strategies deplete senescent cells, improving drug response by 3.5-fold in preclinical trials. Future research must integrate multi-omics and AI to examine aging-related targets, advancing personalized interventions for aging-associated malignancies.

Breast cancer stem cells (BCSCs) represent a distinctive subpopulation within breast cancer that exhibit stem cell-like characteristics, including self-renewal capability and multipotent differentiation. They are recognized as the central drivers of tumor initiation, progression, metastasis, and drug resistance. In-depth investigation of BCSCs represents a crucial avenue for overcoming the current therapeutic limitations in breast cancer. This review comprehensively summarizes recent advances in BCSCs-related research, focusing on key areas such as surface marker identification, mechanisms underlying tumor recurrence and metastasis, core regulatory signaling networks, and therapy resistance. Furthermore, it discusses potential clinical strategies targeting BCSCs, and explores future directions for precision medicine based on hetogeneity and dynamic regulation of BCSCs. These insights provide important theoretical foundations for the development of targeted therapies against breast cancer.

To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population.

To investigate the prognostic significance of PDZ-binding kinase (PBK) in pan-cancer and its potential as a therapeutic target for pancreatic cancer.

To evaluate the regulatory effects of lncRNA LINC00261 on proliferation, invasion, and metastasis of esophageal squamous cell carcinoma (ESCC) cells.

Uncommon EGFR mutations, including G719X, L861Q, S768I, and compound mutations, present therapeutic challenges due to limited prospective evidence and variable drug sensitivity. Although later-generation (i.e., second- and third-) EGFR-TKIs have shown benefit in some subtypes, real-world data is limited.

Spatial transcriptomics (ST) integrates spatial data with transcriptomic information, providing high-resolution maps of gene expression within tissue contexts. It has revolutionized studies on cellular function and disease mechanisms, particularly in cancer and immunology. We conducted a bibliometric analysis of 1197 publications from the Web of Science (2015-24), focusing on publication trends, journal distribution, and keyword analysis to identify key research areas in ST. ST publications surged from 2021, with 500 papers in 2023. Five of the top 10 journals are from the Nature Publishing Group. Keyword analysis identified emerging trends like "tumor microenvironment," "immune infiltration," and "biomarker," highlighting ST's expanding role in cancer and immunology. International collaboration among multidisciplinary teams is crucial for maximizing ST's potential, and understanding its trends will guide its future impact. Large language models can further enrich the results of bibliometric research, making the findings of bibliometrics more comprehensive and specific.

Cervical cancer, a prevalent female malignancy, is treated with surgery, radiotherapy, chemotherapy, immunotherapy and targeted therapy. Yet, prognosis remains influenced by multiple factors. Epithelial-mesenchymal transformation (EMT) is an important link in the malignant progression of tumor cells and has an important impact on the progression and prognosis of cervical cancer. This study aimed to analyze effect of Baofukang suppository on the related indexes of EMT of tumor cells in cervical cancer patients. Eighty patients with cervical cancer received in The First Affiliated Hospital of Anhui Medical University from March 2020 to March 2022 were randomized into a control group (chemotherapy alone, n=40) and a study group (chemotherapy + Baofukang, n=40). Post-treatment, the study group showed significantly lower mRNA levels of EMT markers Vimentin and N-cadherin, and higher E-cadherin and β-catenin (p<0.05). Additionally, interleukin-6 (IL-6) decreased while interleukin-2 (IL-2) and interferon-γ (INF-γ) increased (p<0.05). Immune function improved, with higher CD3+, CD4+ and CD4+/CD8+ ratios, and lower CD8+ (p<0.05). The adverse reactions between two groups were not unconspicuous (p>0.05). The adjuvant therapy of Baofukang Suppository can effectively regulate the relevant indexes of tumor cell EMT, delay or prevent the EMT of tumor cells.

In acute myeloid leukemia (AML), measurable residual disease (MRD) assessment is essential for predicting relapse and guiding therapy decision-making. Nucleophosmin 1 (NPM1) mutations are reliable MRD markers but apply to only ∼30% of patients with AML. Wilms tumor 1 (WT1) expression monitoring is applicable to a broader population but the European LeukemiaNet (ELN) threshold of 50 WT1 copies per 104 ABL copies (0.5%) may be too high, which limits sensitivity.

The regulation of gene expression through chromatin architecture plays a critical role in acute myeloid leukemia (AML). In this study, the influence of MAPK3 on CTCF-mediated chromatin interactions in AML was examined, focusing on gene regulation and chromatin architecture. Immunoprecipitation coupled with mass spectrometry (IP-MS) was conducted to identify CTCF-binding proteins in AML cell lines. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to assess the impact of MAPK3 modulation on CTCF DNA binding, following treatment with an MAPK3 activator or inhibitor. Additionally, chromatin interactions were evaluated using 3C-qPCR, and specific enhancer sites at the SKAP2 locus were deleted using CRISPR-Cas9. Results demonstrated that IP-MS identified MAPK3 as a key CTCF-binding protein, indicating its potential role in AML chromatin regulation. MAPK3 significantly influences CTCF binding at distal intergenic regions upstream of SKAP2, as confirmed by ChIP-seq. Chromatin interaction analyses revealed that CTCF-regulated enhancer-promoter interactions at SKAP2 are modulated by MAPK3 activity. Furthermore, deletion of enhancer regions E4 and E6 led to decreased SKAP2 expression. These findings highlight the critical role of MAPK3 in regulating CTCF-mediated chromatin interactions and suggest that targeting MAPK3-regulated chromatin remodeling could be a novel therapeutic strategy for AML.

Bladder cancer has notable heterogeneity. The urine-based fluorescence in situ hybridization (FISH) test can detect bladder cancer noninvasively. In this study, we aimed to construct a nomogram based on FISH results and clinical features (referred to as the FISH-clinical model) to predict the overall survival (OS) of bladder cancer patients following radical cystectomy (RC).

Acute myeloid leukemia (AML) exhibits pronounced heterogeneity, necessitating deep molecular characterization for precision therapy. Lactate metabolism and histone lactylation, influencing tumor biology via epigenetic regulation and immune microenvironment remodeling, represent an emerging focus. This study combines single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (bulk RNA-seq) data to investigate the prognostic value of lactate/lactylation-associated genes (LL-genes, defined as genes involved in lactate metabolism and histone lactylation regulation) in AML. Specifically, Seurat was utilized for scRNA-seq clustering with cell annotation/validation via the TISCH2 database. Gene Set Variation Analysis (GSVA) assessed lactate/lactylation pathway activity. In bulk RNA-seq, ConsensusClusterPlus enabled molecular subtyping, while ten machine learning algorithms constructed a prognostic model. scRNA-seq revealed specific LL-gene overexpression in malignant progenitors, concomitant with elevated lactate metabolism-lactylation activity (LML-CAS; Lactate Metabolism-Lactylation Modification Combined Activity Score), enhanced metabolic-inflammatory synergy, and immunosuppression (increased Tregs/M2 macrophages). Molecular subtyping identified two clusters (A/B) exhibiting divergent survival outcomes (Cluster A: poorer prognosis). An optimized 7-gene prognostic model demonstrated high accuracy, predicting reduced chemotherapy response among high-risk patients. Transcriptomic profiling indicated lactylation-associated immunosuppression (e.g., downregulated CXCL9/10-CXCR3 axis, enrichment of T cell exhaustion markers) and heightened in silico-predicted sensitivity to BCL-2/FGFR inhibitors (ABT-737/AZD4547) in high-risk patients. qRT-PCR confirmed RNA-level dysregulation of key LL-genes (IFI16, THOC2, HIST1H2BD, ARPP19), aligning with bioinformatic predictions. Western blot analysis further validated aberrant protein expression of IFI16 and THOC2 in AML specimens, reinforcing their dysregulation. Collectively, integrated analyses uncovered lactate/lactylation-associated heterogeneity in AML. Our machine learning-based prognostic model predicts survival, therapeutic response, and drug sensitivity, suggesting a potential strategy for precision therapeutics in AML.

Thyroid carcinoma is the most common malignant endocrine tumour, and its prevalence has been on the rise in recent years. However, mechanisms underlying the metastasis of thyroid carcinoma and candidate biomarkers remain elusive. In this study, we screened genes involved in the virulence and metastasis of papillary thyroid carcinoma (PTC).

COMPEL (NCT04765059) was a global, randomized, double-blind study that evaluated osimertinib plus chemotherapy versus placebo plus chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) following non-central nervous system (CNS) progression on first-line osimertinib.

Disulfidptosis, a novel form of regulated cell death (RCD), represents a promising strategy for cancer therapy. However, identifying its regulators remains a key challenge. In this study, we constructed a genome-wide disulfidptosis signature (DS) model using known regulators and large-scale human gene expression data comprising 1454 studies and 272,445 samples. This model predicted disulfidptosis propensity across 33 cancer types and highlighted DS differences across tissues and organs. Functional analysis focused on the top 1 % of high-DS and low-DS genes, revealing their sensitivity to perturbations through simulated overexpression and knockout experiments. In hepatocellular carcinoma (HCC), NRF1 and NRF2 were identified as key disulfidptosis regulators, functioning as a desensitizer and sensitizer, respectively, as validated through gene knockouts, cellular morphology, and functional analyses. Additionally, the ketogenic diet significantly increased cellular sensitivity to disulfidptosis under glucose starvation by promoting metabolic adaptation. Using network pharmacology, small-molecule compounds influencing disulfidptosis were identified. Among these, NR-CL was validated as a disulfidptosis desensitizer, while lomerizine and clioquinol were confirmed as sensitizers through gene expression predictive analyses and cellular functional validation. These findings lay a robust foundation for uncovering novel regulatory mechanisms of disulfidptosis and provide practical strategies for enhancing cancer chemotherapy through targeted interventions.

Lung adenocarcinoma (LUAD), the predominant non-small cell lung cancer subtype, exhibits high mortality due to metastasis and therapeutic resistance. While circular RNAs (circRNAs) are implicated in oncogenesis, their functional mechanisms and upstream regulation in LUAD remain incompletely characterized. This study identifies circDNAJC16 (hsa_circ_0000018) as significantly downregulated in advanced-stage LUAD (Stage III-IV vs. I-II, p = 0.001), where its low expression independently predicts poor survival (HR = 1.93, p = 0.043). Functional characterization demonstrates that circDNAJC16 overexpression suppresses in vivo tumor growth (volume reduction: 26.56 %, p < 0.001) through cytoplasmic sequestration of oncogenic miR-93-5p, thereby activating CDKN1A/p21 to induce G0/G1 cell cycle arrest and inhibit proliferation, while concurrently suppressing metastasis via epithelial-mesenchymal transition (EMT) regulation. Crucially, the RNA-binding protein eIF4A3 binds upstream flanking introns of the host DNAJC16 pre-mRNA, driving selective nuclear retention of circDNAJC16 and redirecting linear DNAJC16 mRNA to the cytoplasm - a bifurcation mechanism essential for tumor suppression. These findings identify circDNAJC16 downregulation as a negative prognostic indicator in LUAD and reveal its dual tumor-suppressive roles: cytoplasmic sequestration of miR-93-5p activating CDKN1A-mediated cell cycle arrest, coupled with eIF4A3-governed nuclear retention controlling functional subcellular localization. Significantly, this work is the first to demonstrate eIF4A3-mediated circRNA compartmentalization, establishing circDNAJC16 as a novel prognostic biomarker and therapeutic target for LUAD.