First-degree relatives (FDRs) of hereditary colorectal cancer are at an increased risk of cancer and receiving early detection and surveillance on malignancies is an efficacious strategy to reduce cancer-related morbidity and mortality. But there is rare information on screening in this cancer high-risk group in China.

Leukemia is a serious problem affecting both children and adults, leading to death if left untreated. Leukemia is a kind of blood cancer described by the rapid proliferation of abnormal blood cells. An early, trustworthy, and precise identification of leukemia is important to treating and saving patients' lives. Acute and myelogenous lymphocytic, chronic and myelogenous leukemia are the four kinds of leukemia. Manual inspection of microscopic images is frequently used to identify these malignant growth cells. Leukemia symptoms include fatigue, a lack of enthusiasm, a dull appearance, recurring illnesses, and easy blood loss. Identifying subtypes of leukemia for specialized therapy is one of the hurdles in this area. The suggested work predicts and classifies leukemia subtypes in gene data CuMiDa (GSE9476) using feature selection and ML techniques. The Curated Microarray Database (CuMiDa) collected 64 samples representing five classes of leukemia genes out of 22283 genes. The proposed approach utilizes the 25 most differentiating selected features for classification using machine and deep learning techniques. This study has a classification accuracy of 96.15% using Random Fores, 92.30 using Linear Regression, 96.15% using SVM, and 100% using LSTM. Deep learning methods have been shown to outperform traditional methods in leukemia gene classification by utilizing specific features.

Glioblastomas utilize malignant gene expression pathways to drive growth. Many of these gene pathways are not directly accessible with molecularly targeted pharmacological agents. Chromatin-modifying compounds can alter gene expression and target glioblastoma growth pathways. In this study, we utilize a systematic screen of chromatin-modifying compounds on a panel of patient-derived glioblastoma lines to identify promising compounds and their associated gene targets.

In human acute myeloid leukemia (AML), mutations of isocitrate dehydrogenase-1 (IDH1) often co-occur with NPM1 mutations, and less frequently with FLT3 mutations. To investigate whether the effects of IDH1 mutation differ according to the specific co-occurring mutation, we generated two strains of double knock-in mutant mice. Idh1R132H combined with Npm1c induced overt AML, whereas Idh1R132H plus Flt3ITD resulted in Flt3ITD-driven myelo- or lymphoproliferation that was minimally affected by Idh1R132H and rarely generated AML. Gene expression profiling revealed differences between Idh1R132H;Npm1c cells and Idh1R132H;Flt3ITD cells and suggested altered heme metabolism and immune responses in the former. The profile of Idh1R132H;Npm1c cells corresponded to that of human IDH-mutated AML cells, particularly those resistant to inhibitors of mutant IDH. Compared to treatment with a menin inhibitor, IDH1-targeted therapy of Idh1R132H;Npm1c AML-bearing mice was less efficacious in improving cell differentiation and extending survival. The differential cooperation of Idh1R132H with Npm1c vs. Flt3ITD may have implications for the devising of subtype-specific treatments for human AML.

Ewing sarcoma (EwS) is an aggressive cancer of bone and soft tissue that predominantly affects children and young adults. A chromosomal translocation joins the low-complexity domain (LCD) of the RNA-binding protein EWS (EWSLCD) with the DNA-binding domain of Friend leukemia integration 1 (FLI1DBD), creating EWS::FLI1, a potent fusion oncoprotein essential for EwS development and responsible for over 85% of EwS tumors. EWS::FLI1 forms biomolecular condensates in vivo and promotes tumorigenesis through mediation of aberrant transcriptional changes and by interfering with the normal functions of nucleic acid-binding proteins like EWS through a dominant-negative mechanism. In particular, the expression of EWS::FLI1 in EwS directly interferes with the biological functions of EWS leading to alternate splicing events and defects in DNA-damage repair pathways. Though the EWSLCD is capable of phase separation, here we report a direct interaction between FLI1DBD and EWSLCD that enhances condensate formation and alters the physical properties of the condensate. This effect was conserved for three related E-twenty-six transformation-specific (ETS) DNA-binding domains (DBDs) while DNA binding blocked the interaction with EWSLCD and inhibited EWS::FLI1 condensate formation. NMR spectroscopy and mutagenesis studies confirmed that ETS DBDs transiently interact with EWSLCD via the ETS DBDs "wings." Together these results revealed that ETS DBDs, particularly FLI1DBD, enhance EWSLCD condensate formation and rigidity, supporting a model in which electrostatic and structural interactions drive condensate dynamics with implications for EWS::FLI1-mediated transcriptional regulation in EwS.

MicroRNAs (miRs) are small non-coding RNAs that have been extensively reported to be involved in multiple myeloma (MM) pathogenesis and progression. While the precise role of miRs in MM remains to be fully elucidated, they have demonstrated significant potential as prognostic markers in various other cancers. This study aimed to investigate the relationship between miR-21, miR-181a, and miR-23b expression before autologous hematopoietic stem cell transplantation (AHSCT) and post-transplant early relapse (ER) incidence in MM patients.

Glioma is a devastating type of brain tumor with high malignancy, an extremely high mortality rate, and a recurrence risk. Molecular markers are known to have a major role in classification, prognosis, survival rate, and therapy determination for different glioma subtypes. The aim of this study was to investigate the association of gliomas' main genetic markers: isocitrate dehydrogenase (IDH) mutations and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status with the survival rate in Russian patients with glioblastoma and other glial tumors. According to histological subtype, included glioma patients were divided into two groups: glioblastoma (n = 90) and other gliomas (n = 40). IDH mutations were screened by high-resolution melting-curve analysis (HRM) followed by direct sequencing, and MGMT methylation was detected with pyrosequencing. Our data showed that IDH mutations are significantly more frequent among patients with other gliomas compared to glioblastoma patients (p < 0.001). Patients with mutated IDH gene have a significantly higher progression-free survival (PFS) and overall survival (OS) rates than those with wild-type genes. MGMT promoter methylation status was found to be significantly associated with PFS, but not OS. The presence of IDH mutation with a methylated MGMT promoter significantly increased patients' PFS and OS. To our knowledge, this is the first study to investigate the association of IDH and MGMT genetic biomarkers with glioma in the Russian population. Our findings could be used in future studies to improve glioma prognosis and classification and reach a personalized treatment protocols depending on multiple molecular biomarkers.

Twenty-five percent of all aggressive angiomyolipomas (AMLs) are related to tuberous sclerosis. Our patient was a 42-year-old man with tuberous sclerosis and a medical history of a benign AML in the left kidney. Presently, an epithelioid AML was detected in his right kidney and, despite our conducting extensive surgery, a large pulmonary metastasis with mediastinal lymph node involvement followed 20 months later. Close follow-up of the patient is advised when epithelioid cells are observed in angiomyolipoma. Immunohistochemistry for mismatch repair proteins showed that PMS2, MSH2, and MSH6 were absent in both the tumor and normal kidney. Microsatellite instability may contribute along with a mutation of TSC gene to the oncogenic events leading to AML.

Gastrointestinal cancer (GI) is one of the most common and deadly cancers worldwide. In the present study, we assessed the association between single nucleotide polymorphisms (SNPs) within nucleotide excision repair (NER) pathway genes (xeroderma pigmentosum complementation group C [XPC], xeroderma pigmentosum complementation group G [XPG], and xeroderma pigmentosum complementation group D [XPD]) and the GI cancer risk in the rural population of Maharashtra.

Gallbladder cancer (GBC) is a rare but aggressive malignancy, often detected late due to early asymptomatic stages. Understanding cellular and molecular changes from normal tissue to high-grade intraepithelial neoplasia (HGIN) and invasive GBC is vital for identifying early biomarkers and therapeutic targets.

Although there have been multiple lines of drugs for gastrointestinal stromal tumors (GISTs), the drug response depends on the progressive tumors' biological behaviors and secondary mutations.

Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a rare disease which is more often diagnosed in children and adolescents than adults. Activation of the MAPK/ERK pathway is implicated in the majority of cases, and BRAF fusions are the most common genetic alteration. BRAF fusions result in dimerization and constitutive downstream MAPK/ERK activity, against which type I RAF inhibitors have limited efficacy. Type II RAF inhibitors stabilize RAF in an inactive conformation and inhibit both dimer protomers, thus inhibiting downstream MAPK/ERK activity in the setting of BRAF fusions.

Circulating tumor DNA (ctDNA) acts as an early biomarker of the efficacy of androgen receptor signaling inhibitor (ARSI) therapy. In this study, we aimed to reveal if ctDNA can supplement imaging to better predict metastasis burden and radiographic progression disease (PD) in metastatic castration-resistant prostate cancer (mCRPC).

Chaetocin, a fungal metabolite, exerts notable antiproliferative effects against solid tumors by triggering apoptosis; however, the mechanisms underlying its effects remain unclear. As tumor necrosis factor (TNF)‑related apoptosis‑inducing ligand (TRAIL) promotes apoptosis in certain types of tumor, the present study aimed to explore the sensitizing effects of chaetocin in TRAIL‑induced apoptosis in human glioblastoma cells and the underlying mechanism. Human glioblastoma cells (U343MG, U87MG, U251MG, and T98G) and embryonic kidney cells (HEK293) were co‑treated with chaetocin and TRAIL, followed by assessment of cell viability. The results from viability and apoptosis assays demonstrated a significant increase in caspase-dependent apoptosis in glioblastoma cells, but not in HEK293 cells, upon co-treatment with chaetocin and TRAIL. Additionally, death receptor 5 (DR5) expression analysis demonstrated that co‑treatment with chaetocin and TRAIL upregulated DR5 expression in a dose‑ and time‑dependent manner by increasing the stability of DR5 on the cell surface. In glioblastoma cells, small interfering RNA‑mediated DR5 knockdown markedly suppressed chaetocin/TRAIL‑induced apoptosis. Moreover, chaetocin enhanced reactive oxygen species (ROS) production, which facilitated TRAIL‑mediated apoptosis by enhancing DR5 upregulation. Thus, chaetocin sensitized the human glioblastoma cell lines U87MG and T98G to TRAIL‑mediated apoptosis by upregulating DR5 expression through ROS-mediated mechanisms. The present findings underscore chaetocin as a potential novel therapeutic agent for glioblastoma.

Triple‑negative breast cancer (TNBC) exhibits a high degree of malignancy and a propensity for metastasis, ultimately resulting in unfavorable patient outcomes. Curcuma phaeocaulis Valeton is a common herb used in traditional Chinese medicine to treat TNBC. Curcumenol (Cur) is a natural compound derived from C. phaeocaulis Valeton, the effects of which on breast cancer remain under‑reported. The present study elucidated that Cur could effectively inhibit the survival ability of TNBC cells and enhance their sensitivity to paclitaxel. Western blotting (WB) further revealed that Cur modulated apoptosis and epithelial‑mesenchymal transition (EMT) in TNBC. Findings from animal experiments further validated these observations. In the established TNBC mouse model, Cur was shown to exert an inhibitory effect on tumor growth, effectively attenuate EMT and substantially reduce the incidence of lung metastasis. Integrated analyses using RNA sequencing, WB and reverse transcription‑quantitative polymerase chain reaction demonstrated that Cur markedly downregulated the expression levels of solute carrier family 7 member 11 (SLC7A11), phosphorylated‑NF‑κB and TGF‑β. Molecular docking studies further validated that Cur can establish stable interactions with SLC7A11. In‑depth bioinformatics analysis revealed a positive association between high SLC7A11 expression and reduced disease‑free survival in patients with breast cancer. Additionally, in TNBC cells, Cur was revealed to reduce the mitochondrial membrane potential and promote the accumulation of lipid reactive oxygen species. Subsequent experimental investigations demonstrated that Cur can counteract the inhibitory influence of ferrostatin‑1 on ferroptosis. These findings strongly implied a potential underlying mechanism, suggesting that Cur may impede the malignant progression of TNBC via the modulation of ferroptosis. In conclusion, the findings of the present study underscore the marked efficacy of Cur in hampering the progression of TNBC by suppressing the SLC7A11/NF‑κB/TGF‑β signaling pathway.

Decidual protein induced by progesterone (DEPP1) was identified to exert heterogeneous functions in several cancers, whereas its role in gastric cancer (GC) remains elusive. In the present study, differential expression analysis was conducted using three Gene Expression Omnibus datasets (GSE54129, GSE26942 and GSE3438). Validation of DEPP1 expression was performed using reverse transcription‑quantitative PCR, western blotting and immunofluorescence. Kaplan‑Meier survival and Cox regression analyses were employed to assess the association between DEPP1 expression and the prognosis of patients with GC. Immune infiltration analysis was conducted to explore the correlation between DEPP1 and the tumor microenvironment. The potential of DEPP1 to promote oxaliplatin resistance was assessed using flow cytometry, western blotting, and subcutaneous mouse models. DEPP1 was found to be significantly upregulated in the aforementioned cohorts, which was consistent with the clinical specimens of the present study, and it emerged as an independent risk factor for poor overall survival in patients with GC. A prognostic nomogram was developed to improve prognosis prediction. High DEPP1 expression correlated with increased infiltration of cancer‑associated fibroblasts, endothelial cells, and M2 macrophages, contributing to the development of a stroma‑rich and immunosuppressive microenvironment in GC. Furthermore, high DEPP1 expression was associated with reduced sensitivity to chemotherapy drugs in patients with GC. In vitro and in vivo experiments highlighted DEPP1's crucial role in promoting oxaliplatin resistance in GC. In conclusion, DEPP1 is identified as a promising prognostic biomarker linked to a stroma‑rich and immunosuppressive microenvironment, and it is critical in driving oxaliplatin resistance in GC. These findings may inform personalized therapeutic strategies for patients with GC.

Metabolic reprogramming represents a hallmark of malignant tumors, manifested through progressive alterations in nutrient utilization patterns during oncogenesis. As fundamental constituents of biological membranes, essential components of signaling pathways, and critical energy substrates, lipids undergo comprehensive metabolic restructuring in neoplastic cells. This lipid remodeling confers enhanced adaptability to sustain uncontrolled proliferation while promoting aggressive migratory phenotypes. Farnesoid X receptor (FXR), a ligand‑activated nuclear receptor responsive to bile acid (BA) derivatives and cholesterol metabolites, orchestrates key aspects of lipid homeostasis. Its regulatory network encompasses cholesterol/BA metabolism, fatty acid (FA) metabolism and plasma lipoprotein trafficking pathways. Emerging evidence positions FXR as a pleiotropic modulator in oncogenesis, with dysregulated expression patterns documented across multiple tumor lineages and premalignant lesions. This mechanistic understanding has propelled FXR‑targeted therapeutics into the forefront of precision oncology development. The present review critically examines the FXR‑lipid axis in lipid‑enriched malignancies, with particular emphasis on its regulatory circuitry governing BA flux and FA turnover.

CD40 expression in esophageal cancer (EC) is linked to poor prognosis, although its molecular role remains unclear. The present study explored the function of CD40 in EC progression and metastasis, focusing on its interaction with CD154 and the upregulation of MMP‑9. CD40 expression was confirmed in EC cell lines using quantitative PCR, western blotting, flow cytometry and immunocytochemistry. Functional assays showed that recombinant soluble CD154 stimulation enhanced the migration and invasion of CD40‑overexpressing EC cells without affecting viability. Co‑culture experiments with platelets demonstrated that platelet‑derived CD154 acted on CD40‑overexpressing esophageal cancer cells, leading to upregulation of MMP‑9 secretion, potentially driving tumor invasiveness. Serum analysis of patients who underwent esophagectomy revealed that low MMP‑9 levels were associated with longer survival in pathological Stage I, whereas the opposite trend was observed in stages II‑IV. These findings indicated that CD40 activation enhanced tumor cell invasiveness through MMP‑9 upregulation. This dual role of CD40, enhancing antitumor immunity via its expression on antigen‑presenting cells, while promoting tumor invasiveness through MMP‑9 secretion when expressed on esophageal cancer cells, may complicate immunotherapeutic strategies targeting CD40, as such interventions could inadvertently promote malignancy within the tumor microenvironment.

Immunotherapy has become the first-line treatment for metastatic mismatch repair deficient (dMMR) colorectal cancer. The efficacy and safety of neoadjuvant immunotherapy for the treatment of non-metastatic dMMR colorectal cancer remain unclear. In this article, we explore the clinical effect and safety of neoadjuvant immunotherapy for non-metastatic dMMR colorectal cancer.

Recent studies have highlighted dysregulated tRNA modifications in the reprogramming of tumor translation. Cytosolic thiouridylase subunit 2 (CTU2) is an essential and conserved enzyme that modifies tRNA at the wobble position. However, the relationship between CTU2 expression and various cancer types remains insufficiently explored.