Despite considerable recent advancements in colorectal cancer (CRC) therapy, the prognosis of patients with advanced disease remains poor. Further understanding of the molecular mechanisms and treatment strategies of this disease is required. Zinc finger protein 692 (ZNF692), also known as AREBP and Zfp692, was first reported to have an important role in gluconeogenesis. A recent study demonstrated that ZNF692 is overexpressed in lung adenocarcinoma (LUAD) tissues and that ZNF692 knockdown inhibited LUAD cell proliferation, migration, and invasion both in vitro and in vivo . However, the role of ZNF692 in colon adenocarcinoma (COAD) remains unclear. The present study revealed that ZNF692 was upregulated in COAD tissues and cells and that high ZNF692 expression was significantly correlated with lymph node metastasis, distant metastasis and tumor stage in COAD patients. Gain- and loss-of-function experiments were employed to identify the function of ZNF692 in COAD progression. In vitro and in vivo assays revealed that ZNF692 promoted COAD cell proliferation, migration and invasion. Furthermore, western blot analysis demonstrated that the effects of ZNF692 were mediated by upregulating cyclin D1, cyclin-dependent kinase 2 (CDK2) and matrix metalloproteinase-9 (MMP-9) and by downregulating p27 Kip1 through the phosphoinositide 3-kinase/AKT signaling pathway. Collectively, these data indicated that ZNF692 may serve as a novel oncogene and a potential treatment target in COAD patients.
Systemic lupus erythematosus (SLE) is a multisystem autoimmune inflammatory condition that affects multiple organs and provokes extensive and severe clinical manifestations. Lupus nephritis (LN) is one of the main clinical manifestations of SLE. It refers to the deposition of immune complexes in the glomeruli, which cause kidney inflammation. Although LN seriously affects prognosis and represents a key factor of disability and death in SLE patients, its mechanism remains unclear. The NACHT, leucine-rich repeat (LRR), and pyrin (PYD) domains-containing protein 3 (NLRP3) inflammasome regulates IL-1β and IL-18 secretion and gasdermin D-mediated pyroptosis and plays a key role in innate immunity. There is increasing evidence that aberrant activation of the NLRP3 inflammasome and downstream inflammatory pathways play an important part in the pathogenesis of multiple autoimmune diseases, including LN. This review summarizes research progress on the elucidation of NLRP3 activation, regulation, and recent clinical trials and experimental studies implicating the NLRP3 inflammasome in the pathophysiology of LN. Current treatments fail to provide durable remission and provoke several sides effects, mainly due to their broad immunosuppressive effects. Therefore, the identification of a safe and effective therapeutic approach for LN is of great significance. Phytochemicals are found in many herbs, fruits, and vegetables and are secondary metabolites of plants. Evidence suggests that phytochemicals have broad biological activities and have good prospects in a variety of diseases, including LN. Therefore, this review reports on current research evaluating phytochemicals for targeting NLRP3 inflammasome pathways in LN therapy.
ObjectiveThis study evaluated the association between body composition and clinical parameters and prognosis in patients with colorectal cancer (CRC) treated by radical resection.MethodsBaseline data on patient age, body mass index (BMI), bowel obstruction and tumor-related factors were collected retrospectively. Body composition parameters such as visceral fat area (VFA), total abdominal muscle area (TAMA), muscle attenuation (MA), posterior renal fat thickness (PPNF) and intermuscular fat area (IMF) are measured using Computed tomography (CT) scans. We also propose a new predictor of linear skeletal muscle index (LSMI) that can be easily measured clinically at CT. Follow-up endpoints were disease-free survival and all-cause death. We follow up with patients in hospital or by telephone. Univariate and multifactorial Cox proportional hazards analyses were performed to identify risk factors associated with prognosis. Survival analysis was performed using the Kaplan-Meier method and a nomogram was established to predict survival.ResultsA total of 1761 patients (median age 62 years) with CRC were enrolled in our study, of whom 201 had intestinal obstruction and 673 had a BMI > 24.0. Among all patients, the 3- and 5-year disease-free survival rates were 84.55% and 68.60% respectively, and the overall survival rates were 88.87% and 76.38%. Overall survival was significantly correlated with MA, LSMI, SMI, Tumor size, N stage, metastasis and adjuvant therapy by Cox regression analysis (p < 0.05). The risk of tumor progression was significantly associated with MA, VFA, LSMI, SMI, Male, N stage, metastasis and adjuvant therapy (p < 0.05). In addition, based on the Chinese population, we found that female patients with MA < 30.0 HU, LSMI < 18.2, and SMI < 38.0 had a worse prognosis, male patients with MA < 37.6 HU, LSMI < 21.9, and SMI < 40.3 had a poorer prognosis.ConclusionOur findings suggest that linear skeletal muscle index and MA can be used as new independent predictors for colorectal cancer patients treated with radical surgery, and that baseline data such as body composition parameters, LSMI and tumor-related factors can collectively predict patient prognosis. These results could help us to optimize the management and treatment of patients after surgery.
BackgroundColon adenocarcinoma (COAD) is a prevalent malignancy that causes significant mortality. Microsatellite instability plays a pivotal function in COAD development and immunotherapy resistance. However, the detailed underlying mechanism requires further investigation. Consequently, identifying molecular biomarkers with prognostic significance and revealing the role of MSI in COAD is important for addressing key obstacles in the available treatments.MethodsCIBERSORT and ESTIMATE analyses were performed to evaluate immune infiltration in COAD samples, followed by correlation analysis for MSI and immune infiltration. Then, differentially expressed genes (DEGs) in MSI and microsatellite stability (MSS) samples were identified and subjected to weighted gene co-expression network analysis (WGCNA). A prognostic model was established with univariate cox regression and LASSO analyses, then evaluated with Kaplan-Meier analysis. The correlation between the prognostic model and immune checkpoint inhibitor (ICI) response was also analyzed.ResultsIn total, 701 significant DEGs related to MSI status were identified, and WGCNA revealed two modules associated with the immune score. Then, a seven-gene prognostic model was constructed using LASSO and univariate cox regression analyses to predict survival and ICI response. The high-risk score patients in TCGA and GEO cohorts presented a poor prognosis, as well as a high immune checkpoint expression, so they are more likely to benefit from ICI treatment.ConclusionThe seven-gene prognostic model constructed could predict the survival of COAD and ICI response and serve as a reference for immunotherapy decisions.
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