CD63 + tumor-associated macrophages drive the progression of hepatocellular carcinoma through the induction of epithelial-mesenchymal transition and lipid reprogramming.

BACKGROUND: Tumor-associated macrophages (TAMs) constitute a substantial part of human hepatocellular carcinoma (HCC). The present study was devised to explore TAM diversity and their roles in HCC progression. METHODS: Through the integration of multiple 10 × single-cell transcriptomic data derived from HCC samples and the use of consensus nonnegative matrix factorization (an unsupervised clustering algorithm), TAM molecular subtypes and expression programs were evaluated in detail. The roles played by these TAM subtypes in HCC were further probed through pseudotime, enrichment, and intercellular communication analyses. Lastly, vitro experiments were performed to validate the relationship between CD63, which is an inflammatory TAM expression program marker, and tumor cell lines. RESULTS: We found that the inflammatory expression program in TAMs had a more obvious interaction with HCC cells, and CD63, as a marker gene of the inflammatory expression program, was associated with poor prognosis of HCC patients. Both bulk RNA-seq and vitro experiments confirmed that higher TAM CD63 expression was associated with the growth of HCC cells as well as their epithelial-mesenchymal transition, metastasis, invasion, and the reprogramming of lipid metabolism. CONCLUSIONS: These analyses revealed that the TAM inflammatory expression program in HCC is closely associated with malignant tumor cells, with the hub gene CD63 thus representing an ideal target for therapeutic intervention in this cancer type.

Multi-omic analysis tools for microbial metabolites prediction.

How to resolve the metabolic dark matter of microorganisms has long been a challenging problem in discovering active molecules. Diverse omics tools have been developed to guide the discovery and characterization of various microbial metabolites, which make it gradually possible to predict the overall metabolites for individual strains. The combinations of multi-omic analysis tools effectively compensates for the shortcomings of current studies that focus only on single omics or a broad class of metabolites. In this review, we systematically update, categorize and sort out different analysis tools for microbial metabolites prediction in the last five years to appeal for the multi-omic combination on the understanding of the metabolic nature of microbes. First, we provide the general survey on different updated prediction databases, webservers, or software that based on genomics, transcriptomics, proteomics, and metabolomics, respectively. Then, we discuss the essentiality on the integration of multi-omics data to predict metabolites of different microbial strains and communities, as well as stressing the combination of other techniques, such as systems biology methods and data-driven algorithms. Finally, we identify key challenges and trends in developing multi-omic analysis tools for more comprehensive prediction on diverse microbial metabolites that contribute to human health and disease treatment.

SLC25A19 is a novel prognostic biomarker related to immune invasion and ferroptosis in HCC.

SLC25A19 is a mitochondrial thiamine pyrophosphate (TPP) carrier that mediates TPP entry into the mitochondria. SLC25A19 has been recognized to play a crucial role in many metabolic diseases, but its role in cancer has not been clearly reported. Based on clinical data from The Cancer Genome Atlas (TCGA), the following parameters were analyzed among HCC patients: SLC25A19 expression, enrichment analyses, immune infiltration, ferroptosis and prognosis analyses. In vitro, the SLC25A19 high expression was validated by qRT-PCR and Immunohistochemistry. Subsequently, a series of cell function experiments, including CCK8, EdU, clone formation, trans-well and scratch assays, were conducted to illustrate the effect of SLC25A19 on the growth and metastasis of cancer cells. Meanwhile, indicators related to ferroptosis were also detected. SCL25A19 is highly expressed in HCC and predicts a poor prognosis. Elevated SLC25A19 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Our results indicate that SLC25A19 has a generally good prognosis predictive and diagnostic ability. The results of gene enrichment analyses showed that SLC25A19 is significantly correlated with immune infiltration, fatty acid metabolism, and ferroptosis marker genes. In vitro experiments have confirmed that silencing SLC25A19 can significantly inhibit the proliferation and migration ability of cancer cells and induce ferroptosis in HCC. In conclusion, these findings indicate that SLC25A19 is novel prognostic biomarker related to immune invasion and ferroptosis in HCC, and it is an excellent candidate for therapeutic target against HCC.

Tumor extrachromosomal DNA: Biogenesis and recent advances in the field.

Extrachromosomal DNA (ecDNA) is a self-replicating circular DNA originating from the chromosomal genome and exists outside the chromosome. It contains specific gene sequences and non-coding regions that regulate transcription. Recent studies have demonstrated that ecDNA is present in various malignant tumors. Malignant tumor development and poor prognosis may depend on ecDNA's distinctive ring structure, which assists in amplifying oncogenes. During cell division, an uneven distribution of ecDNA significantly enhances tumor cells' heterogeneity, allowing tumor cells to adapt to changes in the tumor microenvironment and making them more resistant to treatments. The application of ecDNA as a cancer biomarker and therapeutic target holds great potential. This article examines the latest advancements in this area and discusses the potential clinical applications of ecDNA.

Association between the oxidative balance score and thyroid function: Results from the NHANES 2007-2012 and Mendelian randomization study.

BACKGROUND: Oxidative stress is a significant contributor to the development of various diseases, and the oxidative balance score (OBS) is a valuable tool for assessing the impact of dietary and lifestyle factors on oxidative stress in humans. Nevertheless, the precise relationship between OBS and thyroid function in adults remains elusive. METHODS: This cross-sectional study comprised 6222 adult participants drawn from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012. Employing weighted multivariable linear regression modeling, the study estimated the connection between OBS quartiles and thyroid functions. The causal relationship between OBS components and thyroid function was analyzed by Mendelian randomization (MR). RESULTS: We found a significant negative correlation between OBS and free thyroxine (FT4) and total thyroxine (TT4). Univariate and multivariate MR Analyses showed a causal relationship between BMI and FT4. Copper, smoking, and riboflavin showed a causal relationship with FT4 after moderation. CONCLUSION: We found that a lifestyle high in antioxidant exposure reduced FT4 and TT4 levels in the population. We suggest that BMI, Copper, and Riboflavin are important factors in the regulation of FT4 levels.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

RPL35A promotes the progression of cholangiocarcinoma by mediating HSPA8 ubiquitination.

BACKGROUND: Cholangiocarcinoma (CCA) is a biliary epithelial malignant tumor with an increasing incidence worldwide. Therefore, further understanding of the molecular mechanisms of CCA progression is required to identify new therapeutic targets. METHODS: The expression of RPL35A in CCA and para-carcinoma tissues was detected by immunohistochemical staining. IP-MS combined with Co-IP identified downstream proteins regulated by RPL35A. Western blot and Co-IP of CHX or MG-132 treated CCA cells were used to verify the regulation of HSPA8 protein by RPL35A. Cell experiments and subcutaneous tumorigenesis experiments in nude mice were performed to evaluate the effects of RPL35A and HSPA8 on the proliferation, apoptosis, cell cycle, migration of CCA cells and tumor growth in vivo. RESULTS: RPL35A was significantly upregulated in CCA tissues and cells. RPL35A knockdown inhibited the proliferation and migration of HCCC-9810 and HUCCT1 cells, induced apoptosis, and arrested the cell cycle in G1 phase. HSPA8 was a downstream protein of RPL35A and overexpressed in CCA. RPL35A knockdown impaired HSPA8 protein stability and increased HSPA8 protein ubiquitination levels. RPL35A overexpression promoted CCA cell proliferation and migration. HSPA8 knockdown inhibited CCA cell proliferation and migration, and reversed the promoting effect of RPL35A. Furthermore, RPL35A promoted tumor growth in vivo. In contrast, HSPA8 knockdown suppressed tumor growth, while was able to restore the effects of RPL35A overexpression. CONCLUSION: RPL35A was upregulated in CCA tissues and promoted the progression of CCA by mediating HSPA8 ubiquitination.

Lysine acetyltransferase 6A maintains CD4+ T cell response via epigenetic reprogramming of glucose metabolism in autoimmunity.

Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.

Study on quality analysis of different species of Coptidis rhizome based on fingerprint-effect relationship.

INTRODUCTION: The quality evaluation of Coptidis rhizome (CR) is attributed to the origin and processing method, and this strategy of ignoring the bioactive components usually leads to biased quality analysis, which is difficult to indicate the clinical efficacy. OBJECTIVES: In order to evaluate the quality level of different species of CR, we collected 20 batches of CR and investigated the fingerprint-effect relationship. METHODS: High-performance liquid chromatography (HPLC) fingerprints of CR were established, and the fingerprint-effect relationship was explored using cluster analysis, principal component analysis, Pearson correlation analysis, grey relation analysis, and partial least squares regression. RESULTS: We have identified a total of 10 common peaks (1-10) with similarity scores above 0.96. The study on the relationship between spectra and potency further showed that the contents of peaks 8, 9, and 10 are potential key components. And based on a previous study, a method of one measurement and multiple evaluations of CR was established to achieve the goal of simplifying the analytical process and reducing costs. CONCLUSION: Through a combination of fingerprint analysis, antioxidant activity evaluation, fingerprint-efficacy relationship analysis, and simultaneous quantification of multiple components, a CR quality control index and method have been selected and established, which can also provide a more comprehensive quality evaluation for traditional Chinese medicine.

All-natural chitosan-based polyimine vitrimer with multiple advantages: A novel strategy to solve nondegradable plastic waste pollution.

The increasing amount of nondegradable petroleum-based plastic waste releases chemical hazards, posing a significant threat to the environment and human health. Chitosan, derived from marine wastes, is an attractive feedstock for the preparation of plastic replacement due to its renewable and degradable nature. However, in most cases, complex chemical modifications of chitosan or hybridization with chemicals from fossil resources are required. Herein, we present a high-performance chitosan-based polyimine vitrimer (CS-PI) through a mild and catalyst-free Schiff base reaction between chitosan and vanillin. The CS-PI were formed by integrating dynamic imine bonds into the polymer networks, resulting in superior thermo-processability and mechanical performances. The tensile strength and Young's modulus of the CS-PI films reached 38.72 MPa and 3.20 GPa, respectively, which was significantly higher than that of both commercial petroleum-based plastics and bioplastics. Additionally, the CS-PI films exhibited good light transmittance, self-healing ability, reprocess capacity, water resistance, and durability to various organic solvents. Moreover, the CS-PI films could be completely degraded under both acidic and natural conditions, enabling a sustainable circulation. Therefore, this work offers a new design strategy for developing all-natural environmentally friendly polymers as sustainable replacements for petroleum-based plastics, thus reducing the accumulation of nondegradable plastic waste.

Association between the dietary inflammatory index and gout in the National Health and Nutrition Examination Survey 2007-2018.

Objective: The aim of our study was to investigate whether the Dietary Inflammatory Index (DII) correlated with gout in American adults. Method: The study used data from the 2007-2018 National Health and Nutrition Examination Survey, with 27,710 adults participating. Initially, multivariable analysis was performed, with controls for covariates, to assess the link of DII and gout. Then, restricted cubic splines (RCS) were applied to model the nonlinear relationship of DII and gout. Furthermore, propensity score matching (PSM) as a further study of potential relationships was established. Eventually, subgroup analysis was performed. Result: Participants within the highest DII quartile would be more susceptible to increased risk of gout in the univariate regression model (Q4 vs. Q1, OR = 1.31, CI: 1.05-1.63). Additionally, a positive correlation was detected between gout risk and DII after adjusting on drinking, smoking, gender, race, age, and BMI. Based on RCS analysis, we observed that the risk of gout raised sharply as DII values increased, then flattened, and increased sharply again when the DII was greater than approximately 2.5. After performing the PSM, it was observed that DII correlated in a positive way to the presence of gout on a fully adjusted multivariable model. Subgroup analysis revealed that the link of DII and gout showed no statistical significance in females, blacks, Mexicans, nor in the population that smoked. Conclusion: Greater degrees of pro-inflammation correlate with a higher risk of gout and might be a predisposing factor for gout. Hence, tactics fostering an anti-inflammatory diet for preventing and improving gout in adults should be regarded.

Asymmetric Synthesis of Bulky N-Cyclopropylmethyl-1-aryl-1-phenylmethylamines Catalyzed by Engineered Imine Reductases.

Enzymatic reduction of diphenylmethanimine derivatives has rarely been reported owing to their steric hindrance. Herein, imine reductase (IRED) from Nocardia cyriacigeorgica rationally engineered with an efficient strategy of focused rational iterative site-specific mutagenesis (FRISM) was selected for the reduction of a series of N-cyclopropylmethyl-1-aryl-1-phenylmethylimines. Two highly enantioselective IRED variants were identified, providing various bulky amine products with moderate to high yields and high ee values (up to >99%). This work provided an effective method to construct these important pharmaceutical intermediates.

Comparison of the efficacy and safety between rivaroxaban and dabigatran in the treatment of acute portal vein thrombosis in cirrhosis.

BACKGROUND: New oral anticoagulants (NOACs) have been becoming prevalent in recent years and are increasingly used in the treatment of port vein thrombosis. The difference of the efficacy and safety between rivaroxaban and dabigatran remains unclear in the treatment of cirrhotic patients with acute portal vein thrombosis (PVT). METHODS: This retrospective study included all consecutive cirrhotic patients with acute portal vein thrombosis in our institute from January 2020 to December 2021. The patients received oral anticoagulation with rivaroxaban or dabigatran. The demographic, clinical, and imaging data of patients were collected. The diagnosis of acute PVT was confirmed by imaging examinations. The severity of liver cirrhosis was assessed using Child-Pugh score and Model for End-Stage Liver Disease (MELD) score. Outcomes included recanalization (complete, partial, and persistent occlusion), liver function, bleedings, and survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. The Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: A total of 94 patients were included, 52 patients (55%) received rivaroxaban and 42 (45%) with dabigatran. The complete and partial recanalization of PVT was observed in 41 patients. There was no significant difference in complete recanalization, partial recanalization, and persistent occlusion between the two groups. With multivariate analysis, D-dimer (HR 1.165, 95% CI 1.036-1.311, p = 0.011) was independent predictors of complete recanalization. The Child-Pugh score (p = 0.001) was significantly improved in both two groups after anticoagulation, respectively. However, there was no difference between the two groups. The probability of survival was 94%, 95% in the rivaroxaban and dabigatran groups (log-rank p = 0.830). Major bleedings were reported in 3 patients (6%) in rivaroxaban group and 1 patient (2%) in dabigatran group (p = 0.646). Six patients (12%) in rivaroxaban group experienced minor bleeding, and five (12%) from dabigatran group (p = 0.691). CONCLUSIONS: The efficacy and safety were comparable between rivaroxaban and dabigatran in the treatment of cirrhotic patients with acute portal vein thrombosis. And D-dimer can contribute to the prediction of PVT recanalization in cirrhotic patients.

An Autophagy-Associated MITF-GAS5-miR-23 Loop Attenuates Vascular Oxidative and Inflammatory Damage in Sepsis.

BACKGROUND: Sepsis induces GAS5 expression in the vascular endothelium, but the molecular mechanism is unclear, as is the role of GAS5 in sepsis. METHODS AND RESULTS: We observed that GAS5 expression in the endothelium was significantly upregulated in a sepsis mouse model. ChIP-PCR and EMSA confirmed that the oxidative stress (OS)-activated MiT-TFE transcription factor (MITF, TFE3, and TFEB)-mediated GAS5 transcription. In vitro, GAS5 overexpression attenuated OS and inflammation in endothelial cells (ECs) while maintaining the structural and functional integrity of mitochondria. In vivo, GAS5 reduced tissue ROS levels, maintained vascular barrier function to reduce leakage, and ultimately attenuated sepsis-induced lung injury. Luciferase reporter assays revealed that GAS5 protected MITF from degradation by sponging miR-23, thereby forming a positive feedback loop consisting of MITF, GAS5, and miR-23. Despite the fact that the OS-activated MITF-GAS5-miR-23 loop boosted MITF-mediated p62 transcription, ECs do not need to increase mitophagy to exert mitochondrial quality control since MITF-mediated Nrf2 transcription exists. Compared to mitophagy, MITF-transcribed p62 prefers to facilitate the autophagic degradation of Keap1 through a direct interaction, thereby relieving the inhibition of Nrf2 by Keap1, indicating that MITF can upregulate Nrf2 at both the transcriptional and posttranscriptional levels. Following this, ChIP-PCR demonstrated that Nrf2 can also transcribe MITF, revealing that there is a reciprocal positive regulatory association between MITF and Nrf2. CONCLUSION: In sepsis, the ROS-activated MITF-GAS5-miR-23 loop integrated the antioxidant and autophagy systems through MITF-mediated transcription of Nrf2 and p62, which dynamically regulate the level and type of autophagy, as well as exert antioxidant and anti-inflammatory effects.

Identification of basement membrane-related prognostic signature for predicting prognosis, immune response and potential drug prediction in papillary renal cell carcinoma.

Papillary renal cell carcinoma (PRCC) is a malignant neoplasm of the kidney and is highly interesting due to its increasing incidence. Many studies have shown that the basement membrane (BM) plays an important role in the development of cancer, and structural and functional changes in the BM can be observed in most renal lesions. However, the role of BM in the malignant progression of PRCC and its impact on prognosis has not been fully studied. Therefore, this study aimed to explore the functional and prognostic value of basement membrane-associated genes (BMs) in PRCC patients. We identified differentially expressed BMs between PRCC tumor samples and normal tissue and systematically explored the relevance of BMs to immune infiltration. Moreover, we constructed a risk signature based on these differentially expressed genes (DEGs) using Lasso regression analysis and demonstrated their independence using Cox regression analysis. Finally, we predicted 9 small molecule drugs with the potential to treat PRCC and compared the differences in sensitivity to commonly used chemotherapeutic agents between high and low-risk groups to better target patients for more precise treatment planning. Taken together, our study suggested that BMs might play a crucial role in the development of PRCC, and these results might provide new insights into the treatment of PRCC.

A Biodegradable, Waterproof, and Thermally Processable Cellulosic Bioplastic Enabled by Dynamic Covalent Modification.

The growing environmental concern over petrochemical-based plastics continuously promotes the exploration of green and sustainable substitute materials. Compared with petrochemical products, cellulose has overwhelming superiority in terms of availability, cost, and biodegradability; however, cellulose's dense hydrogen-bonding network and highly ordered crystalline structure make it hard to be thermoformed. A strategy to realize the partial disassociation of hydrogen bonds in cellulose and the reassembly of cellulose chains via constructing a dynamic covalent network, thereby endowing cellulose with thermal processability as indicated by the observation of a moderate glass transition temperature (Tg  = 240 °C), is proposed. Moreover, the cellulosic bioplastic delivers a high tensile strength of 67 MPa, as well as excellent moisture and solvent resistance, good recyclability, and biodegradability in nature. With these advantageous features, the developed cellulosic bioplastic represents a promising alternative to traditional plastics.

Landscapes and mechanisms of CD8+ T cell exhaustion in gastrointestinal cancer.

CD8+ T cells, a cytotoxic T lymphocyte, are a key component of the tumor immune system, but they enter a hyporeactive T cell state in long-term chronic inflammation, and how to rescue this depleted state is a key direction of research. Current studies on CD8+ T cell exhaustion have found that the mechanisms responsible for their heterogeneity and differential kinetics may be closely related to transcription factors and epigenetic regulation, which may serve as biomarkers and potential immunotherapeutic targets to guide treatment. Although the importance of T cell exhaustion in tumor immunotherapy cannot be overstated, studies have pointed out that gastric cancer tissues have a better anti-tumor T cell composition compared to other cancer tissues, which may indicate that gastrointestinal cancers have more promising prospects for the development of precision-targeted immunotherapy. Therefore, the present study will focus on the mechanisms involved in the development of CD8+ T cell exhaustion, and then review the landscapes and mechanisms of T cell exhaustion in gastrointestinal cancer as well as clinical applications, which will provide a clear vision for the development of future immunotherapies.

CCND1-Induced Autophagy Contributes to Lymph Node Metastasis in Endometrial Cancer.

Endometrial cancer with lymph node metastasis shows poor prognosis, while the biomarker to predict the metastasis is lacking. The relative mRNA or protein expression of cyclin D1 (CCND1) and autophagy-related molecules were detected in real-time PCR and Western blot. Correlation analysis was applied to identify any significant patterns, and receiver operating characteristics (ROC) was performed to assess the prediction value. CCND1 vector was transfected in Ishikawa (ISK) cells, and the relative expression of autophagy-related molecules was detected with Western blot. CCND1 was overexpressed in endometrial cancer and correlated with lymph node metastasis. ROC analysis found that CCND1 had a predictive value to discriminate tumors from normal tissues (cut off=1.455; sensitivity, 71%; specificity, 84%; area under curve (AUC) 0.82; p<0.001) and had a predictive value to indicate metastasis (cut off=1.871; sensitivity, 54.17%; specificity, 75%; AUC 0.674; p=0.003). Increased BECLIN1 (r=0.39, p<0.001) and ATG5 (r=0.41, p<0.001) expression were positively correlated to CCND1. On the other hand, the relative protein expression of CCND1, BECLIN1, ATG5, ATG7, and LC3 I/II were also increased in tumor tissues. CCND1 overexpressed ISK cells showed upregulated BECLIN1, ATG5, ATG7, and LC3 I/II expression. CCND1 promoted autophagy may contribute to lymph node metastasis in endometrial cancer.

Cell division cycle-associated 8 is a prognostic biomarker related to immune invasion in hepatocellular carcinoma.

BACKGROUND: Cell division cycle-associated 8 (CDCA8) is involved in numerous signaling networks, and it serves a crucial modulatory function in multiple malignant tumors. However, its significance in prognosis and immune infiltration in hepatocellular carcinoma (HCC) remains unclear. MATERIALS AND METHODS: Herein, we examined the CDCA8 levels in tumor tissues, as well as its associated signaling pathways and correlation with immune infiltration. Additionally, we further clarified the prognostic significance of CDCA8 among HCC patients. HCC patient information was recruited from The Cancer Genome Atlas (TCGA). Using bioinformatics, the following parameters were analyzed among HCC patients: CDCA8 expression, enrichment analysis, immune infiltration, and prognosis analysis. Moreover, we employed in vitro investigations, such as, qRT-PCR, immunohistochemistry (IHC), and cell functional experiments to validate our results. RESULTS: Elevated CDCA8 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Elevated CDCA8 expression HCC patients exhibited reduced overall survival (OS) (p < 0.001), disease-specific survival (DSS) (p < 0.001), and progress free interval (PFI) H(p < 0.001). According to the ROC analysis, the area under the curve (AUC) was 0.997. Multivariate analysis revealed that CDCA8 was a stand-alone prognostic indicator of patient OS (p = 0.009) and DSS (p = 0.006). A nomogram was then generated based on the multivariate analysis, and the C-indexes and calibration chart revealed excellent predictive performance in determining HCC patient outcome. Based on the GSEA analysis, CDCA8 modulated the P53, Notch, PPAR, E2F networks. We observed a direct link between CDCA8 levels and Th2 and T helper cells, and a negative link between CDCA8 levels and dendritic cells (DC), neutrophils, cytotoxic cells, and CD8 T cells. Furthermore, CDCA8 deficiency inhibited liver cancer cell proliferation and invasion. CONCLUSION: In conclusion, these findings indicate that CDCA8 is a new molecular bioindicator of HCC patient prognosis, and it is an excellent candidate for therapeutic target against HCC.