The Systemic Immune Inflammation Index (SII) Combined with the Creatinine-to-Cystatin C Ratio (Cre/CysC) Predicts Sarcopenia in Patients with Liver Cirrhosis Complicated with Primary Hepatocellular Carcinoma.

BACKGROUND: Sarcopenia is a risk factor for poor cancer prognosis. Early identification and timely intervention of sarcopenia can improve patient prognosis. METHODS: A total of 91 patients with liver cirrhosis complicated with primary hepatocellular carcinoma were retrospectively analyzed. Based on the results of multivariable logistic regression analysis, a nomogram was developed. Moreover, 50 patients were enrolled for external validation. The predictive efficacy of the nomogram was evaluated using the receiver operating characteristic curve (ROC). RESULTS: According to the logistic regression analysis results, age, body mass index (BMI), creatinine-to-cystatin C ratio (Cre/CysC), and systemic immune inflammation index (SII) were independent risk factors of sarcopenia in patients with cirrhosis complicated with primary hepatocellular carcinoma (HCC) (all p < 0.05). The ABCS nomogram model was established, and the area under the ROC curve (AUC) was 0.896 (84.7% sensitivity, 81.2% specificity). The calibration curve of the nomogram was close to the ideal diagonal line. The predictive efficacy of the nomogram was verified through the external validation. CONCLUSION: The ABCS model based on SII and Cre/CysC can be used to identify high-risk sarcopenia in patients with cirrhosis complicated with HCC in the early stage.

Image Registration for Visualizing Magnetic Flux Leakage Testing under Different Orientations of Magnetization.

The Magnetic Flux Leakage (MFL) visualization technique is widely used in the surface defect inspection of ferromagnetic materials. However, the information of the images detected through the MFL method is incomplete when the defect (especially for the cracks) is complex, and some information would be lost when magnetized unidirectionally. Then, the multidirectional magnetization method is proposed to fuse the images detected under different magnetization orientations. It causes a critical problem: the existing image registration methods cannot be applied to align the images because the images are different when detected under different magnetization orientations. This study presents a novel image registration method for MFL visualization to solve this problem. In order to evaluate the registration, and to fuse the information detected in different directions, the mutual information between the reference image and the MFL image calculated by the forward model is designed as a measure. Furthermore, Particle Swarm Optimization (PSO) is used to optimize the registration process. The comparative experimental results demonstrate that this method has a higher registration accuracy for the MFL images of complex cracks than the existing methods.

Decreased expression of HADH is related to poor prognosis and immune infiltration in kidney renal clear cell carcinoma.

Kidney renal clear cell carcinoma (KIRC) is the subtype pf kidney cancer having the highest mortality as well as the highest potential of invasion and metastasis. The expression of HADH, encoding a key enzyme in fatty acid ß-oxidation, has rarely been reported to correlate with prognosis and immune infiltration in cancers. This study aimed to explore the prognostic value of HADH in patients with KIRC. Gene expression profiles and clinical data of KIRC patients were acquired from The Cancer Genome Atlas. We compared the expression of HADH between KIRC tissues and normal tissues. Then, the relationship between HADH expression and the clinicopathological characteristics (survival, age, gender, stage, and grade) of KIRC was explored. Data from several online databases and paraffin-embedded specimens from two cohorts were used for external validation (10 cases from Meizhou People's Hospital and another 75 cases from a tissue chip, with both cohorts including KIRC samples and paired normal tissues). We also predicted the fractions of tumor-infiltrating immune cells (TIICs) in various tissues using CIBERSORT. Next, we estimated the prognostic value of differences in TIIC proportions between the high and low HADH expression groups. Finally, gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms by which HADH expression influences patient survival. The expression of HADH was significantly lower in KIRC tissue than in normal tissue. Decreased expression of HADH was significantly correlated with high histologic grade, advanced stage, and poor prognosis. The differential expression of HADH was validated at the protein level by immunohistochemistry. Multivariate Cox regression analysis indicated that HADH was an independent prognostic factor for KIRC. In addition, HADH expression was significantly associated with the accumulation of several TIICs, especially regulatory T cells. Finally, GSEA revealed that the transcriptome of the low HADH expression group was significantly enriched in genes involved in not only epithelial-mesenchymal transition and inflammatory response but also TNF-α, IL-6-JAK-STAT3, and interferon-γ signaling. In conclusion, our study demonstrated that decreased expression of HADH is related to poor prognosis and immune infiltration in KIRC; this finding may provide crucial information for the development of immunotherapies.

Revealing the characteristics of SETD2-mutated clear cell renal cell carcinoma through tumor heterogeneity analysis.

Background: Renal cell carcinoma (RCC) is the most prevalent type of malignant kidney tumor in adults, with clear cell renal cell carcinoma (ccRCC) comprising about 75% of all cases. The SETD2 gene, which is involved in the modification of histone proteins, is often found to have alterations in ccRCC. Yet, our understanding of how these SETD2 mutations affect ccRCC characteristics and behavior within the tumor microenvironment is still not fully understood. Methods: We conducted a detailed analysis of single-cell RNA sequencing (scRNA-seq) data from ccRCC. First, the data was preprocessed using the Python package, "scanpy." High variability genes were pinpointed through Pearson's correlation coefficient. Dimensionality reduction and clustering identification were performed using Principal Component Analysis (PCA) and the Leiden algorithm. Malignant cell identification was conducted with the "InferCNV" R package, while cell trajectories and intercellular communication were depicted using the Python packages "VIA" and "cellphoneDB." We then employed the R package "Deseq2" to determine differentially expressed genes (DEGs) between groups. Using high-dimensional weighted gene correlation network analysis (hdWGCNA), co-expression modules were identified. We intersected these modules with DEGs to establish prognostic models through univariate Cox and the least absolute shrinkage and selection operator (LASSO) method. Results: We identified 69 and 53 distinctive cell clusters, respectively. These were classified further into 12 unique cell types. This analysis highlighted the presence of an abnormal tumor sub-cluster (MT + group), identified by high mitochondrial-encoded protein gene expression and an indication of unfavorable prognosis. Investigation of cellular interactions spotlighted significant interactions between the MT + group and endothelial cells, macrophaes. In addition, we developed a prognostic model based on six characteristic genes. Notably, risk scores derived from these genes correlated significantly with various clinical features. Finally, a nomogram model was established to facilitate more accurate outcome prediction, incorporating four independent risk factors. Conclusion: Our findings provide insight into the crucial transcriptomic characteristics of ccRCC associated with SETD2 mutation. We discovered that this mutation-induced subcluster could stimulate M2 polarization in macrophages, suggesting a heightened propensity for metastasis. Moreover, our prognostic model demonstrated effectiveness in forecasting overall survival for ccRCC patients, thus presenting a valuable clinical tool.

Association between milk consumption and kidney stones in U.S. adults: results from NHANES 2007-2018.

Background: Dietary strategies play a crucial role in the prevention of kidney stones. While milk is known for its rich nutritional content, its impact on kidney stone formation remains unclear. This study aimed to examine the relationship between milk consumption and the risk of kidney stones among U.S. adults. Methods: We included 24,620 participants aged 20 and older from the National Health and Nutrition Examination Survey (2007-2018). Milk consumption was defined based on each participant's response to the questionnaire item on "Past 30 day milk product consumption." Kidney stones history was self-reported by participants. The analysis employed weighted multivariate logistic regression models, followed by subgroup analyses for result validation, and explored the age-related dynamics of milk consumption's effect on kidney stone risk using a restricted cubic spline model. Results: Adjusted findings revealed that higher milk intake was associated with a decreased risk of kidney stones (odds ratio [OR] = 0.90, 95% confidence interval [CI] 0.85-0.96), notably among women (OR = 0.86, 95% CI 0.80-0.92) but not significantly in men (OR = 0.94, 95% CI 0.86-1.02). Smoothed curves across all ages showed that women consuming milk had a lower incidence of kidney stones than those who did not, particularly with regular consumption. Conclusion: This study uncovered that across all age groups, higher frequency of milk consumption in women is associated with a reduced risk of kidney stones. However, further prospective cohort studies are needed to confirm this finding.

BIRC6 Modulates the Protein Stability of Axin to Regulate the Growth, Stemness, and Resistance of Renal Cancer Cells via the ß-Catenin Pathway.

The mechanism underlying the development of renal cell carcinoma (RCC) remains unclear, and effective prevention and therapeutic measures are lacking. BIRC6, a protein inhibitor of apoptosis, has attracted great interest. Our data indicated that overexpression of BIRC6 elevated cell growth, colony formation, migration, and invasion of cultured RCC cells, while siRNA knockdown of BIRC6 suppressed these processes. Additionally, BIRC6 was highly expressed in RCC clinical samples along with a downregulated level of Axin. Immunoprecipitation assays found that BIRC6 interacted with Axin and the two proteins colocalized within the cytoplasm of RCC cells. Overexpression of BIRC6 promoted the ubiquitination modification of Axin, while genetic knockdown of BIRC6 suppressed it. Furthermore, overexpression of BIRC6 significantly promoted the turnover of Axin, suggesting BIRC6's inhibitory effect on Axin protein stability. BIRC6 was also upregulated in cancer stem-like cells of RCC and increased the drug resistance of RCC cells against sunitinib. Western blotting assays showed that the overexpression of BIRC6 upregulated CXCR4 protein expression and activated the ß-catenin pathway. Two cell lines were then constructed with BIRC6 overexpressed by lentiviruses. Pharmacological administration of a Wnt/ß-catenin inhibitor, XAV-939, or genetic knockdown of ß-catenin inhibited cell growth, tumor sphere formation, colony formation, migration, and invasion of BIRC6-overexpressed cells. In vivo administration of XAV-939 markedly suppressed the tumorigenesis of BIRC6-overexpressed RCC cells in nude mice. In conclusion, we propose that BIRC6 activates the ß-catenin signaling pathway via mediating the ubiquitination and degradation of Axin, promoting the growth, stemness, and drug resistance of RCC cells. This project aims to elucidate the role of BIRC6 as a potential therapeutic target and provide new insights into the clinical treatment of RCC.

Postharvest Physiology and Handling of Guava Fruit.

Guavas are typical tropical fruit with high nutritional and commercial value. Because of their thin skin and high metabolic rate, guavas are highly susceptible to water loss, physical damage, and spoilage, severely limiting their shelf-life. Guavas can typically only be stored for approximately one week at room temperature, making transportation, storage, and handling difficult, resulting in low profit margins in the industry. This review focuses on the physiological and biochemical changes and their molecular mechanisms which occur in postharvest guavas, and summarizes the various management strategies for extending the shelf-life of these sensitive fruits by means of physical and chemical preservation and their combinations. This review also suggests future directions and reference ideas for the development of safe and efficient shelf-life extension techniques.

PD-L1 expression and its correlation with tumor biomarkers in Chinese urothelial bladder cancer.

Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P < 0.001) and between IC with membrane PD-L1 positivity and CD8+ T cells (0.44; P < 0.001). There is high prevalence of PD-L1 expression in Chinese patients with MIUBC, suggesting that a sizable subset of patients could benefit from immunotherapy. The correlation of PD-L1 expression with tumor biomarkers provide clues for mechanisms underlying the effects of biomarkers for predicting efficacy.

Real-world effectiveness and safety of goserelin 10.8-mg depot in Chinese patients with localized or locally advanced prostate cancer.

OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.

Low OGDHL expression affects the prognosis and immune infiltration of kidney renal clear cell carcinoma.

Background: Oxoglutarate dehydrogenase-like (OGDHL) modulates glutamine metabolism to influence tumor progression. Therefore, we aimed to explore the potential role of OGDHL in the prognosis of kidney renal clear cell carcinoma (KIRC) and its effect on immune infiltration. Methods: The Cancer Genome Atlas, Tumor Immune Estimation Resource, Gene Expression Profiling Interactive Analysis, Human Protein Atlas, and The University of Alabama at Birmingham Cancer databases and the GSE53757 dataset were utilized to analyze expression difference and prognosis of OGDHL in tumor and normal tissue; diagnostic value was assessed using receiver operating characteristic curves. Correlations with clinical features and survival prognosis were analyzed. Independent prognostic factors were identified using univariate and multifactorial Cox regression analysis. We used the CIBERSORT analysis tool to discover the proportion of tumor-infiltrating immune cells (TIICs) in KIRC patients. Next, the differences in the proportion of TIICs under different OGDHL expression were analyzed. Finally, we explored the potential mechanisms by which OGDHL expression affects patient survival using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). Results: OGDHL expression was markedly downregulated in KIRC tissues compared to in normal tissues, and the downregulation of OGDHL expression was significantly associated with tumor progression (including tumor stage and grade) and poor prognosis. Cox regression analyses revealed OGDHL to be an independent prognostic factor for KIRC. CIBERSORT analysis showed that OGDHL expression is associated with differences in the proportion of several TIICs, particularly resting mast cells. Finally, GO and KEGG analysis showed that OGDHL was associated with extracellular matrix and epithelial cell differentiation involved in kidney development. GSEA indicated that low OGDHL was closely related to the activation of carcinogenic signaling pathways, including epithelial mesenchymal transition, tumor necrosis factor alpha and nuclear factor kappa B signaling pathway, negative regulation of apoptotic signaling, collagen formation, etc. Conclusions: OGDHL level can be monitored for diagnosing KIRC. Reduced expression is associated with poor prognosis and immune infiltration of KIRC. OGDHL is expected to become a new target for the treatment of KIRC.

Construction and validation of cuproptosis-related lncRNA prediction signature for bladder cancer and immune infiltration analysis.

Bladder cancer (BC) is a common urologic tumor with a high recurrence rate. Cuproptosis and long noncoding RNAs (lncRNAs) have demonstrated essential roles in the tumorigenesis of many malignancies. Nevertheless, the prognostic value of cuproptosis-related lncRNA (CRLs) in BC is still unclear. The public data used for this study were acquired from the Cancer Genome Atlas database. A comprehensive exploration of the expression profile, mutation, co-expression, and enrichment analyses of cuproptosis-related genes was performed. A total of 466 CRLs were identified using Pearson's correlation analysis. 16 prognostic CRLs were then retained by univariate Cox regression. Unsupervised clustering divided the patients into two clusters with diverse survival outcomes. The signature consists of 7 CRLs was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Survival curves and receiver operating characteristics showed the prognostic signature possessed good predictive value, which was validated in the testing and entire sets. The reliability and stability of our signature were further confirmed by stratified analysis. Additionally, the signature-based risk score was confirmed as an independent prognostic factor. Gene set enrichment analysis showed molecular alteration in the high-risk group was closely associated with cancer. We then developed the clinical nomogram using independent prognostic indicators. Notably, the infiltration of immune cells and expression of immune checkpoints were higher in the high-risk group, suggesting that they may benefit more from immunotherapy. In summary, the prognostic signature might effectively predict the prognosis and provide new insight into the clinical treatment of BC patients.

Synchrony makes neurons fire in sequence, and stimulus properties determine who is ahead.

The synchronized activity of cortical neurons often features spike delays of several milliseconds. Usually, these delays are considered too small to play a role in cortical computations. Here, we use simultaneous recordings of spiking activity from up to 12 neurons to show that, in the cat visual cortex, the pairwise delays between neurons form a preferred order of spiking, called firing sequence. This sequence spans up to ∼ 15 ms and is referenced not to external events but to the internal cortical activity (e.g., beta/gamma oscillations). Most importantly, the preferred sequence of firing changed consistently as a function of stimulus properties. During beta/gamma oscillations, the reliability of firing sequences increased and approached that of firing rates. This suggests that, in the visual system, short-lived spatiotemporal patterns of spiking defined by consistent delays in synchronized activity occur with sufficient reliability to complement firing rates as a neuronal code.

Epirubicin-loaded beads transarterial prostatic arterial chemoembolization is a promising treatment for advanced prostate cancer with lower urinary tract obstruction or hematuria-a case series report.

Background: Prostatic arterial embolization (PAE) is an effective minimally invasive treatment for lower urinary tract obstruction and hematuria in patients with benign prostatic hyperplasia (BPH). This study was aim to evaluate the safety and short-term efficacy of drug epirubicin-loaded beads transarterial prostatic arterial chemoembolization (DEB-PACE) for the treatment of advanced prostate cancer (PC) with lower urinary tract obstruction or hematuria. Methods: A total of 8 patients with advanced PC undergoing DEB-PACE from August 2020 to February 2022 were retrospectively enrolled. The patients were followed up at 1 week, 1, 3, 6 and 12 months after DEB-PACE. The origin of prostatic arteries, technical success, clinical success rate, duration of the indwelling urinary catheter, International Prostate Symptom Score (IPSS), QoL score (quality of life), prostate volume (PV), prostate-specific antigen (PSA) level and complications were recorded. The short-term efficacy (changes in IPSS, PV and QoL value from baseline to 3 months) were analysed. Results: There were 17 prostatic arteries in 8 patients, which mainly originated from internal pudendal artery (11/17, 64.7%), the technical success rate is 100%. After treatment, the symptoms of lower urethral obstruction in 8 patients were significantly improved that PSA, PV, IPSS and QoL level were significantly reduced. The catheter was successfully removed within 1 week on average, and 2 patients with hematuria disappeared within 5 days. The clinical success rate is 100%. At 1 month postoperatively, mean PV reduction was 30.28±6.963 cm3 (P=0.0457), mean IPSS reduction was 21.13±2.887 points (P=0.0042), mean QoL reduction was 3.75±0.366 points (P=0.006). At 3 months postoperatively, mean PV reduction was 46.14±8.906 cm3 (P=0.0112), mean IPSS reduction was 24.5±2.398 points (P=0.0003), mean QoL reduction was 4.25±0.25 points (P=0.0003). There were no serious complications occurred in all patients. Conclusions: DEB-PACE is a promising treatment for advanced PC with lower urinary tract obstruction or hematuria. However, the efficacy and safety of DEB-PACE for advanced PC is needed to validated by prospective large sample randomized controlled study.

Physiological and transcription analyses reveal regulatory pathways of 6-benzylaminopurine delaying leaf senescence and maintaining quality in postharvest Chinese flowering cabbage.

The regulatory role of cytokinins (CTKs) in leaf senescence has been documented in different species, including Chinese flowering cabbage. However, its physiological and molecular basis relatively remains unknown. In this study, exogenous application of a CTK analogue 6-benzylaminopurine (6-BA) significantly retarded leaf senescence of Chinese flowering cabbage, with less chlorophyll degradation and lower accumulation of reactive oxygen species (ROS) and malondialdehyde compared with the control group. Meanwhile, higher levels of soluble sugars and proteins, flavonoids, cellulose, amino acids, total phenols, procanthocyanins, and vitamin C were retained in 6-BA-treated leaves. 6-BA treatment also prevented the decline in endogenous CTK content and the increase in ethylene, abscisic acid, and jasmonic acid contents. Moreover, the comparative transcriptome analysis revealed that a total of 21,895 differently expressed genes (DEGs) were identified from four comparisons of 6-BA treatment versus the control during senescence. Further analysis showed that most of the identified DEGs were enriched in ROS, respiratory metabolism, and phytohormone pathways, and a total of 50 classes of transcription factors that were possibly involved in modulating these DEGs were obtained. The transcriptional levels of 18 DEGs were verified by Quantitative real-time PCR (qRT-PCR), which confirmed the accuracy of the transcriptomic data. Overall, these findings and data provide a comprehensive view of physiological and molecular events concerning with the CTK-mediated leaf senescence and -maintained quality in economical leafy vegetables.

Synchronization dynamics in response to plaid stimuli in monkey V1.

Gamma synchronization has generally been associated with grouping processes in the visual system. Here, we examine in monkey V1 whether gamma oscillations play a functional role in segmenting surfaces of plaid stimuli. Local field potentials (LFPs) and spiking activity were recorded simultaneously from multiple sites in the opercular and calcarine regions while the monkeys were presented with sequences of single and superimposed components of plaid stimuli. In accord with the previous studies, responses to the single components (gratings) exhibited strong and sustained gamma-band oscillations (30-65 Hz). The superposition of the second component, however, led to profound changes in the temporal structure of the responses, characterized by a drastic reduction of gamma oscillations in the spiking activity and systematic shifts to higher frequencies in the LFP ( approximately 10% increase). Comparisons between cerebral hemispheres and across monkeys revealed robust subject-specific spectral signatures. A possible interpretation of our results may be that single gratings induce strong cooperative interactions among populations of cells that share similar response properties, whereas plaids lead to competition. Overall, our results suggest that the functional architecture of the cortex is a major determinant of the neuronal synchronization dynamics in V1.

Upregulation of TMEM45A Promoted the Progression of Clear Cell Renal Cell Carcinoma in vitro.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive type of primary kidney cancer worldwide. Transmembrane protein 45A (TMEM45A) has been reported to be closely associated with the progression of several cancers. However, the role of TMEM45A in ccRCC remains unclear. Our study intended to explore the potential role of TMEM45A in ccRCC. METHODS: Data on the expression of TMEM45A were obtained from multiple databases, including UCSC, GEPIA2, Oncomine and TIMER. Real-world samples of ccRCC and paired normal renal tissues were used to confirm the information obtained from the databases. In addition, the prognostic value of TMEM45A was evaluated. Loss-of-function assays were performed using TMEM45A-targeting lentivirus to evaluate the biological role of TMEM45A in renal cancer cells. Gene set enrichment analysis (GSEA) was performed to investigate the potential molecular mechanisms. RESULTS: TMEM45A was significantly overexpressed in patients with ccRCC and correlated with poor overall survival and disease-free survival. In addition, the expression of TMEM45A was closely associated with various clinicopathological parameters such as histological grade and TNM stage. Knockdown of TMEM45A inhibited the proliferation and migration and promoted the apoptosis of ccRCC cells in vitro. The results of the GSEA suggested that TMEM45A was potentially involved in the promotion of epithelial-mesenchymal transition (EMT) and inflammatory response in ccRCC. CONCLUSION: TMEM45A was overexpressed and associated with poor survival and acted as a tumour promoter in ccRCC; therefore, might be a potential prognostic marker and therapeutic target.

Prognostic Value of an m5C RNA Methylation Regulator-Related Signature for Clear Cell Renal Cell Carcinoma.

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and is one of the most lethal types of cancer within the urinary system. Aberrant expression of 5-methylcytosine (m5C) RNA methylation regulators has been shown to result in occurrence and progression of tumors. However, the role of these regulators in ccRCC remains unclear. MATERIALS AND METHODS: We extracted RNA sequencing expression data with corresponding clinical information of patients with ccRCC from The Cancer Genome Atlas (TCGA) database. We then compared the expression profiles of m5C RNA methylation regulators between normal and ccRCC tissues, and determined different subtypes through consensus clustering analysis. In addition, we constructed a prognostic signature and evaluated it using a range of bioinformatics approaches. The expression of signature-related genes was subsequently verified in the clinical samples using qRT-PCR. RESULTS: We identified 12 differentially expressed m5C RNA methylation regulators between cancer and normal control samples. Two clusters of patients with ccRCC and diverse clinicopathological characteristics and prognoses were then determined through consensus clustering analysis. Functional annotations revealed that m5C RNA regulators were significantly correlated with the ccRCC progression. Moreover, we constructed a four-gene risk score signature (comprised of NOP2, NSUN4, NSUN6, and TET2) and divided the patients with ccRCC into high- and low-risk groups based on the median risk score. The risk score was associated with clinicopathological features and was an independent prognostic indicator of ccRCC. Our stratified analysis results suggest that the signature has high prognostic value. Based on qRT-PCR results, the NOP2 and NSUN4 mRNA expressions were higher and those of NSUN6 and TET2 were lower in ccRCC tissues than in normal tissues. CONCLUSION: Our results demonstrate that m5C RNA methylation regulators may affect ccRCC progression and could be exploited for diagnostic and prognostic purposes.

Suppression of ANT2 by miR-137 Inhibits Prostate Tumorigenesis.

Prostate cancer (PCa) is a serious disease that affects men's health. To date, no effective and long-lasting treatment option for this condition is available in clinical practice. ANT2 is highly expressed in a variety of hormone-related cancers, but its relationship and regulatory mechanism with PCa are unclear. In this study, we found that ANT2 expression was significantly upregulated in PCa tissues relative to control samples. Genetic knockdown of ANT2 effectively inhibited, while overexpression promoted, proliferation, migration, and invasion of PCa cells. In addition, miR-137 expression was reduced in prostate cancer tissues relative to control tissues. We identified a regulatory site for miR-137 in the 3'-UTR of ANT2 mRNA; luciferase reporter assays indicated that ANT2 is a direct target gene for miR-137. Transfecting cells with miR-137 mimics and/or an ANT2-encoding plasmid revealed that ANT2 promotes proliferation, migration, and invasion of PCa, whereas co-expression of miR-137 mimics inhibited these behaviors. These observations suggest that miR-137 mimics inhibit development of PCa by antagonizing expression of ANT2. Furthermore, tumorigenic assays in nude mice showed that miR-137 inhibitors abolished the inhibitory effect of ANT2 knockdown on PCa tumor growth. Collectively, our findings suggest that ANT2, a target gene of miR-137, is intimately involved in development of PCa, providing new evidence for the mechanism underlying pathogenesis of PCa as well as new options for targeted therapy.

Downregulation of PPA2 expression correlates with poor prognosis of kidney renal clear cell carcinoma.

BACKGROUND: Kidney renal clear cell carcinoma (KIRC) is the most common subtype of kidney cancer. Inorganic pyrophosphatase (PPA2) is an enzyme that catalyzes the hydrolysis of pyrophosphate to inorganic phosphate; few studies have reported its significance in cancers. Therefore, we aimed to explore the prognostic value of PPA2 in KIRC. METHODS: PPA2 expression was detected via immunohistochemistry in a tissue chip containing specimens from 150 patients with KIRC. We evaluated the correlation between PPA2 expression, clinicopathological characteristics, and survival. Data from online databases and another cohort (paraffin-embedded specimens from 10 patients with KIRC) were used for external validation. RESULTS: PPA2 expression was significantly lower in KIRC tissues than in normal renal tissues (p < 0.0001). Low expression of PPA2 was significantly associated with a high histologic grade and poor prognosis. The differential expression of PPA2 was validated at the gene and protein levels. Multivariate Cox regression analysis showed that PPA2 expression was an independent prognostic factor in patients with KIRC. Gene set enrichment analysis suggested that decreased expression of PPA2 might be related to the epithelial-mesenchymal transition in KIRC. CONCLUSIONS: Our study demonstrated that PPA2 is an important energy metabolism-associated biomarker correlated with a favorable prognosis in KIRC.

Construction and validation of a seven-gene signature for predicting overall survival in patients with kidney renal clear cell carcinoma via an integrated bioinformatics analysis.

Kidney renal clear cell carcinoma (KIRC) remains a significant challenge worldwide because of its poor prognosis and high mortality rate, and accurate prognostic gene signatures are urgently required for individual therapy. This study aimed to construct and validate a seven-gene signature for predicting overall survival (OS) in patients with KIRC. The mRNA expression profile and clinical data of patients with KIRC were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC). Prognosis-associated genes were identified, and a prognostic gene signature was constructed. Then, the prognostic efficiency of the gene signature was assessed. The results obtained using data from the TCGA were validated using those from the ICGC and other online databases. Gene set enrichment analyses (GSEA) were performed to explore potential molecular mechanisms. A seven-gene signature (PODXL, SLC16A12, ZIC2, ATP2B3, KRT75, C20orf141, and CHGA) was constructed, and it was found to be effective in classifying KIRC patients into high- and low-risk groups, with significantly different survival based on the TCGA and ICGC validation data set. Cox regression analysis revealed that the seven-gene signature had an independent prognostic value. Then, we established a nomogram, including the seven-gene signature, which had a significant clinical net benefit. Interestingly, the seven-gene signature had a good performance in distinguishing KIRC from normal tissues. GSEA revealed that several oncological signatures and GO terms were enriched. This study developed a novel seven-gene signature and nomogram for predicting the OS of patients with KIRC, which may be helpful for clinicians in establishing individualized treatments.