STX4 as a potential biomarker for predicting prognosis and guiding clinical treatment decisions in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) represents a frequent subtype of kidney cancer, with the prognosis remaining poor for individuals with metastatic disease. Given its resistance to both radiation and chemotherapy, targeted therapies and immunotherapies have emerged as critical for effective ccRCC treatment. Within this context, the SNARE protein STX4, which is associated with malignant cancer cell migration, provides a promising focus. The underlying mechanism, however, requires further illumination. Furthermore, the influence of STX4 on the ccRCC tumor microenvironment remains to be determined. In our research, we utilized multiple databases and immunohistochemical staining to confirm differential STX4 expression and its prognostic implications. We evaluated the potential tumor-promoting function of STX4 in ccRCC cell lines through molecular studies. Additionally, we conducted functional enrichment analysis to delve deeper into the underlying mechanisms and performed immune infiltration and drug sensitivity analyses to assess the potential of STX4 as a prognostic biomarker and therapeutic target. Our study reveals that STX4 contributes to cancer progression by enhancing AKT expression and stimulating the activation of VEGF signaling pathways. Additionally, STX4 further fosters CD8+ T-cell infiltration and diminishes the percentage of CAFs and M2-TAMs. Our findings suggest that patients presenting higher STX4 levels may exhibit enhanced responsiveness to immunotherapy and higher sensitivity to the medications axitinib and everolimus. Finally, we propose STX4 expression assessment as a novel approach to predict patient response to respective immunotherapies and targeted treatments, hence potentially improving patient outcomes.

CPT2-mediated fatty acid oxidation inhibits tumorigenesis and enhances sorafenib sensitivity via the ROS/PPARγ/NF-κB pathway in clear cell renal cell carcinoma.

Kidney cancer is a common kind of tumor with approximately 400,000 new diagnoses each year. Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of all renal cell carcinomas. Lipid metabolism disorder is a hallmark of ccRCC. With a better knowledge of the importance of fatty acid oxidation (FAO) in cancer, carnitine palmitoyltransferase 2 (CPT2) has gained prominence as a major mediator in the cancer metabolic pathway. However, the biological functions and mechanism of CPT2 in the progression of ccRCC are still unclear. Herein, we performed assays in vitro and in vivo to explore CPT2 functions in ccRCC. Moreover, we discovered that CPT2 induced FAO, which inhibited the generation of reactive oxygen species (ROS) by increasing nicotinamide adenine dinucleotide phosphate (NADPH) production. Additionally, we demonstrated that CPT2 suppresses tumor proliferation, invasion, and migration by inhibiting the ROS/ PPARγ /NF-κB pathway. Gene set enrichment analysis (GSEA) and drug sensitivity analysis showed that high expression of CPT2 in ccRCC was associated with higher sorafenib sensitivity, which was also validated in vitro and in vivo. In summary, our results suggest that CPT2 acts as a tumor suppressor in the development of ccRCC through the ROS/PPARγ/NF-κB pathway. Moreover, CPT2 is a potential therapeutic target for increasing sorafenib sensitivity in ccRCC.

Public awareness, specific knowledge, and worry about mpox (monkeypox): A preliminary community-based study in Shenzhen, China.

Background: The mpox (monkeypox) outbreak has been declared to be a public health emergency of international concern by the Director-General of World Health Organization in July 2022. However, evidence regarding the awareness, knowledge, and worry about mpox in the general population remains scant. Methods: A community-based survey targeting community residents was preliminarily conducted in Shenzhen, China in August 2022 by using a convenience sampling method. Information on mpox-related awareness, knowledge, and worry was collected from each participant. Binary logistic regression analyses with the stepwise procedure were applied to explore the factors associated with awareness, knowledge, and worry about mpox. Results: A total of 1028 community residents were included in the analysis (mean age: 34.70 years). Among these participants, 77.9% had ever heard of mpox, and 65.3% were aware of the global outbreak of mpox. However, only about half of them had a high level of knowledge regarding mpox (56.5%) and related symptoms (49.7%). More than one-third of them (37.1%) expressed a high level of worry about mpox. Having high knowledge levels of mpox and related symptoms were positively associated with a high level of worry (OR: 1.79, 95%CI: 1.22~2.63 for a single high knowledge level; OR: 1.98, 95%CI: 1.47~2.66 for both high knowledge levels). Conclusions: This study identified the gaps in public awareness and specific knowledge of mpox in Chinese people, providing scientific evidence for the prevention and control network of mpox at the community level. Targeted health education programs are of urgent need, which should be implemented along with psychological interventions to release public worry if necessary.

Integrated analysis to identify the AC005154.6/hsa-miR-29c-3p/CCNL2 axis as a novel prognostic biomarker associated with immune infiltration in prostate cancer.

BACKGROUND: Prostate cancer (PCa) is currently the major malignancy in men. It is becoming increasingly clear that competitive endogenous RNA (ceRNA) regulation networks are important in a wide variety of cancers. Nevertheless, there is still much to learn about the biological functions of the ceRNA network in prostate cancer. METHODS: The ceRNA network was constructed using the "GDCRNATools" package. Based on survival analysis, we obtained AC005154.6/hsa-miR-29c-3p/CCNL2 for further analysis. The prognostic model based on this ceRNA network was constructed by univariate and multivariate Cox regression methods. Furthermore, functional enrichment analysis, mutation landscape analysis, immune infiltration analysis, drug sensitivity analysis, methylation analysis, pan-cancer analysis, and molecular experiments of CCNL2 were carried out to investigate the role of CCNL2 in tumorigenesis. RESULTS: We identified the AC005154.6/CCNL2 axis as a risk factor that can promote the progression of prostate cancer by bioinformatics analysis and molecular experiments. Immune infiltration analysis suggested that CCNL2 may act as a novel biomarker for treatment decisions. The methylation level of CCNL2 was significantly decreased in tumor samples, possibly contributing to the upregulation of CCNL2 in prostate cancer. Moreover, CCNL2 is differentially expressed in multiple cancers and is tightly correlated with immune infiltration. CONCLUSION: The current study constructed a ceRNA network, AC005154.6/hsa-miR-29c-3p/CCNL2. Potentially, this biomarker can be used for early diagnosis and decision-making about prostate cancer treatment.

Identification of Calcium Channel-Related Gene P2RX2 for Prognosis and Immune Infiltration in Prostate Cancer.

Prostate cancer is one of the most common malignancies in men. Calcium signaling is implicated in the progression of prostate cancer and plays a critical role in immune cell function. However, whether specific calcium channel-related genes play a crucial role in the immune cell infiltration levels of prostate cancer requires further research. In this study, we performed an integrated analysis of transcriptional, clinical, and somatic mutation data from The Cancer Genome Atlas database and identified the hub calcium channel-related gene P2RX2 to be associated with the prognosis and immune infiltration of prostate cancer. P2RX2 expression was positively correlated with immune cell infiltration levels and the expression of immune checkpoint genes, and downregulation of P2RX2 led to poor survival in patients with prostate cancer. Furthermore, we validated the molecular and clinical characteristics of P2RX2 by using multiple databases and conducting in-vitro experiments. Additionally, drug sensitivity analysis revealed that patients with low P2RX2 expression were sensitive to docetaxel and Bicalutamide. In conclusion, we revealed an association between calcium channel-related genes and prostate cancer, and identified P2RX2 as a biomarker for early diagnosis, prognosis prediction, and aiding treatment decisions for patients with prostate cancer.

A predictive signature based on enhancer RNA associates with immune infiltration and aids treatment decision in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a prevalent urinary malignancy. Despite the recent development of better diagnostic tools and therapy, the five-year survival rate for individuals with advanced and metastatic ccRCC remains dismal. Unfortunately, ccRCC is less susceptible to radiation and chemotherapy. Consequently, targeted therapy and immunotherapy play a crucial role in the treatment of ccRCC. Enhancer RNAs (eRNAs) are noncoding RNAs transcribed by enhancers. Extensive research has shown that eRNAs are implicated in a variety of cancer signaling pathways. However, the biological functions of eRNAs have not been systematically investigated in ccRCC. In this study, we conducted a comprehensive investigation of the role of eRNAs in the onset and management of ccRCC. Patient prognosis-influencing eRNAs and target genes were chosen to construct a predictive signature. On the basis of the median riskscore, ccRCC patients were split into high- and low-risk subgroups. The prediction efficiency was assessed in several cohorts, and multi-omics analysis was carried out to investigate the differences and underlying mechanisms between the high- and low-risk groups. In addition, we investigated its potential to facilitate clinical treatment choices. The riskscore might be used to forecast a patient's response to immunotherapy and targeted therapy, giving a revolutionary method for selecting treatment regimens with pinpoint accuracy.

Comprehensive analysis to identify the RP11-478C19.2/ E2F7 axis as a novel biomarker for treatment decisions in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC), accounting for 70-80% of all renal cell carcinomas, is a common malignancy. Survival rates decrease significantly in patients with advanced and metastatic ccRCC. Furthermore, ccRCC is less responsive to radiation and chemotherapy than other cancers. Therefore, targeted therapy and immunotherapy are particularly important for ccRCC management. A growing body of literature recognizes that competitive endogenous RNA (ceRNA) regulatory networks play a crucial role in various cancers. However, the biological functions of the ceRNA network in ccRCC require further investigation. In this study, we built the ceRNA network for ccRCC using the "GDCRNATools" package. After survival analysis, the RP11-478C19.2/hsa-miR-181b-5p, hsa-miR-181a-5p, and hsa-miR-181c-5p/E2F7 axes were obtained for further analysis. Unsupervised clustering was conducted basing on this ceRNA network. The results indicated that the prognosis and immune infiltration levels differed between the two clusters. Furthermore, we conducted correlation analysis, immune infiltration analysis, tumor mutation burden analysis, GSEA analysis, drug sensitivity analysis and pan-cancer analysis of E2F7 to explore its potential role in oncogenesis. Experiments in vitro were performed to confirm the pro-oncogenic impact of E2F7. The results suggest that the RP11-478C19.2/E2F7 axis might be a biomarker for the inclusion of cabozantinib, pazopanib, sunitinib, and immunotherapy in the therapeutic regimen. In summary, we found that the ceRNA-based RP11-478C19.2/E2F7 axis is involved in ccRCC and that it could be a novel biomarker for treatment decisions and a possible therapeutic target to increase the success of targeted therapy and immunotherapy in ccRCC.

Identification of a Gene Signature to Aid Treatment Decisions by Integrated Analysis of Mutated Genes Between Primary and Metastatic Prostate Cancer.

Prostate cancer is one of the most common malignancies in males. Despite the recent development of advanced diagnostic platforms and treatment, patients with metastatic disease still have a poor five-year survival rate. Cancer metastasis is correlated with the characteristics of the tumor microenvironment and is significantly associated with patient prognosis. In this study, we obtained mutated genes with significant differences between primary and metastatic prostate cancer from the COSMIC database. Unsupervised consensus clustering was used based on the 1,051 genes obtained, and two PCa clusters were identified, which exhibited different prognostic outcomes and immune characteristics. Next, we generated a scoring system and evaluated the prognostic value of riskscore and its potential to aid treatment decisions in clinical practice. The riskscore could be applied to predict patients' response to immunotherapy and sensitivity to Docetaxel. In conclusion, this study performed an integrated analysis of mutated genes between primary and metastatic prostate cancer and provides a novel assessment scheme to precisely select treatment strategies.

Identification of RNA-binding protein SNRPA1 for prognosis in prostate cancer.

Prostate cancer is one of the deadliest cancers in men. RNA-binding proteins play a critical role in human cancers; however, whether they have a significant effect on the prognosis of prostate cancer has yet to be elucidated. In the present study, we performed a comprehensive analysis of RNA sequencing and clinical data from the Cancer Genome Atlas dataset and obtained differentially expressed RNA-binding proteins between prostate cancer and benign tissues. We constructed a protein-protein interaction network and Cox regression analyses were conducted to identify prognostic hub RNA-binding proteins. SNRPA1 was associated with the highest risk of poor prognosis and was therefore selected for further analysis. SNRPA1 expression was positively correlated with Gleason score and pathological TNM stage in prostate cancer patients. Furthermore, the expression profile of SNRPA1 was validated using the Oncomine, Human Protein Atlas, and Cancer Cell Line Encyclopedia databases. Meanwhile, the prognostic profile of SNRPA1 was successfully verified in GSE70769. Additionally, the results of molecular experiments revealed the proliferative role of SNRPA1 in prostate cancer cells. In summary, our findings evidenced a relationship between RNA-binding proteins and prostate cancer and indicated the prognostic significance of SNRPA1 in prostate cancer.

A four-gene signature associated with clinical features can better predict prognosis in prostate cancer.

Prostate cancer (PCa) is one of the most deadly urinary tumors in men globally, and the 5-year over survival is poor due to metastasis of tumor. It is significant to explore potential biomarkers for early diagnosis and personalized therapy of PCa. In the present study, we performed an integrated analysis based on multiple microarrays in the Gene Expression Omnibus (GEO) dataset and obtained differentially expressed genes (DEGs) between 510 PCa and 259 benign issues. The weighted correlation network analysis indicated that prognostic profile was the most relevant to DEGs. Then, univariate and multivariate COX regression analyses were conducted and four prognostic genes were obtained to establish a four-gene prognostic model. And the predictive effect and expression profiles of the four genes were well validated in another GEO dataset, The Cancer Genome Atlas and the Human Protein Atlas datasets. Furthermore, combination of four-gene model and clinical features was analyzed systematically to guide the prognosis of patients with PCa to a largest extent. In summary, our findings indicate that four genes had important prognostic significance in PCa and combination of four-gene model and clinical features could achieve a better prediction to guide the prognosis of patients with PCa.

Determinants of Brachial-Ankle Pulse Wave Velocity and Vascular Aging in Healthy Older Subjects.

BACKGROUND Vascular aging is characterized by increasing arterial stiffness as measured by pulse wave velocity. The present study evaluated the factors influencing vascular aging in Chinese healthy older subjects. MATERIAL AND METHODS Disease- and treatment-free aged (≥60 years) participants were recruited from 2014 to 2019. Cardiometabolic risk factors and brachial-ankle pulse wave velocity (baPWV) were assessed. We defined healthy vascular aging (HVA) as the lowest 10% and early vascular aging (EVA) as the highest 10% of the baPWV distribution, after adjustment for age and blood pressure (BP). We fitted linear and logistic regression models to assess the determinants. RESULTS In all, 794 subjects (mean age 66.5±6.8 years, 71.0% male) were recruited; the 10th and 90th percentiles of baPWV were 1278 cm/s and 1955 cm/s, respectively. Age, BP, heart rate, and triglycerides were all positively associated with baPWV, whereas male subjects and body mass index (BMI) were negatively associated with baPWV. The number of participants diagnosed with either HVA or EVA was 80. Logistic regression models showed that sex, BMI, heart rate, and triglycerides were associated with HVA and EVA after adjustment for age, BP, and other confounding factors. CONCLUSIONS Male, high BMI, low heart rate, and low triglycerides are protective factors for vascular aging in the healthy aged population. Management of BMI, heart rate, triglycerides in a reasonable range may help to alleviate the vascular aging process.

Comparison of two malnutrition risk screening tools with nutritional biochemical parameters, BMI and length of stay in Chinese geriatric inpatients: a multicenter, cross-sectional study.

OBJECTIVES: The aims of this study were to assess malnutrition risk in Chinese geriatric inpatients using Nutritional Risk Screening 2002 (NRS2002) and Mini-Nutritional Assessment (MNA), and to identify the most appropriate nutritional screening tool for these patients. DESIGN: Cross-sectional study. SETTING: Eight medical centres in Hubei Province, China. PARTICIPANTS: A total of 425 inpatients aged ≥70 years were consecutively recruited between December 2014 and May 2016. PRIMARY AND SECONDARY OUTCOME MEASURES: Nutritional risk was assessed using NRS2002, MNA, anthropometric measurements and biochemical parameters within 24 hours of admission. Comorbidities and length of hospitalisation were recorded. Nutritional parameters, body mass index (BMI) and length of hospital stay (LOS) were employed to compare MNA and NRS2002. Kappa analysis was used to evaluate the consistency of the two tools. RESULTS: The average age was 81.2±5.9 years (range, 70-98). The prevalence of undernutrition classified by NRS2002 and MNA was 40.9% and 58.6%, respectively. Patients undergoing malnutrition had lower BMI, haemoglobin, albumin and prealbumin (p<0.05), and longer LOS (p<0.05). The NRS2002 showed moderate agreement (κ=0.521, p<0.001) with MNA. Both tools presented significant correlation with age, BMI and laboratory parameters (p<0.001). In addition, a significant association between both tools and LOS was found (p<0.05). In addition, the NRS2002 was not different from MNA in predicting nutritional risk in terms of the area under the receiver operating characteristic curve (p>0.05). CONCLUSIONS: The results show a relatively high prevalence of malnutrition risk in our sample cohort. We found that NRS2002 and MNA were both suitable in screening malnutrition risk among Chinese geriatric inpatients.