Exploring Causal Relationships between Circulating Inflammatory Proteins and Thromboangiitis Obliterans: A Mendelian Randomization Study.

BACKGROUND: Thromboangiitis obliterans (TAO) is a vascular condition characterized by poor prognosis and an unclear etiology. This study employs Mendelian randomization (MR) to investigate the causal impact of circulating inflammatory proteins on TAO. METHODS: In this MR analysis, summary statistics from a genome-wide association study meta-analysis of 91 inflammation-related proteins were integrated with independently sourced TAO data from the FinnGen consortium's R10 release. Methods such as inverse variance weighting, MR-Egger regression, weighted median approaches, MR-PRESSO, and multivariable MR (MVMR) analysis were utilized. RESULTS: The analysis indicated an association between higher levels of C-C motif chemokine 4 and a reduced risk of TAO, with an odds ratio (OR) of 0.44 (95% confidence interval [CI]: 0.29-0.67; p = 1.4 × 10-4; adjusted p = 0.013). Similarly, glial cell line-derived neurotrophic factor exhibited a suggestively protective effect against TAO (OR: 0.43, 95% CI: 0.22-0.81; p = 0.010; adjusted p = 0.218). Conversely, higher levels of C-C motif chemokine 23 were suggestively linked to an increased risk of TAO (OR: 1.88, 95% CI: 1.21-2.93; p = 0.005; adjusted p = 0.218). The sensitivity analysis and MVMR revealed no evidence of heterogeneity or pleiotropy. CONCLUSION: This study identifies C-C motif chemokine 4 and glial cell line-derived neurotrophic factor as potential protective biomarkers for TAO, whereas C-C motif chemokine 23 emerges as a suggestive risk marker. These findings elucidate potential causal relationships and highlight the significance of these proteins in the pathogenesis and prospective therapeutic strategies for TAO.

Lian-Mei-Yin formula alleviates diet-induced hepatic steatosis by suppressing Yap1/FOXM1 pathway-dependent lipid synthesis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, with a global prevalence of 25%. Patients with NAFLD are more likely to suffer from advanced liver disease, cardiovascular disease, or type II diabetes. However, unfortunately, there is still a shortage of FDA-approved therapeutic agents for NAFLD. Lian-Mei-Yin (LMY) is a traditional Chinese medicine formula used for decades to treat liver disorders. It has recently been applied to type II diabetes which is closely related to insulin resistance. Given that NAFLD is another disease involved in insulin resistance, we hypothesize that LMY might be a promising formula for NAFLD therapy. Herein, we verify that the LMY formula effectively reduces hepatic steatosis in diet-induced zebrafish and NAFLD model mice in a time- and dose-dependent manner. Mechanistically, LMY suppresses Yap1-mediated Foxm1 activation, which is crucial for the occurrence and development of NAFLD. Consequently, lipogenesis is ameliorated by LMY administration. In summary, the LMY formula alleviates diet-induced NAFLD in zebrafish and mice by inhibiting Yap1/Foxm1 signaling-mediated NAFLD pathology.

Endovascular recanalization for pediatric hypertension secondary to total renal artery occlusion.

PURPOSE: To assess the feasibility and efficacy of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) secondary to total renal artery occlusion (RAO). METHODS: From 2011 to 2021, 13 pediatric patients with RVH confirmed with 14 occluded renal artery lesions were reviewed. The mean age was11.2 years (range 4 to 16). Nine lesions involved main artery occlusion, while five lesions featured branch occlusion. Blood Pressure Ratio (BPR) was defined as the ratio of the actual BP value to the 95th percentile value adjusted for age, gender, and height. RESULTS: PTRA was performed on nine patients (9/13, 69%). Technical success was achieved in five patients (5/9, 56%), with stent placement in two children (2/9, 22%). During the 12-month follow-up, restenosis was identified in two stent-receiving patients at the 12-month follow-up visit (2/9, 22%). Mean systolic BPR decreased from 1.20 ± 0.07 to 0.96 ± 0.06 (p = 0.003), mean diastolic BPR decreased from 1.19 ± 0.07 to 0.95±0.08 (p = 0.005) and the number of required medications decreased from 3.8 ± 0.8 to 2.4 ± 0.9 (p = 0.052) following PTRA. Subsequent to PTRA, the mean GFR of the occluded kidney improved from 19.5 ± 12.3 mL/ min to 36.3 ± 10.8 mL/ min (p = 0.007) and the mean longitudinal dimension of the affected kidneys significantly increased from 8.2 ± 1.5 cm to 9.2 ± 1.7 cm (p = 0.006). CONCLUSIONS: Endovascular treatment is feasible for pediatric RAO, results in acceptable BP control and preserves renal function.

Magnetic Resonance Imaging in Atherosclerotic Renal Artery Stenosis: The Update and Future Directions from Interventional Perspective.

Background: Atherosclerotic renal artery stenosis (ARAS) is a condition where the renal arteries become narrowed due to atherosclerosis, leading to reduced blood flow to the kidneys and various renal complications. The effectiveness of interventional treatments, such as renal artery angioplasty and stenting, remains debated, making patient selection for these procedures challenging. Summary: This review focuses on the diagnosis and management of ARAS, with a particular emphasis on the potential role of functional magnetic resonance imaging (MRI) in evaluating renal function and mechanisms. By summarizing current diagnostic approaches and outcomes of interventional treatments, the review highlights the importance of informed clinical decision-making in ARAS management. Functional MRI emerges as a promising noninvasive tool to assess renal function, aiding in patient stratification and treatment planning. Key Messages: The efficacy of interventional treatments for ARAS requires further investigation and careful patient selection. Functional MRI holds promise as a noninvasive means to assess renal function and mechanisms, potentially guiding more effective clinical decisions in ARAS management. Advancing research in diagnostic methods, particularly functional MRI, can enhance our understanding and improve the treatment outcomes for ARAS patients.

[Analysis of O3 Pollution Affected by a Succession of Three Landfall Typhoons in 2020 in Eastern China].

Based on air quality monitoring, surface meteorological data, wind profile radar observation, and the HYSPLIT model, the characteristics and causes of O3 pollution in eastern China during the period of the typhoons BAVI, MAYSAK, and HAISHEN from August 26 to September 8, 2020 were analyzed. The results showed that during the succession of the three landfall typhoons, the O3 pollution sites in Beijing Tianjin Hebei and its surrounding areas (BTHS) and the Yangtze River Delta (YRD) exceeded 50%. During the HAISHEN period, O3 pollution days in the two regions reached 2.22 d and 2.97 d, respectively, with significant persistence characteristics. The location of the typhoon had an obvious influence on O3 concentration. When the typhoons were located within the 24h warning line, the O3 concentrations in BTHS and YRD were relatively low. When the typhoons were located between the 24 h and 48 h warning lines, the O3 concentration in BTHS was the highest. When the typhoons moved north of 34°N, the YRD was most prone to regional O3 pollution. O3 pollution in Shanghai mainly occurred under the control of the northward air flow to the west side of the typhoons, and the regional transport from the upstream area had a significant impact on the increase in O3 and its precursor concentrations. The downdraft below 1 000 m maintained O3 at a high concentration at night. In Jinan, O3 pollution mainly occurred under the control of the subtropical high and typhoon periphery. The downdraft prevailed in the middle and lower levels during the O3 pollution. From August 28 to 30, under the control of the subtropical high, the pollutants were mainly accumulated locally, and some of them were transmitted within the province, showing a "double high" phenomenon of O3 and PM2.5. From September 5 to 8, under the influence of HAISHEN peripheral circulation, the regional transport was obvious, and the O3 concentration increased earlier than that of PM2.5.

[Corrigendum] Long non­coding RNA CASC11 interacts with YBX1 to promote prostate cancer progression by suppressing the p53 pathway.

Subsequently to the publication of the above article, an interested reader drew to the authors' attention that, concerning the Transwell assay experiments shown in Fig. 3G and I on p. 8, the data panel showing the result of the 'LNCaP / sh­CASCS11­1' experiment in Fig. 3G appeared to be overlapping with the 'LNCaP / Vector' experiment in Fig. 3I, even though the data were intended to have shown the results from differently performed experiments. After having re­examined their original data, the authors have realized that Fig. 3G and I were inadvertently assembled incorrectly. The revised version of Fig. 3, showing the correct data for the 'LNCaP / Vector' experiment in Fig. 3I, is shown on on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors thank the interested reader for drawing this matter to their attention, and apologize to the readership for any inconvenience caused. [International Journal of Oncology 61: 110, 2022; DOI: 10.3892/ijo.2022.5400].

Outcomes of percutaneous transluminal renal angioplasty for pediatric renovascular hypertension: a 12-year retrospective single-center experience.

Background: Renovascular disease underlies 5-10% of all childhood hypertension. We evaluated the long-term outcomes of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH). Methods: Data from 37 children with RVH who underwent PTRA of 45 lesions at our center from January 2010 to January 2022 were retrospectively evaluated. Postoperative blood pressure (BP), glomerular filtration rate (GFR), affected kidney size, restenosis, and complications were analyzed. Results: Mean age, weight, and height of patients at first PTRA was 11.51±4.57 (range, 3-17) years, 45.37±22.29 (range, 13.40-106.00) kg, and 1.46±0.26 (range, 0.92-1.85) m, respectively. Technical success was achieved in 33 of 37 (89.2%) patients and 40 of 45 (88.9%) lesions, without surgery-related complications. At a median of 7.5 (range, 3-14) months, restenosis occurred in 6 (16.7%) patients and 7 (16.3%) lesions (all ostial and 6 with a length >15 mm), yielding a clinical beneficial rate from first PTRA of 83.3%. At 18- and 20-month follow-up the mean kidney length (29 kidneys) increased from 8.89±1.55 to 9.79±1.51 cm (P<0.001) and mean GFR (34 kidneys) from 32.28±19.22 to 41.24±13.24 mL/min (P<0.001). Conclusions: In this retrospective analysis, PTRA for the treatment of pediatric RVH can achieve satisfactory results. Angioplasty was associated with improved BP control and long-term preservation of renal function, as reflected by an increase in affected kidney size and a higher GFR.

CH02 peptide promotes ex vivo expansion of umbilical cord blood-derived CD34 + hematopoietic stem/progenitor cells.

Umbilical cord blood (UCB) is an advantageous source for hematopoietic stem/progenitor cell (HSPC) transplantation, yet the current strategies for large-scale and cost-effective UCB-HSPC preparation are still unavailable. To overcome these obstacles, we systematically evaluate the feasibility of our newly identified CH02 peptide for ex vivo expansion of CD34 + UCB-HSPCs. We herein report that the CH02 peptide is specifically enriched in HSPC proliferation via activating the FLT3 signaling. Notably, the CH02-based cocktails are adequate for boosting 12-fold ex vivo expansion of UCB-HSPCs. Meanwhile, CH02-preconditioned UCB-HSPCs manifest preferable efficacy upon wound healing in diabetic mice via bidirectional orchestration of proinflammatory and anti-inflammatory factors. Together, our data indicate the advantages of the CH02-based strategy for ex vivo expansion of CD34 + UCB-HSPCs, which will provide new strategies for further development of large-scale HSPC preparation for clinical purposes.

FGFR4 and EZH2 inhibitors synergistically induce hepatocellular carcinoma apoptosis via repressing YAP signaling.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide, but current treatment options remain limited and cause serious life-threatening side effects. Aberrant FGFR4 signaling has been validated as an oncogenic driver of HCC, and EZH2, the catalytic subunit of the PRC2 complex, is a potential factor that contributes to acquired drug resistance in many tumors, including HCC. However, the functional relationship between these two carcinogenic factors, especially their significance for HCC treatment, remains unclear. In this study, we systematically evaluated the feasibility of a combination therapy targeting FGFR4 and EZH2 for HCC. METHODS: RNA sequencing data of patients with Liver hepatocellular carcinoma (LIHC) from The Cancer Genome Atlas (TCGA) were analyzed to determine FGFR4 and EZH2 expression and their interaction with prognosis. Moreover, the HCC cell lines, zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors were treated with FGFR4 inhibitor (Roblitinib) and/or EZH2 inhibitor (CPI-169) and then subjected to cell proliferation, viability, apoptosis, and tumor growth analyses to evaluate the feasibility of combination therapy for HCC both in vitro and in vivo. Furthermore, RNA-Seq was performed in combination with ChIP-Seq data analysis to investigate the critical mechanism underlying the combination treatment with Roblitinib and CPI-169. RESULTS: EZH2 accumulated through the non-canonical NF-kB signaling in response to FGFR4 inhibitor treatment, and the elevated EZH2 levels led to the antagonism of HCC against Roblitinib (FGFR4 inhibitor). Notably, knockdown of EZH2 sensitized HCC cells to Roblitinib, while the combination treatment of Roblitinib and CPI-169 (EZH2 inhibitor) synergistically induced the HCC cell apoptosis in vitro and suppressed the zebrafish/mouse HCC xenografts and zebrafish HCC primary tumors development in vivo. Moreover, Roblitinib and CPI-169 synergistically inhibited HCC development via repressing YAP signaling. CONCLUSIONS: Collectively, our study highlighted the potential of the therapeutic combination of FGFR4 and EZH2 inhibitors, which would provide new references for the further development of clinical treatment strategies for HCC.

Early cerebral hemodynamic changes following unilateral carotid artery stenting in patients with different degrees of carotid stenosis.

Background: Few studies have focused on cerebral hemodynamics in the early stage following carotid artery stenting (CAS). This retrospective cohort study aimed to investigate cerebral hemodynamic changes within 6 hours of unilateral CAS in patients with different degrees of carotid stenosis. Methods: A total of 104 patients who underwent CAS accompanied by transcranial color-code Doppler or transcranial Doppler were enrolled in the study. The participants were divided into the following 3 groups based on the degree of carotid stenosis: severe stenosis group, extreme stenosis group, and near occlusion group. Bilateral middle cerebral artery (MCA) peak systolic velocity (PSV) and pulsatility index (PI) were measured using transcranial color-code Doppler before and 1 and 3 hours following CAS. Blood pressure, MCA-PSV, and PI were compared among the 3 groups. Results: At 1 hour following CAS, ipsilateral MCA-PSV increased compared to the baseline in the severe stenosis group [84±21 vs. 93±27 cm/s; 8.1%; interquartile range (IQR), 1.4-20.1%; P<0.001]. A similar hemodynamic change, but of a larger magnitude, was observed in the extreme stenosis group (83±24 vs. 100±29 cm/s; 20.8%; IQR, 5.3-33.1%; P<0.001) and near occlusion group (73±24 vs. 109±29 cm/s, 45.8%; IQR, 24.3-73.1%; P<0.001). At 3 hours after CAS, the hemodynamic changes were the same as those at 1 hour. PI increased in all 3 groups following CAS. A subgroup analysis was performed according to symptoms, sex, smoking status, history of hypertension, and presence of hyperlipidemia or diabetes, and the increase in ipsilateral MCA-PSV was not significant. In terms of adverse events, only 4 patients in the near occlusion group experienced transient post-CAS hyperperfusion. Conclusions: The ipsilateral MCA-PSV and PI in patients following unilateral CAS increased significantly in the initial hours. The increase in ipsilateral MCA-PSV was considerably higher in patients with a severe degree of stenosis. Near occlusion of the carotid artery was an independent risk factor for hyperperfusion after unilateral CAS.

Role of the Global Limb Anatomic Staging System in predicting outcomes of chronic limb-threatening ischemia in patients treated by drug-coated balloons.

Background: The Global Limb Anatomic Staging System (GLASS) was proposed to assess the procedural complexity and technical failure rate and stratify the anatomic pattern of chronic limb-threatening ischemia (CLTI). However, more evidence is needed to validate the GLASS in staging outcomes after endovascular therapy in patients with CLTI treated with drug-coated balloons (DCBs). This study aims to evaluate the role of the GLASS in predicting outcomes of CLTI patients treated with DCBs. Methods: This multicenter, retrospective cohort study enrolled patients with CLTI treated with DCBs from July 2016 to June 2019. GLASS stages were assigned for every limb. The limb-based patency (LBP) rate, clinically driven target lesion revascularization (CD-TLR) rate, clinical improvement, and safety endpoints were analyzed and compared across the GLASS stages over 12 months of follow-up. Risk factors for the loss of LBP were identified using Cox regression analysis. Results: A total of 90 limbs were enrolled, with 55 (61.1%) having isolated femoropopliteal lesions and 35 (38.9%) having femoropopliteal and infrapopliteal lesions. Of the limbs, 17 (18.9%), 12 (13.3%), and 61 (67.8%) were assigned to GLASS stages I, II, and III, respectively. The Kaplan-Meier estimate of the 12-month LBP was 65.4%, and no difference was found among the different stages (stage I 81.1%; stage II 85.2%; stage III 54.4%; P=0.080). The LBP was lower in stage III than in stages I and II combined (stage I and II 83.5%; stage III 54.4%; P=0.027). Similar results were found for the freedom from CD-TLR rates among the different stages. The ankle-brachial index values improved from 0.42±0.29 to 0.78±0.35 at follow-up (P<0.001). The rates of mortality, any amputation, and major amputation were similar among the groups. GLASS stage III and coronary heart disease were identified as independent risk factors for the loss of LBP at 12 months. Conclusions: The 1-year LBP and freedom from CD-TLR rates were lower in GLASS stage III than in stages I and II. The GLASS classification could predict the outcomes of CLTI patients with femoropopliteal lesions treated with DCB.

Turning gray selenium and sublimed sulfur into a nanocomposite to accelerate tissue regeneration by isothermal recrystallization.

BACKGROUND: Globally, millions of patients suffer from regenerative deficiencies, such as refractory wound healing, which is characterized by excessive inflammation and abnormal angiogenesis. Growth factors and stem cells are currently employed to accelerate tissue repair and regeneration; however, they are complex and costly. Thus, the exploration of new regeneration accelerators is of considerable medical interest. This study developed a plain nanoparticle that accelerates tissue regeneration with the involvement of angiogenesis and inflammatory regulation. METHODS: Grey selenium and sublimed sulphur were thermalized in PEG-200 and isothermally recrystallised to composite nanoparticles (Nano-Se@S). The tissue regeneration accelerating activities of Nano-Se@S were evaluated in mice, zebrafish, chick embryos, and human cells. Transcriptomic analysis was performed to investigate the potential mechanisms involved during tissue regeneration. RESULTS: Through the cooperation of sulphur, which is inert to tissue regeneration, Nano-Se@S demonstrated improved tissue regeneration acceleration activity compared to Nano-Se. Transcriptome analysis revealed that Nano-Se@S improved biosynthesis and ROS scavenging but suppressed inflammation. The ROS scavenging and angiogenesis-promoting activities of Nano-Se@S were further confirmed in transgenic zebrafish and chick embryos. Interestingly, we found that Nano-Se@S recruits leukocytes to the wound surface at the early stage of regeneration, which contributes to sterilization during regeneration. CONCLUSION: Our study highlights Nano-Se@S as a tissue regeneration accelerator, and Nano-Se@S may provide new inspiration for therapeutics for regenerative-deficient diseases.

Hyaluronic acid-FGF2-derived peptide bioconjugates for suppression of FGFR2 and AR simultaneously as an acne antagonist.

Acne is a chronic skin condition that has serious consequences for mental and social well-being because it frequently occurs on the face. Several acne treatment approaches have commonly been used but have been hampered by side effects or weak activity. Thus, the investigation of the safety and efficacy of anti-acne compounds is of considerable medical importance. Herein, an endogenous peptide (P5) derived from fibroblast growth factors 2 (FGF2) was conjugated to the polysaccharide hyaluronic acid (HA) to generate the bioconjugate nanoparticle HA-P5, which suppresses fibroblast growth factor receptors (FGFRs) to significantly rehabilitate acne lesions and reduce sebum accumulation in vivo and in vitro. Moreover, our results show that HA-P5 inhibits both fibroblast growth factor receptor 2 (FGFR2) and androgen receptor (AR) signalling in SZ95 cells, reverses the acne-prone transcriptome, and decreases sebum secretion. Furthermore, the cosuppression mechanism revealed that HA-P5 blocks FGFR2 activation, as well as the YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) downstream molecules, including an N6-methyladenosine (m6A) reader that facilitates AR translation. More importantly, a significant difference between HA-P5 and the commercial FGFR inhibitor AZD4547 is that HA-P5 does not trigger the overexpression of aldo-keto reductase family 1 member C3 (AKR1C3), which blocks acne treatment by catalyzing the synthesis of testosterone. Overall, we demonstrate that a polysaccharide-conjugated and naturally derived oligopeptide HA-P5 can alleviate acne and act as an optimal FGFR2 inhibitor and reveal that YTHDF3 plays a crucial role in signalling between FGFR2 and AR.

Triclocarban triggers osteoarthritis via DNMT1-mediated epigenetic modification and suppression of COL2A in cartilage tissues.

Triclocarban (TCC) is a widely used environmental endocrine-disrupting chemical (EDC). Articular injury of EDCs has been reported; however, whether and how TCCs damage the joint have not yet been determined. Herein, we revealed that exposure to TCC caused osteoarthritis (OA) within the zebrafish anal fin. Mechanistically, TCC stimulates the expression of DNMT1 and initiates DNA hypermethylation of the type II collagen coding gene, which further suppresses the expression of type II collagen and other extracellular matrices. This further results in decreased cartilage tissue and narrowing of the intraarticular space, which is typical of the pathogenesis of OA. The regulation of OA occurrence by TCC is conserved between zebrafish cartilage tissue and human chondrocytes. Our findings clarified the hazard and potential mechanisms of TCC towards articular health and highlighted DNMT1 as a potential therapeutic target for OA caused by TCC.

Case Report: Endovascular Treatment of Chronic Atherosclerotic Renal Artery Total Occlusions with Failed Medical Therapy.

Background: Current guidelines generally no longer support revascularization for chronic renal artery occlusive diseases because results from randomized controlled trials favor medical therapy over angioplasty. However, increasing reports indicate that patients with renal artery occlusion (RAO) can benefit from revascularization under certain circumstances. Case summary: Here, we present a patient with renal artery stenosis (RAS) who does not have refractory hypertension or fit any clinical trial inclusion criteria by far. Medical therapy failed to prevent the progression of RAS in this patient, leading to total occlusion of his right renal artery. This patient had progressive renal insufficiency but recovered renal function after endovascular treatment. Conclusion: This case demonstrates that angioplasty can be beneficial in selected RAO patients, especially those with residual renal function and collateral perfusion.

Contrast-enhanced magnetic resonance angiography for monitoring an embolized renal artery aneurysm: A case report and literature review.

This case report describes a 69-year-old male patient with a renal artery aneurysm that was followed up with contrast-enhanced magnetic resonance angiography at 8 months after coil embolization treatment. Due to the disappearance of residual lumen with few metal artifacts, the therapeutic effect was satisfactory. At present, the indications for the treatment of renal artery aneurysms are still controversial and there are very few reports of postembolization images of renal artery aneurysms, with no criteria for reintervention and few reports for monitoring the embolized aneurysms. Further reports and research are still needed for the treatment of this rare disease.

Identification of cuproptosis -related subtypes, the development of a prognosis model, and characterization of tumor microenvironment infiltration in prostate cancer.

Cuproptosis, Copper Induced Cell Death, is a newly defined type of programmed cell death, involving in the regulation of tricarboxylic acid (TCA) cycle. Dysfunction of cuproptosis induces cytotoxicity and influences the proliferation of multiple tumors. However, the direct prognostic effect of cuproptosis related genes and corresponding regulating mechanisms amid prostate cancer remains unknown. A multi-omics analysis strategy was adopted to explore the role of ten cuproptosis related genes in The Cancer Genome Atlas- Prostate Adenocarcinoma (TCGA-PRAD). Firstly, mRNA expression, Copy Number Variance (CNV), mutation, DNA methylation and prognostic power of the ten genes were illustrated. Based on transcriptomic data, we developed a novel prognostic model named the Cuproptosis-related gene score (CRGScore), Their biological functions were then detected by enrichment analysis and unsupervised cluster analysis. Following that, their correlation with Tumor Immune Microenvironment (TIME), immunotherapy, Biochemical Recurrence (BCR) and chemotherapeutic resistance were elaborated by relevant bioinformatics algorithms. Ten cuproptosis related genes exhibited extensive alteration of CNV and DNA methylation and showed significant influence on the prognosis of prostate cancer patients. These genes mainly enriched in E2F and G2M targets and mitosis pathways, Samples with high CRGScore showed enhancement resulting in the increased infiltration of T cell, B cell, NK cells. They also demonstrated close correlations with the BCR status, expression of eight immune checkpoints and chemotherapeutic resistances in prostate cancer. Our comprehensive analysis of CRGScore revealed an extensive regulatory mechanism by which they affect the tumor-immune-stromal microenvironment, clinicopathological features, and prognosis. We also determined the therapeutic liability of CRGScore in targeted therapy and immunotherapy. These findings highlight the crucial clinical implications of CRGScore and provide new ideas for guiding personalized immunotherapy strategies for patients with Pca.

Computer classification and construction of a novel prognostic signature based on moonlighting genes in prostate cancer.

Advanced prostate cancer (PRAD) patients have poor prognosis and rising morbidity despite the ongoing iteration of molecular therapeutic agents. As newly discovered proteins with several functions, Moonlighting proteins have showed an important role in tumor progression but has not been extensively investigated in PRAD. Our study aimed to identify moonlighting-related prognostic biomarkers and prospective PRAD therapy targets. 103 moonlighting genes were gathered from previous literatures. A PRAD classification and multivariate Cox prognostic signature were constructed using dataset from The Cancer Genome Atlas (TCGA). Subsequently, we tested our signature's potential to predict biochemical failure-free survival (BFFS) using GSE21032, a prostate cancer dataset from Gene Expression Omnibus (GEO). The performance of this signature was demonstrated by Kaplan-Meier (KM), receiver operator characteristic (ROC), areas under ROC curve (AUC), and calibration curves. Additionally, immune infiltration investigation was conducted to determine the impact of these genes on immune system. This signature's influence on drug susceptibility was examined using CellMiner's drug database. Both training and validation cohorts demonstrated well predictive capacity of this 9-gene signature for PRAD. The 3-year AUCs for TCGA-PRAD and GSE21032 were 0.802 and 0.60 respectively. It can effectively classify patients into various biochemical recurrence risk groups. These genes were also assessed to be connected with tumor mutation burden (TMB), immune infiltration and therapy. This work created and validated a moonlighting gene signature, revealing fresh perspectives on moonlighting proteins in predicting prognosis and improving treatment of PRAD.