Corrigendum: Machine learning to construct sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with uveal melanoma.

[This corrects the article DOI: 10.3389/fendo.2022.1056310.].

Deciphering a Prognostic Signature Based on Soluble Mediators Defines the Immune Landscape and Predicts Prognosis in HNSCC.

BACKGROUND: The study on Head and Neck Squamous Cell Carcinoma (HNSCC), a prevalent and aggressive form of head and neck cancer, focuses on the often-overlooked role of soluble mediators. The objective is to leverage a transcriptome-based risk analysis utilizing soluble mediator-related genes (SMRGs) to provide novel insights into prognosis and immunotherapy efficacy in HNSCC patients. METHODS: We analyzed the expression and prognostic significance of 10,859 SMRGs using 502 HNSCC and 44 normal samples from the TCGA-HNSC cohort in The Cancer Genome Atlas (TCGA). The samples were divided into training and test sets in a 7:3 ratio, with an additional external validation using 40 tumor samples from the International Cancer Genome Consortium (ICGC). Key differentially expressed genes (DEGs) with prognostic significance were identified through univariate and Lasso-Cox regression analyses. A prognostic model based on 20 SMRGs was developed using Lasso and multivariate Cox regression. We assessed the clinical outcomes and immune status in high-risk (HR) and low-risk (LR) HNSCC patients utilizing the BEST databases and single-sample Gene Set Enrichment Analysis (ssGSEA). RESULTS: The 20 SMRGs were crucial in predicting the prognosis of HNSCC, with the SMRG signature emerging as an independent prognostic indicator. Patients classified in the HR group exhibited poorer outcomes compared to those in the LR group. A nomogram, integrating clinical characteristics and risk scores, demonstrated substantial prognostic value. Immunotherapy appeared to be more effective in the LR group, possibly attributed to enhanced immune infiltration and expression of immune checkpoints. CONCLUSIONS: The model based on soluble mediator-associated genes offers a fresh perspective for assessing the pre-immune efficacy and showcases robust predictive capabilities. This innovative approach holds significant promise in advancing the field of precision immuno-oncology research, providing valuable insights for personalized treatment strategies in HNSCC.

Ralstonia solanacearum differentially modulates soil physicochemical properties and rhizospheric bacteriome of resistant and susceptible tobacco cultivars.

Ralstonia solanacearum is a devastating soilborne pathogen which poses significant yield and economic losses to tobacco production globally. The impact of R. solanacearum on rhizosphere bacteriome and soil physicochemical characteristics in resistant and susceptible tobacco cultivars is poorly understood. This study aims to determine the effect of R. solanacearum on soil physicochemical parameters and rhizosphere bacteriome of resistant (K326) and susceptible (Hongda) tobacco cultivars at various growth stages. Results demonstrated that the contents of available potassium and phosphorus, as well as soil pH were significantly increased in K326 soils (CK and T2) compared with Hongda (T1) after 21, 42, and 63 days post-inoculation (dpi) of R. solanacearum except for available nitrogen which showed an opposite trend. The qPCR results showed a significant decrease in R. solanacearum population in rhizosphere of K326 (T2) compared to the Hongda (T1) at 21 and 63 dpi than that after 42 dpi. The rhizosphere bacteriome analysis through 16S rRNA amplicon sequencing revealed that rhizosphere bacterial community composition was significantly different between two tobacco cultivars (Hongda and K326) and this effect was more prominent after 63 dpi (93 days after post-transplantation), suggesting that each cultivar recruits a unique set of bacterial communities. There was no obvious difference observed in the rhizosphere bacteriome of CK (K326) and T2 (K326), which might be attributed to the same genetic makeup and inherent resistance of K326 to bacterial wilt infection. Analysis of co-occurrence networks revealed that the microbial network in T1 (Hongda) was more complex than those in T2 (K326) and CK (K326), while the networks in CK and T2 were almost identical. The present research highlights the time-course relationship between environmental factors and rhizosphere bacteriome of tobacco cultivars showing different levels of resistance against R. solanacearum. Conclusively, studying the plant-soil-microbe interaction system in susceptible and resistant tobacco cultivars may enable us to develop effective integrated disease control plans for the healthy production of tobacco crops.

Sequential pre-disinfection with chlorhexidine and alcohol reduces periprosthetic joint infection after primary knee arthroplasty: A case-control study.

A retrospective case-control study was conducted to assess whether patients who underwent sequential preoperative disinfection before primary total knee or unicompartmental arthroplasty had a lower rate of postoperative infection than those who did not. In our study, 1025 patients who underwent total knee or unicompartmental arthroplasty at 2 medical centers between September 1, 2020, and August 31, 2021, were enrolled. Statistical analysis was performed for 976 cases, including 966 and 10 uninfected and infected cases, respectively. All patients were followed up for 1-year. Data analysis was performed by binary logistic regression and adjusted for 2 confounding factors: general anesthesia and rheumatoid arthritis. IBM SPSS for Windows (version 25.0; IBM Co., Armonk, NY) software was used to perform all statistical analyses. During the study period, of the 976 patients, 10 cases of infections were detected. Sequential pre-disinfection (adjusted odds ratio 0.14, 95% confidence interval: 0.03-0.54, P = .005) could reduce the incidence of infection. Based on the results of this study, bathing the whole lower limb with 2% chlorhexidine on the night before surgery followed by 70% alcohol application 1 hour before surgery is effective for preventing periprosthetic joint infection during primary total knee or unicompartmental arthroplasty.

Prevention and Control of Coal and Gas Outburst by Directional Hydraulic Fracturing through Seams and Its Application.

The regionalized pressure relief, permeability enhancement, and outburst prevention of "three high and one low" coal seams with high gas, high ground stress, high outburst risk, and low permeability have become important problems to be solved urgently in realizing the sustainable development of coal mines. In this study, a combination of theoretical research, RFPA2D-Flow numerical simulation, and field test was used to study the initiation mechanism and propagation law of directional hydraulic fracturing fractures through the seam. The results show that fracture initiation depends on the axial and radial horizontal stress of the fracture hole, the physical and mechanical properties of coal and rock, and the inside of the weakest layer. Single-hole hydraulic fracturing can achieve a pressure relief radius of 7-8 m, but there is a stress concentration zone outside, which is not conducive to regional pressure relief and permeability enhancement. Directional hydraulic fracturing with multiple holes produces an approximate cylindrical compression and crushing ring and a penetrating fracture surface along the center line of the pressure crack hole and the directional hole, which better eliminates the phenomenon of stress concentration in nondirectional hydraulic fracturing. The technology was applied to the 2238 auxiliary roadway of Chengzhuang Mine of Jinmei Group, and the field implementation results showed that field implementation results showed that directional hydraulic fracturing through the seam reduced the gas content in the coal seam to a great extent, and the coal seam gas content was reduced by about 42.3%, indicating that the technology can effectively reduce the risk of coal and gas outbursts.

Deciphering the role of HPV-mediated metabolic regulation in shaping the tumor microenvironment and its implications for immunotherapy in HNSCC.

Head and neck squamous cell carcinoma (HNSCC), as a complex and variable malignancy, poses a significant threat to human health. Since the intricate association between HPV and HNSCC emerged, its role within the TME has garnered extensive attention. HPV+HNSCC exhibits distinct immunological characteristics within the TME, intricately intertwined with mechanisms of immune evasion. HPV employs multifaceted pathways to intervene in metabolic regulation within the TME, exerting influence over immune cell functionality and neoplastic cell genesis. Furthermore, the heightened immune reactivity exhibited by HPV+HNSCC within the TME augments responses to immune interventions such as immune checkpoint inhibitors. Therefore, amidst the current limitations of therapeutic approaches, immunotherapy stands as a promising strategy to overcome the conventional confines of treating HNSCC. This article comprehensively outlines the impact of HPV on the inception and progression of HNSCC while discussing the amalgamation of metabolic regulation within the TME and immunotherapeutic strategies. By intervening in the reciprocal interactions between HPV and HNSCC within the TME, the potential to modulate the efficacy of immune-based treatments becomes evident. Concurrently, a synthesis of pertinent biomarker development is summarized. Such endeavors hold paramount significance for personalized therapeutic approaches and the more effective management of HNSCC patients.

Decoding tumor heterogeneity in uveal melanoma: basement membrane genes as novel biomarkers and therapeutic targets revealed by multi-omics approaches for cancer immunotherapy.

Background: Uveal melanoma (UVM) is a primary intraocular malignancy that poses a significant threat to patients' visual function and life. The basement membrane (BM) is critical for establishing and maintaining cell polarity, adult function, embryonic and organ morphogenesis, and many other biological processes. Some basement membrane protein genes have been proven to be prognostic biomarkers for various cancers. This research aimed to develop a novel risk assessment system based on BMRGs that would serve as a theoretical foundation for tailored and accurate treatment. Methods: We used gene expression profiles and clinical data from the TCGA-UVM cohort of 80 UVM patients as a training set. 56 UVM patients from the combined cohort of GSE84976 and GSE22138 were employed as an external validation dataset. Prognostic characteristics of basement membrane protein-related genes (BMRGs) were characterized by Lasso, stepwise multifactorial Cox. Multivariate analysis revealed BMRGs to be independent predictors of UVM. The TISCH database probes the crosstalk of BMEGs in the tumor microenvironment at the single-cell level. Finally, we investigated the function of ITGA5 in UVM using multiple experimental techniques, including CCK8, transwell, wound healing assay, and colony formation assay. Results: There are three genes in the prognostic risk model (ADAMTS10, ADAMTS14, and ITGA5). After validation, we determined that the model is quite reliable and accurately forecasts the prognosis of UVM patients. Immunotherapy is more likely to be beneficial for UVM patients in the high-risk group, whereas the survival advantage may be greater for UVM patients in the low-risk group. Knockdown of ITGA5 expression was shown to inhibit the proliferation, migration, and invasive ability of UVM cells in vitro experiments. Conclusion: The 3-BMRGs feature model we constructed has excellent predictive performance which plays a key role in the prognosis, informing the individualized treatment of UVM patients. It also provides a new perspective for assessing pre-immune efficacy.

Preparation, characterization and biocompatibility of calcium peroxide-loaded polycaprolactone microparticles. / èšå·±å† é ¯åŒ è½½è¿‡æ°§åŒ–é’™å¾®ç²’çš„åˆ¶å¤‡ã€è¡¨å¾åŠå ¶ç”Ÿç‰©ç›¸å®¹æ€§ç ”ç©¶.

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O2 and H2O2 after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O2 and H2O2 released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS: CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.

Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer.

The ubiquitin-proteasome system (UPS) controls protein turnover, and its dysfunction contributes to human diseases including cancer. Deubiquitinating enzymes (DUBs) remove ubiquitin from proteins to maintain their stability. Inhibition of DUBs could induce the degradation of selected oncoproteins and has therefore become a potential therapeutic strategy for cancer. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Here, we report a small-molecule inhibitor of OTUD3 (named OTUDin3) by computer-aided virtual screening and biological experimental verification. OTUDin3 exhibited pronounced antiproliferative and proapoptotic effects by inhibiting deubiquitinating activity of OTUD3 in non-small-cell lung cancer (NSCLC) cell lines. Moreover, OTUDin3 efficaciously inhibited growth of lung cancer xenografts in mice. In summary, our results support OTUDin3 as a potent inhibitor of OTUD3, the inhibition of which may be a promising therapeutic strategy for NSCLC.

T-cell exhaustion signatures characterize the immune landscape and predict HCC prognosis via integrating single-cell RNA-seq and bulk RNA-sequencing.

Background: Hepatocellular carcinoma (HCC), the third most prevalent cause of cancer-related death, is a frequent primary liver cancer with a high rate of morbidity and mortality. T-cell depletion (TEX) is a progressive decline in T-cell function due to continuous stimulation of the TCR in the presence of sustained antigen exposure. Numerous studies have shown that TEX plays an essential role in the antitumor immune process and is significantly associated with patient prognosis. Hence, it is important to gain insight into the potential role of T cell depletion in the tumor microenvironment. The purpose of this study was to develop a trustworthy TEX-based signature using single-cell RNA-seq (scRNA-seq) and high-throughput RNA sequencing, opening up new avenues for evaluating the prognosis and immunotherapeutic response of HCC patients. Methods: The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) databases were used to download RNA-seq information for HCC patients. The 10x scRNA-seq. data of HCC were downloaded from GSE166635, and UMAP was used for clustering descending, and subgroup identification. TEX-related genes were identified by gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Afterward, we established a prognostic TEX signature using LASSO-Cox analysis. External validation was performed in the ICGC cohort. Immunotherapy response was assessed by the IMvigor210, GSE78220, GSE79671, and GSE91061cohorts. In addition, differences in mutational landscape and chemotherapy sensitivity between different risk groups were investigated. Finally, the differential expression of TEX genes was verified by qRT-PCR. Result: 11 TEX genes were thought to be highly predictive of the prognosis of HCC and substantially related to HCC prognosis. Patients in the low-risk group had a greater overall survival rate than those in the high-risk group, according to multivariate analysis, which also revealed that the model was an independent predictor of HCC. The predictive efficacy of columnar maps created from clinical features and risk scores was strong. Conclusion: TEX signature and column line plots showed good predictive performance, providing a new perspective for assessing pre-immune efficacy, which will be useful for future precision immuno-oncology studies.

[Bioinformatic analysis of the clinical significance of calneuron 1 (CALN1) in glioma and its correlation with immune cell infiltration].

Objective To analyze the clinical significance of calneuron 1 (CALN1) expression in glioma and its role in tumor immune cell infiltration by bioinformatics. Methods The expression of CALN1 gene in glioma in the Cancer Genome Atlas (TCGA) database was analyzed by Xiantao Academic Online. Kaplan-Meier survival analysis was used to evaluate its prognostic value, and receiver operating characteristic (ROC) curve was employed to evaluate its clinical diagnostic efficiency. Gene Set Enrichment Analysis (GSEA) was adopted to identify the potential mechanism of CALN1 in glioma. The relationship between CALN1 mRNA and glioma immune cell infiltration was discussed. Results The expression of CALN1 decreased significantly in glioma, and its expression level was negatively correlated with tumor grade. Compared with the control group, the expression level of CALN1 in isocitrate dehydrogenase mutant and 1p/19q co-deletion gliomas increased significantly. Glioma patients with low expression of CALN1 had poor prognosis and significantly reduced overall survival, disease specific survival and progression-free interval. ROC curve analysis showed that CALN1 expression level had good clinical diagnostic value. The results of GSEA gene enrichment suggested that the expression level of CALN1 was negatively correlated with mitosis and neutrophil degranulation. Immunoinfiltration analysis showed that T helper type 2 (Th2) cells, macrophages and neutrophils were significantly increased in the group with low expression of CALN1. Conclusion The expression level of CALN1 in glioma is positively correlated with the prognosis. The abnormal decrease of CALN1 expression may lead to the invasion of tumor-promoting immune cells. CALN1 can be used as a potential prognostic marker and therapeutic target for glioma.

Analysis of oil synthesis pathway in Cyperus esculentus tubers and identification of oleosin and caleosin genes.

The tubers of the widely distributed Cyperus esculentus are rich in oil, and therefore, the plant is considered to have a high utilization value in the vegetable oil industry. Oleosins and caleosins are lipid-associated proteins found in oil bodies of seeds; however oleosins and caleosins genes have not been identified in C. esculentus. In this study, we performed transcriptome sequencing and lipid metabolome analysis of C. esculentus tubers at four developmental stages to obtain the information on their genetic profile, expression trends, and metabolites in oil accumulation pathways. Overall, 120,881 non-redundant unigenes and 255 lipids were detected; 18 genes belonged to the acetyl-CoA carboxylase (ACC), malonyl-CoA:ACP transacylase (MCAT), ß-ketoacyl-ACP synthase (KAS), and fatty acyl-ACP thioesterase (FAT) gene families involved in fatty acid biosynthesis, and 16 genes belonged to the glycerol-3-phosphate acyltransferase (GPAT), diacylglycerol acyltransferase 3 (DGAT3), phospholipid:diacylglycerol acyltransferase (PDAT), FAD2, and lysophosphatidic acid acyltransferase (LPAAT) gene families playing important roles in triacylglycerol synthesis. We also identified 9 oleosin- and 21 caleosin-encoding genes in C. esculentus tubers. These results provide detailed information on the C. esculentus transcriptional and metabolic profiles, which can be used as reference for the development of strategies to increase oil content in C. esculentus tubers.

Circadian rhythm-related genes index: A predictor for HNSCC prognosis, immunotherapy efficacy, and chemosensitivity.

Background: Head and neck squamous cell carcinoma (HNSCC) is the most common head and neck cancer and is highly aggressive and heterogeneous, leading to variable prognosis and immunotherapy outcomes. Circadian rhythm alterations in tumourigenesis are of equal importance to genetic factors and several biologic clock genes are considered to be prognostic biomarkers for various cancers. The aim of this study was to establish reliable markers based on biologic clock genes, thus providing a new perspective for assessing immunotherapy response and prognosis in patients with HNSCC. Methods: We used 502 HNSCC samples and 44 normal samples from the TCGA-HNSCC dataset as the training set. 97 samples from GSE41613 were used as an external validation set. Prognostic characteristics of circadian rhythm-related genes (CRRGs) were established by Lasso, random forest and stepwise multifactorial Cox. Multivariate analysis revealed that CRRGs characteristics were independent predictors of HNSCC, with patients in the high-risk group having a worse prognosis than those in the low-risk group. The relevance of CRRGs to the immune microenvironment and immunotherapy was assessed by an integrated algorithm. Results: 6-CRRGs were considered to be strongly associated with HNSCC prognosis and a good predictor of HNSCC. The riskscore established by the 6-CRRG was found to be an independent prognostic factor for HNSCC in multifactorial analysis, with patients in the low-risk group having a higher overall survival (OS) than the high-risk group. Nomogram prediction maps constructed from clinical characteristics and riskscore had good prognostic power. Patients in the low-risk group had higher levels of immune infiltration and immune checkpoint expression and were more likely to benefit from immunotherapy. Conclusion: 6-CRRGs play a key predictive role for the prognosis of HNSCC patients and can guide physicians in selecting potential responders to prioritise immunotherapy, which could facilitate further research in precision immuno-oncology.

Identification of copper metabolism-related subtypes and establishment of the prognostic model in ovarian cancer.

Background: Ovarian cancer (OC) is one of the most common and most malignant gynecological malignancies in gynecology. On the other hand, dysregulation of copper metabolism (CM) is closely associated with tumourigenesis and progression. Here, we investigated the impact of genes associated with copper metabolism (CMRGs) on the prognosis of OC, discovered various CM clusters, and built a risk model to evaluate patient prognosis, immunological features, and therapy response. Methods: 15 CMRGs affecting the prognosis of OC patients were identified in The Cancer Genome Atlas (TCGA). Consensus Clustering was used to identify two CM clusters. lasso-cox methods were used to establish the copper metabolism-related gene prognostic signature (CMRGPS) based on differentially expressed genes in the two clusters. The GSE63885 cohort was used as an external validation cohort. Expression of CM risk score-associated genes was verified by single-cell sequencing and quantitative real-time PCR (qRT-PCR). Nomograms were used to visually depict the clinical value of CMRGPS. Differences in clinical traits, immune cell infiltration, and tumor mutational load (TMB) between risk groups were also extensively examined. Tumour Immune Dysfunction and Rejection (TIDE) and Immune Phenotype Score (IPS) were used to validate whether CMRGPS could predict response to immunotherapy in OC patients. Results: In the TCGA and GSE63885 cohorts, we identified two CM clusters that differed significantly in terms of overall survival (OS) and tumor microenvironment. We then created a CMRGPS containing 11 genes to predict overall survival and confirmed its reliable predictive power for OC patients. The expression of CM risk score-related genes was validated by qRT-PCR. Patients with OC were divided into low-risk (LR) and high-risk (HR) groups based on the median CM risk score, with better survival in the LR group. The 5-year AUC value reached 0.74. Enrichment analysis showed that the LR group was associated with tumor immune-related pathways. The results of TIDE and IPS showed a better response to immunotherapy in the LR group. Conclusion: Our study, therefore, provides a valuable tool to further guide clinical management and tailor the treatment of patients with OC, offering new insights into individualized treatment.

Light plays a critical role in the accumulation of chlorogenic acid in Lonicera macranthoides Hand.-Mazz.

Light has important effects on plant metabolism. However, the relationship between the chlorogenic acid (CGA) content and light in plants remains unclear. Here, we investigated the effects of shading treatment on gene expression and CGA content in Lonicera macranthoides Hand.-Mazz. (LM), a widely used medicinal plant. A total of 1891 differentially expressed genes (DEGs) were obtained in flower buds and 819 in leaves in response to light in shading treatment compared to the control sample by RNA-Seq. After shading treatment, the content of CGA in LM leaves decreased significantly by 1.78-fold, the carotenoid content increased, and the soluble sugar and starch contents significantly decreased. WGCNA and the expression of related genes verified by qRT‒PCR revealed that CGA synthesis pathway enzyme genes form a co-expression network with genes for carbohydrate synthesis, photosynthesis, light signalling elements, and transcription factor genes (TFs) that affect the accumulation of CGA. Through a virus-induced gene silencing (VIGS) system and CGA assay in Nicotiana benthamiana (NB), we determined that downregulation of NbHY5 expression decreased the CGA content in NB leaves. In this study, we found that light provides energy and material for the accumulation of CGA in LM, and light affects the expression of CGA accumulation-related genes. Our results show that different light intensities have multiple effects on leaves and flower buds in LM and are able to coregulate LmHY5 expression and CGA synthesis.

An Aggrephagy-Related LncRNA Signature for the Prognosis of Pancreatic Adenocarcinoma.

Pancreatic adenocarcinoma (PAAD) is a common, highly malignant, and aggressive gastrointestinal tumor. The conventional treatment of PAAD shows poor results, and patients have poor prognosis. The synthesis and degradation of proteins are essential for the occurrence and development of tumors. Aggrephagy is a type of autophagy that selectively degrades aggregated proteins. It decreases the formation of aggregates by degrading proteins, thus reducing the harm to cells. By breaking down proteins, it decreases the formation of aggregates; thus, minimizing damage to cells. For evaluating the response to immunotherapy and prognosis in PAAD patients, in this study, we developed a reliable signature based on aggrephagy-related genes (ARGs). We obtained 298 AGGLncRNAs. Based on the results of one-way Cox and LASSO analyses, the lncRNA signature was constructed. In the risk model, the prognosis of patients in the low-risk group was noticeably better than that of the patients in the high-risk group. Additionally, the ROC curves and nomograms validated the capacity of the risk model to predict the prognosis of PAAD. The patients in the low-risk and high-risk groups showed considerable variations in functional enrichment and immunological analysis. Regarding drug sensitivity, the low-risk and high-risk groups had different half-maximal inhibitory concentrations (IC50).

PDPN contributes to constructing immunosuppressive microenvironment in IDH wildtype glioma.

The tumor immunosuppressive microenvironment (IME) significantly affects tumor occurrence, progression, and prognosis, but the underlying molecular mechanisms remain to make known. We investigated the prognostic significance of PDPN and its role in IME in glioma. Weighted gene co-expression network analysis (WGCNA) found PDPN closely related to IDH wildtype status and higher immune score. Correlation analysis suggested PDPN was highly positively relevant to immune checkpoints expression and immune checkpoints block responding status. Correlation analysis together with verification in vitro suggested PDPN highly positively relevant tumor-associated neutrophils (TANs) and tumor-associated macrophages (TAMs). Least absolute shrinkage and selection operator (LASSO) regression employed to develop the prediction model with TANs and TAMs markers showed that high risk scores predicted worse prognosis. We highlight that PDPN overexpression is an independent prognostic indicator, and promotes macrophage M2 polarization and neutrophil degranulation, ultimately devotes to the formation of an immunosuppressive tumor microenvironment. Our findings contribute to re-recognizing the role of PDPN in IDH wildtype gliomas and implicate promising target therapy combined with immunotherapy for this highly malignant tumor.

Elucidating the Influence of MPT-driven necrosis-linked LncRNAs on immunotherapy outcomes, sensitivity to chemotherapy, and mechanisms of cell death in clear cell renal carcinoma.

Background: Clear cell renal carcinoma (ccRCC) stands as the prevailing subtype among kidney cancers, making it one of the most prevalent malignancies characterized by significant mortality rates. Notably,mitochondrial permeability transition drives necrosis (MPT-Driven Necrosis) emerges as a form of cell death triggered by alterations in the intracellular microenvironment. MPT-Driven Necrosis, recognized as a distinctive type of programmed cell death. Despite the association of MPT-Driven Necrosis programmed-cell-death-related lncRNAs (MPTDNLs) with ccRCC, their precise functions within the tumor microenvironment and prognostic implications remain poorly understood. Therefore, this study aimed to develop a novel prognostic model that enhances prognostic predictions for ccRCC. Methods: Employing both univariate Cox proportional hazards and Lasso regression methodologies, this investigation distinguished genes with differential expression that are intimately linked to prognosis.Furthermore, a comprehensive prognostic risk assessment model was established using multiple Cox proportional hazards regression. Additionally, a thorough evaluation was conducted to explore the associations between the characteristics of MPTDNLs and clinicopathological features, tumor microenvironment, and chemotherapy sensitivity, thereby providing insights into their interconnectedness.The model constructed based on the signatures of MPTDNLs was verified to exhibit excellent prediction performance by Cell Culture and Transient Transfection, Transwell and other experiments. Results: By analyzing relevant studies, we identified risk scores derived from MPTDNLs as an independent prognostic determinant for ccRCC, and subsequently we developed a Nomogram prediction model that combines clinical features and associated risk assessment. Finally, the application of experimental techniques such as qRT-PCR helped to compare the expression of MPTDNLs in healthy tissues and tumor samples, as well as their role in the proliferation and migration of renal clear cell carcinoma cells. It was found that there was a significant correlation between CDK6-AS1 and ccRCC results, and CDK6-AS1 plays a key role in the proliferation and migration of ccRCC cells. Impressive predictive results were generated using marker constructs based on these MPTDNLs. Conclusions: In this research, we formulated a new prognostic framework for ccRCC, integrating mitochondrial permeability transition-induced necrosis. This model holds significant potential for enhancing prognostic predictions in ccRCC patients and establishing a foundation for optimizing therapeutic strategies.

Machine learning to construct sphingolipid metabolism genes signature to characterize the immune landscape and prognosis of patients with uveal melanoma.

Background: Uveal melanoma (UVM) is the most common primary intraocular malignancy in adults and is highly metastatic, resulting in a poor patient prognosis. Sphingolipid metabolism plays an important role in tumor development, diagnosis, and prognosis. This study aimed to establish a reliable signature based on sphingolipid metabolism genes (SMGs), thus providing a new perspective for assessing immunotherapy response and prognosis in patients with UVM. Methods: In this study, SMGs were used to classify UVM from the TCGA-UVM and GEO cohorts. Genes significantly associated with prognosis in UVM patients were screened using univariate cox regression analysis. The most significantly characterized genes were obtained by machine learning, and 4-SMGs prognosis signature was constructed by stepwise multifactorial cox. External validation was performed in the GSE84976 cohort. The level of immune infiltration of 4-SMGs in high- and low-risk patients was analyzed by platforms such as CIBERSORT. The prediction of 4-SMGs on immunotherapy and immune checkpoint blockade (ICB) response in UVM patients was assessed by ImmuCellAI and TIP portals. Results: 4-SMGs were considered to be strongly associated with the prognosis of UVM and were good predictors of UVM prognosis. Multivariate analysis found that the model was an independent predictor of UVM, with patients in the low-risk group having higher overall survival than those in the high-risk group. The nomogram constructed from clinical characteristics and risk scores had good prognostic power. The high-risk group showed better results when receiving immunotherapy. Conclusions: 4-SMGs signature and nomogram showed excellent predictive performance and provided a new perspective for assessing pre-immune efficacy, which will facilitate future precision immuno-oncology studies.