Comprehensive investigation of RNA‐sequencing dataset reveals the hub genes and molecular mechanisms of coronavirus disease 2019 acute respiratory distress syndrome

The goal of this study is to reveal the hub genes and molecular mechanisms of the coronavirus disease 2019 (COVID‐19) acute respiratory distress syndrome (ARDS) based on the genome‐wide RNA sequencing dataset. The RNA sequencing dataset of COVID‐19 ARDS was obtained from {"type":"entrez-geo","attrs":{"text":"GSE163426","term_id":"163426"}}GSE163426. A total of 270 differentially expressed genes (DEGs) were identified between COVID‐19 ARDS and control group patients. Functional enrichment analysis of DEGs suggests that these DEGs may be involved in the following biological processes: response to cytokine, G‐protein coupled receptor activity, ionotropic glutamate receptor signalling pathway and G‐protein coupled receptor signalling pathway. By using the weighted correlation network analysis approach to analyse these DEGs, 10 hub DEGs that may play an important role in COVID‐19 ARDS were identified. A total of 67 potential COVID‐19 ARDS targetted drugs were identified by a complement map analysis. Immune cell infiltration analysis revealed that the levels of T cells CD4 naive, T cells follicular helper, macrophages M1 and eosinophils in COVID‐19 ARDS patients were significantly different from those in control group patients. In conclusion, this study identified 10 COVID‐19 ARDS‐related hub DEGs and numerous potential molecular mechanisms through a comprehensive analysis of the RNA sequencing dataset and also revealed the difference in immune cell infiltration of COVID‐19 ARDS.     

Design and implementation of an adaptive fuzzy sliding mode controller for drug delivery in treatment of vascular cancer tumours and its optimisation using genetic algorithm tool

In this paper, the side effects of drug therapy in the process of cancer treatment are reduced by designing two optimal non‐linear controllers. The related gains of the designed controllers are optimised using genetic algorithm and simultaneously are adapted by employing the Fuzzy scheduling method. The cancer dynamic model is extracted with five differential equations, including normal cells, endothelial cells, cancer cells, and the amount of two chemotherapy and anti‐angiogenic drugs left in the body as the engaged state variables, while double drug injection is considered as the corresponding controlling signals of the mentioned state space. This treatment aims to reduce the tumour cells by providing a timely schedule for drug dosage. In chemotherapy, not only the cancer cells are killed but also other healthy cells will be destroyed, so the rate of drug injection is highly significant. It is shown that the simultaneous application of chemotherapy and anti‐angiogenic therapy is more efficient than single chemotherapy. Two different non‐linear controllers are employed and their performances are compared. Simulation results and comparison studies show that not only adding the anti‐angiogenic reduce the side effects of chemotherapy but also the proposed robust controller of sliding mode provides a faster and stronger treatment in the presence of patient parametric uncertainties in an optimal way. As a result of the proposed closed‐loop drug treatment, the tumour cells rapidly decrease to zero, while the normal cells remain healthy simultaneously. Also, the injection rate of the chemotherapy drug is very low after a short time and converges to zero.     

Solvent effect in the synthesis of hydrophobic drug‐loaded polymer nanoparticles

Quercetin is an abundant flavonoid in fruits, vegetables such as onion, tea leaves, cranberry, radish leaves etc. with numerous biological activities and widely used as an effective antioxidant. Its low solubility in water and chemical decomposition in intestinal environment are predicaments in delivery through dietary or oral intake. Noble polymeric nanoparticles are of particular interest today because of their applications in many areas. Polymer nanoparticles have attracted the interest of many research groups and have been utilised in an increasing number of fields such as site targeted drug delivery in cancer research during the last decades. Various techniques can be used to produce polymer nanoparticles, such as solvent evaporation, salting‐out, dialysis, supercritical fluid technology etc. The choice of method depends on a number of factors, such as, particle size, particle size distribution, area of application, etc. In the present study, single emulsion‐solvent evaporation technique has been utilised with two different organic solvents: acetone and chloroform/methanol to prepare quercetin loaded poly(D,L‐lactide‐co‐glycolide) nanoparticles. According to the authors’ observations acetone is a better solvent for encapsulating quercetin in polymer nanoparticles owing to its physical and chemical properties.Inspec keywords: solvent effects, nanofabrication, nanomedicine, nanoparticles, hydrophobicity, cancer, drug delivery systems, emulsions, evaporationOther keywords: particle size, single emulsion‐solvent evaporation technique, acetone, chloroform/methanol, cancer research, drug delivery, antioxidant, flavonoid, quercetin, hydrophobic drug‐loaded polymer nanoparticles, nanoparticle synthesis, solvent effect     

In‐vitro and in‐vivo evaluation of chitosan‐based thermosensitive gel containing lorazepam NLCs for the treatment of status epilepticus

The objective of this study was to develop an in‐situ gel containing lorazepam (LZM) loaded nanostructured lipid carriers (NLCs) for direct nose‐to‐brain delivery in order to increase drug therapeutic efficacy in the treatment of epilepsy. Accordingly, LZM loaded NLCs were formulated using emulsification solvent diffusion and evaporation method; then the effects of the formulation variables on different physicochemical characteristics of NLCs were investigated. Thermosensitive in‐situ gels containing LZM‐NLCs were prepared using a combination of chitosan and β‐glycerol phosphate (β‐GP). The anticonvulsant efficacy of LZM‐NLCs‐Gel was then examined using the pentylenetetrazole (PTZ) model. The optimised NLCs were spherical, showing the particle size of 71.70 ± 5.16 nm and the zeta potential of −20.06 ± 2.70 mV. The pH and gelation time for the chitosan solution with 15% (w/v) β‐GP were determined to be 7.12 ± 0.03 and 5.33 ± 0.58 min, respectively. The in‐vivo findings showed that compared with the control group and the group that received LZM‐Gel, the occurrence of PTZ‐induced seizures in the rats was significantly reduced by LZM‐NLCs‐Gel after intranasal administration. These results, therefore, suggested that the LZM‐NLCs‐Gel system could have potential applications for brain targeting through nasal route and might increase LZM therapeutic efficacy in the treatment of epilepsy.Inspec keywords: biomedical materials, nanomedicine, cellular biophysics, electrokinetic effects, drug delivery systems, nanoparticles, brain, pH, drugs, particle size, nanofabrication, medical disorders, polymer gelsOther keywords: evaporation method, β‐glycerol phosphate, β‐GP, optimised NLCs, received LZM‐Gel, LZM therapeutic efficacy, chitosan‐based thermosensitive gel, lorazepam NLCs, nose‐to‐brain delivery, drug therapeutic efficacy, emulsification solvent diffusion, in‐vivo evaluation, in‐vitro evaluation, LZM‐NLC‐gel system, status epilepticus treatment, lorazepam loaded nanostructured lipid carriers, epilepsy treatment, physicochemical characteristics, thermosensitive in‐situ gel, anticonvulsant efficacy, pentylenetetrazole model, particle size, zeta potential, pH, gelation time, chitosan solution, PTZ‐induced seizures, intranasal administration     

Dynamic optimal experimental design yields marginal improvement over steady‐state results for computational maximisation of regulatory T‐cell induction in ex vivo culture

The isolation of T cells, followed by differentiation into Regulatory T cells (Tregs), and re‐transplantation into the body has been proposed as a therapeutic option for inflammatory bowel disease. A key requirement for making this a viable therapeutic option is the generation of a large population of Tregs. However, cytokines in the local microenvironment can impact the yield of Tregs during differentiation. As such, experimental design is an essential part of evaluating the importance of different cytokine concentrations for Treg differentiation. However, currently only single, constant concentrations of the cytokines have been investigated. This work addresses this point by performing experimental design in silico which seeks to maximize the predicted induction of Tregs relative to Th17 cells, by selecting an optimal input function for the concentrations of TGF‐β, IL‐2, IL‐6, and IL‐23. While this approach sounds promising, the results show that only marginal improvements in the concentration of Tregs can be achieved for dynamic cytokine profiles as compared to optimal constant concentrations. Since constant concentrations are easier to implement in experiments, it is recommended for this particular system to keep the concentrations constant where IL‐6 should be kept low and high concentrations of TGF‐β, IL‐2, and IL‐23 should be used.Inspec keywords: patient treatment, molecular biophysics, proteins, cellular biophysics, diseasesOther keywords: Tregs relative, optimal input function, dynamic cytokine profiles, optimal constant concentrations, IL‐23, computational maximisation, regulatory T‐cell induction, inflammatory bowel disease, viable therapeutic option, local microenvironment, Treg differentiation, single concentrations, predicted induction, dynamic optimal experimental design, interleukin‐2, IL‐6, transforming growth factor‐β     

Functional role of microRNA‐500a‐3P‐loaded liposomes in the treatment of cisplatin‐induced AKI

Cisplatin treatment results in acute kidney injury (AKI) by the phosphorylation of mixed lineage kinase domain‐like protein (MLKL). The knockout of MLKL, which is a principle mediator of necroptosis, is believed to alleviate the AKI symptoms. The present study was aimed to improve the therapeutic efficacy in AKI. For this purpose, miR‐500a‐3P was identified as appropriate miRNA therapeutics and loaded in liposome delivery carrier. The authors have showed that the miR‐LIP directly controls the expression of RIPK3 and MLKL – a modulator of necroptosis and thereby reduces the severity of kidney injury. The miR‐LIP significantly controlled the phosphorylation of MLKL compared to that of CDDP‐treated HK2 cells. Similar results are observed with RIPK3. The miR‐LIP has also been demonstrated to control the inflammatory response in tubular cells. Western blot analysis further revealed that the phosphorylation of P‐65 was mainly responsible for the inflammatory response and miR‐LIP significantly decreased the CDDP‐induced NF‐kB phosphorylation. Overall, the present study explored the molecular mechanism behind the necroptosis in AKI and potential of miRNA in targeting MLKL pathways. Study further highlights the potential advantage of liposome as a delivery carrier for miRNA therapeutics.Inspec keywords: medical disorders, biochemistry, cancer, cellular biophysics, kidney, enzymes, drugs, toxicology, patient treatment, injuries, genetics, molecular biophysicsOther keywords: current 500.0 A, functional role, microRNA‐500a‐3P‐loaded liposomes, cisplatin‐induced AKI, cisplatin treatment results, acute kidney injury, phosphorylation, mixed lineage kinase domain, necroptosis, AKI symptoms, therapeutic efficacy, appropriate miRNA therapeutics, liposome delivery carrier, miR‐LIP, RIPK3, inflammatory response, CDDP‐induced NF‐kB, MLKL pathways     

Synthesis and characterisation of neem leaf extract, 2, 3‐dehydrosalanol and quercetin dihydrate mediated silver nano particles for therapeutic applications

The utility of green silver nanoparticles (AgNPs) in veterinary medicine is steadily increasing as they have many therapeutic applications against pathogens and arthropods of livestock. In this study, green AgNPs using neem (N‐AgNPs), 2,3‐dehydrosalanol (2,3‐DHS‐AgNPs) and quercetin dihydrate (QDH‐AgNPs) were synthesised and characterised. Synthesised compounds were characterised by UV‐Vis spectroscopy and the peak absorbance was recorded at 370 nm for neem extract. For N‐AgNPs, 2,3‐DHS‐AgNPs and QDH‐AgNPs, the maximum absorbance peaks were at 430, 230 and 220 nm, respectively. The FTIR analysis confirmed the synthesis of green AgNPs. The XRD pattern of N‐AgNPs showed the peaks corresponding to whole spectra of 2 θ values ranging from 10–80. The relatively higher intensity of (111, 222) planes in face centred cubic crystalline structure supports the formation of synthesised AgNPs. In DLS analysis, the hydrodynamic diameter of neem leaf extract was found to be 259.8 nm, followed by 5.3, 6.7 and 261.8 nm for 2,3‐DHS‐AgNPs, N‐AgNPs and QDH‐AgNPs, respectively. Based on the transmission electron microscopy and scanning electron microscopy image analyses, confirmed the formation of N‐AgNPs, 2,3‐DHS‐AgNPs and QDH‐AgNPs. These eco‐friendly phyto‐AgNPs may be of use as an effective alternative to chemical control methods against the arthropods of livestock.Inspec keywords: nanoparticles, silver, nanomedicine, biomedical materials, nanofabrication, Fourier transform infrared spectra, ultraviolet spectra, visible spectra, X‐ray diffraction, light scattering, transmission electron microscopy, scanning electron microscopy, aggregation, veterinary medicineOther keywords: 2,3‐dehydrosalanol mediated silver nanoparticles, quercetin dihydrate mediated silver nanoparticles, therapeutic applications, green silver nanoparticles, veterinary medicine, Azadirachta indica, UV‐visible spectroscopy, Fourier transformed infrared analysis, X‐ray diffraction, (111) planes, (222) planes, face centred cubic crystalline structure, dynamic light scattering, hydrodynamic diameter, aqueous neem leaf extract, transmission electron microscopy, hexagonal shape, pencil head shape, cuboid shape, scanning electron microscopy, aggregation, arthropod infesting livestock, Ag, in‐vivo antiectoparasitic activity, in‐vitro antiectoparasitic activity     

Identification and analysis of circRNA–miRNA–mRNA regulatory network in hepatocellular carcinoma

This study was to identify important circRNA–miRNA–mRNA (ceRNAs) regulatory mechanisms in hepatocellular carcinoma (HCC). The circRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE97332","term_id":"97332"}}GSE97332 and miRNA dataset {"type":"entrez-geo","attrs":{"text":"GSE57555","term_id":"57555"}}GSE57555 were used for analyses. Functional enrichment analysis for miRNA and target gene was conducted using cluster Profiler. Survival analysis was conducted through R package Survival. The ceRNAs and drug–gene interaction networks were constructed. The ceRNAs network contained five miRNAs including hsa‐miR‐25‐3p, hsa‐miR‐3692‐5p, hsa‐miR‐4270, hsa‐miR‐331‐3p, and hsa‐miR‐125a‐3p. Among the network, hsa‐miR‐25‐3p targeted the most genes, hsa‐miR‐3692‐5p and hsa‐miR‐4270 were targeted by more circRNAs than other miRNAs, hsa‐circ‐0034326 and hsa‐circ‐0011950 interacted with three miRNAs. Furthermore, target genes, including NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were obtained in drug–gene interaction network. Survival analysis showed NRAS, ITGA5, SLC7A1, SEC14L2, SLC12A5, and SMAD2 were significantly associated with prognosis of HCC. NRAS, ITGA5, and SMAD2 were significantly enriched in proteoglycans in cancer. Moreover, hsa‐circ‐0034326 and hsa‐circ‐0011950 might function as ceRNAs to play key roles in HCC. Furthermore, miR‐25‐3p, miR‐3692‐5p, and miR‐4270 might be significant for HCC development. NRAS, ITGA5, SEC14L2, SLC12A5, and SMAD2 might be prognostic factors for HCC patients via proteoglycans in cancer pathway. Taken together, the findings will provide novel insight into pathogenesis, selection of therapeutic targets and prognostic factors for HCC.Inspec keywords: cancer, cellular biophysics, patient diagnosis, bioinformatics, tumours, biochemistry, molecular biophysics, genetics, drugs, RNAOther keywords: ITGA5, SMAD2, hsa‐circ‐0034326, SEC14L2, SLC12A5, target gene, survival analysis, drug–gene interaction network, miRNAs, hsa‐miR‐25‐3p, hsa‐miR‐3692‐5p, hsa‐miR‐4270, hsa‐miR‐331‐3p, hsa‐miR‐125a‐3p, hsa‐circ‐0011950, SLC7A1, pathogenesis, therapeutic targets, prognostic factors, circRNA‐miRNA‐mRNA regulatory network, current 125.0 A     

Fabrication of microcapsules with core‐shell structure for oral delivery of dual drugs and real‐time computed tomography imaging

Although multidrug combinations are an effective therapeutic strategy for serious disease in clinical practice, their therapeutic effect may be reduced because they conflict with each other medicinally in certain cases. Hence, there is an urgent need to develop a single drug carrier for precise multidrug delivery to avoid this interference. A reverse coordination method is reported that fabricates a double‐layer barium sulphate microcapsule (DL@BS MS) for two drugs separately loading simultaneously. In addition, BS nanoclusters were synthesised in situ inside the DL@BS MSs for real‐time computed tomography (CT) imaging. The results showed that the DL@BS MSs with a particle size of approximately 2 mm exhibited a uniform sphere. Because BS nanoclusters have a high X‐ray attenuation coefficient, the retention of DL@BS MSs in the digestive tract could be monitored through CT imaging in real time. More important, the core‐shell structure of DL@BS MSs encapsulating two different drugs could be released in spatiotemporal order in an acidic stomach environment. The as‐synthesis DL@BS MSs with a core‐shell structure and real‐time imaging performance provide an ideal carrier for the oral administration of multiple drugs simultaneously loaded but sequentially released.     

Metal nanoparticles synthesis through natural phenolic acids

For being applied in medicine as therapeutic agents, nanostructures need to be biocompatible and eco‐friendly. Plant‐derived phenolic acids have been utilised for green synthesis of metallic or metallic oxide nanoparticles (NPs). The phenolic acids play role as both reducing agents and stabilisers in the process of NPs synthesis. Many experiments have been dedicated to develop efficient green synthesis techniques for producing metal NPs. Using phenolic acids represents a reproducible, simple, profitable, and cost‐effective strategy to synthesise metal NPs. As a phytochemical for metal NPs synthesis, phenolic acids are antioxidants that represent many health benefits. However, limited studies have been dedicated to the synthesis and characterisation of NPs produced by phenolic acids. Thus, this review focused on phenolic acids mediated nanomaterial synthesis and its biomedical applications. It should be noted the mechanism of metal ion bioreduction, phenolic acids surface adsorption, characterisation, and toxicity of metal NPs made with different phenolic acids have been discussed in this review.Inspec keywords: bio‐inspired materials, organic compounds, adsorption, nanofabrication, nanoparticles, biomedical materials, nanomedicineOther keywords: toxicity, biomedical applications, antioxidants, phytochemical synthesis, reducing agents, therapeutic agents, medicine, metallic oxide nanoparticles, plant‐derived phenolic acids, natural phenolic acids, metal nanoparticles synthesis, phenolic acids surface adsorption, metal ion bioreduction, nanomaterial synthesis, efficient green synthesis techniques     

Mn‐doped ZnS quantum dots‐chlorin e6 shows potential as a treatment for chondrosarcoma: an in vitro study

Chondrosarcoma is the second‐most malignant cancer of the bone and routine treatments such as chemotherapy and radiotherapy have not responded to the treatment of this cancer. Due to the resistance of chondrosarcoma to radiotherapy, the combination of therapeutic methods has been considered in recent years. In this study, a novel combination approach is used that allows photodynamic therapy to be activated by X‐rays. The synthesis of Mn‐doped zinc sulphide (ZnS) quantum dots was carried out and chlorin e6 photosensitiser attached by covalent and non‐covalent methods and their application as an intracellular light source for photodynamic activation was investigated. The toxicity of each nanoparticles was evaluated on chondrosarcoma cancer cells (SW1353) before and after radiation. Also, the effect nanoparticle‐photosensitiser conjugated type was investigated in the therapeutic efficacy. The characterisation test (SEM, TEM, EDS, TGA, XRD and ICP analyses) was shown successful synthesis of Mn‐doped ZnS quantum dots. Chondrosarcoma cancer cell viability was significantly reduced when cells were treated with MPA‐capped Mn‐doped ZnS quantum dots‐chlorin e6 with spermine linker and with covalent attachment (P  ≤ 0.001). These results indicate that X‐ray can activate the quantum dot complexes for cancer treatment, which can be a novel method for treatment of chondrosarcoma.Inspec keywords: semiconductor quantum dots, X‐ray diffraction, transmission electron microscopy, cadmium compounds, cellular biophysics, drugs, manganese, biomedical materials, cancer, quantum dots, nanofabrication, ultraviolet spectra, zinc compounds, fluorescence, scanning electron microscopy, nanoparticles, nanomedicine, bone, photochemistry, photodynamic therapy, tumours, II‐VI semiconductors, laser applications in medicineOther keywords: noncovalent methods, photodynamic activation, chondrosarcoma cancer cells, chondrosarcoma cancer cell viability, quantum dot complexes, cancer treatment, malignant cancer, routine treatments, radiotherapy, therapeutic methods, Mn‐doped zinc sulphide quantum dots, in vitro study, MPA‐capped Mn‐doped ZnS quantum dots‐chlorin e6, nanoparticle‐photosensitiser conjugated type, ZnS, Mn, ZnS:Mn     

Polyethylenimine‐modified curcumin‐loaded mesoporus silica nanoparticle (MCM‐41) induces cell death in MCF‐7 cell line

Breast cancer accounts for the first highest mortality rate in India and second in world. Though current treatment strategies are effectively killing cancer cells, they also end in causing severe side effects and drug resistance. Curcumin is a nutraceutical with multipotent activity but its insolubility in water limits its therapeutic potential as an anti‐cancer drug. The hydrophilicity of curcumin could be increased by nanoformulation or changing its functional groups. In this study, curcumin is loaded on mesoporous silica nanoparticle and its anti‐cancer activity is elucidated with MCF‐7 cell death. Structural characteristics of Mobil Composition of Matter ‐ 41(MCM‐41) as determined by high‐resolution transmission electron microscopy (HR‐TEM) shows that MCM‐41 size ranges from 100 to 200 nm diameters with pore size 2–10 nm for drug adsorption. The authors found 80–90% of curcumin is loaded on MCM‐41 and curcumin is released efficiently at pH 3.0. The 50 µM curcumin‐loaded MCM‐41 induced 50% mortality of MCF‐7 cells. Altogether, their results suggested that increased curcumin loading and sustained release from MCM‐41 effectively decreased cell survival of MCF‐7 cells in vitro.Inspec keywords: cancer, cellular biophysics, nanoparticles, nanomedicine, biomedical materials, polymers, mesoporous materials, transmission electron microscopy, drugs, adsorptionOther keywords: polyethylenimine‐modified curcumin‐loaded mesoporus silica nanoparticle, MCF‐7 cell line, breast cancer, cancer cells, drug resistance, multipotent activity, therapeutic potential, anticancer drug, mesoporous silica nanoparticle, MCF‐7 cell death, high‐resolution transmission electron microscopy, drug adsorption, curcumin‐loaded MCM‐41, nutraceutical curcumin, size 2 nm to 10 nm, size 100 nm to 200 nm     

Effects of silver nanoparticles coated with anti‐HER2 on irradiation efficiency of SKBR3 breast cancer cells

Breast cancer is the second cause of death in the world. Ionising radiation is a potent mutagen that can cause DNA damage, chromosomes breakage, and cell death. In the present study, radiotherapy and nanoparticle‐antibodies (ABs) have been combined to enhance the efficacy of cancer cell treatment. Silver nanoparticles (SNP) were synthesised, coated with anti‐HER2, and then characterised with different techniques such as X‐ray diffraction, dynamic light scattering, transmission electron microscopy, Fourier transform infrared, and UV–Vis spectroscopy. SKBR3 cells were irradiated with cobalt‐60 in the presence of nanoparticle‐AB as the drug. Cell viability was measured using the diphenyltetrazolium bromide assay, and the cellular status was assessed by Raman spectroscopy. Irradiation considerably decreased cell viability proportionate to the dose increase and post‐irradiation time. The surface‐enhanced Raman spectroscopy increased the signal in the presence of SNP. Increasing the dose to 2 Gy increased the irradiation resistance, and higher dose increases (4 and 6 Gy) enhanced the irradiation sensitivity. Moreover, the cellular changes induced by irradiation in the presence of the drug were stable after 48 h. The authors results introduced the combination of the drug with radiation as an effective treatment for cancer and Raman spectroscopy as a suitable tool to diagnose effective irradiation doses.Inspec keywords: ultraviolet spectra, X‐ray diffraction, tumours, nanofabrication, silver, cellular biophysics, nanomedicine, cancer, drugs, DNA, light scattering, toxicology, biomagnetism, radiation therapy, Raman spectra, transmission electron microscopy, infrared spectra, nanoparticles, gynaecologyOther keywords: higher dose increases, irradiation sensitivity, drug, effective treatment, effective irradiation doses, silver nanoparticles, irradiation efficiency, SKBR3 breast cancer cells, ionising radiation, potent mutagen, DNA damage, cell death, nanoparticle‐antibodies, cancer cell treatment, SNP, different techniques, X‐ray diffraction, dynamic light scattering, transmission electron microscopy, UV–Vis spectroscopy, SKBR3 cells, nanoparticle‐AB, diphenyltetrazolium bromide assay, cell viability proportionate, dose increase, post‐irradiation time, surface‐enhanced Raman spectroscopy, irradiation resistance, time 48.0 hour, size 60.0 inch, Ag     

RYR2 mutation in non‐small cell lung cancer prolongs survival via down‐regulation of DKK1 and up‐regulation of GS1‐115G20.1: A weighted gene Co‐expression network analysis and risk prognostic models

RYR2 mutation is clinically frequent in non‐small cell lung cancer (NSCLC) with its function being elusive. We downloaded lung squamous cell carcinoma and lung adenocarcinoma samples from the TCGA database, split the samples into RYR2 mutant group (n = 337) and RYR2 wild group (n = 634), and established Kaplan‐Meier curves. The results showed that RYR2 mutant group lived longer than the wild group (p = 0.027). Weighted gene co‐expression network analysis (WGCNA) of differentially expressed genes (DEGs) yielded prognosis‐related genes. Five mRNAs and 10 lncRNAs were selected to build survival prognostic models with other clinical features. The AUCs of 2 models are 0.622 and 0.565 for predicting survival at 3 years. Among these genes, the AUCs of DKK1 and GS1‐115G20.1 expression levels were 0.607 and 0.560, respectively, which predicted the 3‐year survival rate of NSCLC sufferers. GSEA identified an association of high DKK1 expression with TP53, MTOR, and VEGF expression. Several target miRNAs interacting with GS1‐115G20.1 were observed to show the relationship with the phenotype, treatment, and survival of NSCLC. NSCLC patients with RYR2 mutation may obtain better prognosis by down‐regulating DKK1 and up‐regulating GS1‐115G20.1.