Application and advances of biomimetic membrane materials in central nervous system disorders.

Central nervous system (CNS) diseases encompass spinal cord injuries, brain tumors, neurodegenerative diseases, and ischemic strokes. Recently, there has been a growing global recognition of CNS disorders as a leading cause of disability and death in humans and the second most common cause of death worldwide. The global burdens and treatment challenges posed by CNS disorders are particularly significant in the context of a rapidly expanding global population and aging demographics. The blood-brain barrier (BBB) presents a challenge for effective drug delivery in CNS disorders, as conventional drugs often have limited penetration into the brain. Advances in biomimetic membrane nanomaterials technology have shown promise in enhancing drug delivery for various CNS disorders, leveraging properties such as natural biological surfaces, high biocompatibility and biosafety. This review discusses recent developments in biomimetic membrane materials, summarizes the types and preparation methods of these materials, analyzes their applications in treating CNS injuries, and provides insights into the future prospects and limitations of biomimetic membrane materials.

A novel prognostic signature based on smoking-associated genes for predicting prognosis and immune microenvironment in NSCLC smokers.

BACKGROUND: As a highly heterogeneous tumor, non-small cell lung cancer (NSCLC) is famous for its high incidence and mortality worldwide. Smoking can cause genetic changes, which leading to the occurrence and progress of NSCLC. Nevertheless, the function of smoking-related genes in NSCLC needs more research. METHODS: We downloaded transcriptome data and clinicopathological parameters from Gene Expression Omnibus (GEO) databases, and screened smoking-related genes. Lasso regression were applied to establish the 7-gene signature. The associations between the 7-gene signature and immune microenvironment analysis, survival analysis, drug sensitivity analysis and enriched molecular pathways were studied. Ultimately, cell function experiments were conducted to research the function of FCGBP in NSCLC. RESULTS: Through 7-gene signature, NSCLC samples were classified into high-risk group (HRG) and low-risk group (LRG). Significant difference in overall survival (OS) between HRG and LRG was found. Nomograms and ROC curves indicated that the 7-gene signature has a stable ability in predicting prognosis. Through the analysis of immune microenvironment, we found that LRG patients had better tumor immune activation. FCGBP showed the highest mutation frequency among the seven prognostic smoking related genes (LRRC31, HPGD, FCGBP, SPINK5, CYP24A1, S100P and FGG), and was notable down-regulated in NSCLC smokers compared with non-smoking NSCLC patients. The cell experiments confirmed that FCGBP knockdown promoting proliferation, migration, and invasion in NSCLC cells. CONCLUSION: This smoking-related prognostic signature represents a promising tool for assessing prognosis and tumor microenvironment in smokers with NSCLC. The role of FCGBP in NSCLC was found by cell experiments, which can be served as diagnostic biomarker and immunotherapy target for NSCLC.

Inhibition of urethral stricture by a catheter loaded with nanoparticle/ pirfenidone complexes.

Background: Urethral strictures are common injurious conditions of the urinary system. Reducing and preventing urethral strictures has become a hot and challenging topic for urological surgeons and related researchers. In this study, we developed a catheter loaded with nanoparticle/pirfenidone (NP/PFD) complexes and evaluated its effectiveness at inhibiting urethral stricture in rabbits, providing more references for the clinical prevention and reduction of urethral stenosis. Methods: Twelve adult male New Zealand rabbits were selected and divided into the following four groups in a ratio of 1:1:1:1 using the random number table method: Group A, sham; Group B, urethral stricture (US); Group C, US + unmodified catheter; and Group D, US + NP/PFD catheter. On the 30th day after modelling, retrograde urethrography was performed to evaluate urethral stricture formation, and histopathological examination was performed on the tissues of the corresponding surgical site. Meanwhile, changes in the expression level of Transforming growth factor ß1 (TGF-ß1) in the tissues were detected by immunohistochemistry. Results: The NP/PFD complexes adhered uniformly to the catheter surface. They remained on the surface of the catheter after insertion into the urethra. In addition, the NP/PFD complexes spread into the urethral epithelium 2 weeks after surgery. Ultimately, urethral strictures were significantly reduced with the placement of the NP/PFD complex catheter. Conclusion: Our catheter loaded with NP/PFD complexes effectively delivered PFD to the urethral epithelium through continuous local delivery, thereby reducing fibrosis and stricture after urethral injury, which may be associated with the inhibition of TGF-ß1 expression.

Identification of lysosomal genes associated with prognosis in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, representing 40% of all cases of this tumor. Despite immense improvements in understanding the molecular basis, diagnosis, and treatment of LUAD, its recurrence rate is still high. Methods: RNA-seq data from The Cancer Genome Atlas (TCGA) LUAD cohort were download from Genomic Data Commons Portal. The GSE13213 dataset from Gene Expression Omnibus (GEO) was used for external validation. Differential prognostic lysosome-related genes (LRGs) were identified by overlapping survival-related genes obtained via univariate Cox regression analysis with differentially expressed genes (DEGs). The prognostic model was built using Kaplan-Meier curves and least absolute shrinkage and selection operator (LASSO) analyses. In addition, univariate and multivariate Cox analyses were employed to identify independent prognostic factors. The responses of patients to immune checkpoint inhibitors (ICIs) were further predicted. The pRRophetic package and rank-sum test were used to compute the half maximal inhibitory concentrations (IC50) of 56 chemotherapeutic drugs and their differential effects in the low- and high-risk groups. Moreover, quantitative real-time polymerase chain reaction, Western blot, and human protein atlas (HPA) database were used to verify the expression of the four prognostic biomarkers in LUAD. Results: Of the nine candidate differential prognostic LRGs, GATA2, TFAP2A, LMBRD1, and KRT8 were selected as prognostic biomarkers. The prediction of the risk model was validated to be reliable. Cox independent prognostic analysis revealed that risk score and stage were independent prognostic factors in LUAD. Furthermore, the nomogram and calibration curves of the independent prognostic factors performed well. Differential analysis of ICIs revealed CD276, ICOS, PDCD1LG2, CD27, TNFRSF18, TNFSF9, ENTPD1, and NT5E to be expressed differently in the low- and high-risk groups. The IC50 values of 12 chemotherapeutic drugs, including epothilone.B, JNK.inhibitor.VIII, and AKT.inhibitor.VIII, significantly differed between the two risk groups. KRT8 and TFAP2A were highly expressed, while GATA2 and LMBRD1 were poorly expressed in LUAD cell lines. In addition, KRT8 and TFAP2A were highly expressed, while GATA2 and LMBRD1 were poorly expressed in tumor tissues. Conclusions: Four key prognostic biomarkers-GATA2, TFAP2A, LMBRD1, and KRT8-were used to construct a significant prognostic model for LUAD patients.

Cuproptosis in lung cancer: mechanisms and therapeutic potential.

Cuproptosis, a recently identified form of cell death that differs from other forms, is induced by the disruption of the binding of copper to mitochondrial respiratory acylation components. Inducing cell cuproptosis and targeting cell copper death pathways are considered potential directions for treating tumor diseases. We have provided a detailed introduction to the metabolic process of copper. In addition, this study attempts to clarify and summarize the relationships between cuproptosis and therapeutic targets and signaling pathways of lung cancer. This review aims to summarize the theoretical achievements for translating the results of lung cancer and cuproptosis experiments into clinical treatment.

Identification of a polycomb group-related gene signature for predicting prognosis and immunotherapy efficacy in lung adenocarcinoma.

Background: Several studies have reported the role of polycomb group (PcG) genes in human cancers; however, their role in lung adenocarcinoma (LUAD) is unknown. Methods: Firstly, consensus clustering analysis was used to identify PcG patterns among the 633 LUAD samples in the training dataset. The PcG patterns were then compared in terms of the overall survival (OS), signaling pathway activation, and immune cell infiltration. The PcG-related gene score (PcGScore) was developed using Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to estimate the prognostic value and treatment sensitivity of LUAD. Finally, the prognostic ability of the model was validated using a validation dataset. Results: Two PcG patterns were obtained by consensus clustering analysis, and the two patterns showed significant differences in prognosis, immune cell infiltration, and signaling pathways. Both the univariate and multivariate Cox regression analyses confirmed that the PcGScore was a reliable and independent predictor of LUAD (P<0.001). The high- and low-PCGScore groups showed significant differences in the prognosis, clinical outcomes, genetic variation, immune cell infiltration, and immunotherapeutic and chemotherapeutic effects. Lastly, the PcGScore demonstrated exceptional accuracy in predicting the OS of the LUAD patients in a validation dataset (P<0.001). Conclusions: The study indicated that the PcGScore could serve as a novel biomarker to predict prognosis, clinical outcomes, and treatment sensitivity for LUAD patients.

ADCY9 functions as a novel cancer suppressor gene in lung adenocarcinoma.

Background: The process of lucubrating into lung adenocarcinoma (LUAD) is of profound clinical and practical significance in improving the prognosis of LUAD patients. Multiple biomarkers are reportedly involved in the proliferation or metastasis of adenocarcinoma. However, whether the ADCY9 gene influences the development of LUAD remains unknown. Therefore, we aimed to elucidate the relationship between the expression of ADCY9 and the proliferation and migration of LUAD. Methods: The ADCY9 gene was filtered via a survival analysis of LUAD acquired from the Gene Expression Omnibus (GEO). Then, we conducted a validation analysis and ADCY9-microRNA, microRNA-lncRNA, and ADCY9-lncRNA targeting relationship analysis through the data obtained from The Cancer Genome Atlas (TCGA) dataset. The survival curve, correlation, and prognostic analysis were implemented through bioinformatics methods. Both protein and mRNA expression levels of LUAD cell lines and LUAD patient samples (80 pairs) were detected using western blot assays and quantitative real-time polymerase chain reaction (qRT-PCR). An immunohistochemistry assay was performed to display the correlation between the expression level of the ADCY9 gene and prognosis in LUAD patients (2012-2013; n=115). Overexpression of cell lines SPCA1 and A549 were used for a series of cell function assays. Results: Compared with the expression level in adjacent normal tissues, ADCY9 expression was downregulated in LUAD tissues. Based on the result of the survival curve analysis, high expression of ADCY9 may lead to a better prognosis and may be seen as an independent predictor for LUAD patients. High expression of ADCY9-related microRNA hsa-miR-7-5p may lead to a worse prognosis, and high expression of hsa-miR-7-5p-related lncRNAs may lead to the opposite effects. Overexpression of ADCY9 restrained the proliferation, invasion, and migration abilities of SPCA1, A549 cells. Conclusions: Results indicate that the ADCY9 gene acts as a tumor suppressor to restrain the proliferation, migration, and invasion in LUAD and can lead to a better survival or prognosis in LUAD patients.

Shedding light on macrophage immunotherapy in lung cancer.

The search for therapeutic options for lung cancer continues to advance, with rapid advances in the search for therapies to improve patient prognosis. At present, systemic chemotherapy, immune checkpoint inhibitor therapy, antiangiogenic therapy, and targeted therapy for driver gene positivity are available in the clinic. Common clinical treatments fail to achieve desired outcomes due to immunosuppression of the tumor microenvironment (TME). Tumor immune evasion is mediated by cytokines, chemokines, immune cells, and other cells such as vascular endothelial cells within the tumor immune microenvironment. Tumor-associated macrophages (TAMs) are important immune cells in the TME, inducing tumor angiogenesis, encouraging tumor cell proliferation and migration, and suppressing antitumor immune responses. Thus, TAM targeting becomes the key to lung cancer immunotherapy. This review focuses on macrophage phenotype, polarization mechanism, role in lung cancer, and advances in macrophage centric immunotherapies.

Cancellous bone should not be exposed during medialized rotator cuff repair based on bone-to-tendon healing in a rat mode.

PURPOSE: To compare the biological bone-to-tendon healing using three different medialized bone bed preparation techniques (i.e. cortical bone exposure, cancellous bone exposure, and no cartilage removal) in a rat model of medialized rotator cuff repair. METHODS: Twenty-one male Sprague-Dawley rats with 42 shoulders were subjected to bilateral supraspinatus tenotomy from the greater tuberosity. The rotator cuff was repaired using medialized anchoring with the cortical bone exposed, the cancellous bone exposed, or no cartilage removed. Four and three rats in each group were killed for biomechanical testing and histological evaluation, respectively, at postoperative 6 weeks. RESULTS: All rats survived until the end of the study, but one infected shoulder in the cancellous bone exposure group was excluded from further analysis. Compared with the cortical bone exposure and no cartilage removal groups, the rotator cuff healing of the cancellous bone exposure group showed significantly lower maximum load (cancellous bone exposure group: 26.2 ± 2.3 N, cortical bone exposure group: 37.6 ± 7.9 N, no cartilage removal group: 34.6 ± 7.2 N, P = 0.005 and 0.029) and less stiffness (cancellous bone exposure group: 10.5 ± 2.4 N/mm, cortical bone exposure group: 17.4 ± 6.7 N, no cartilage removal group: 16.0 ± 3.9 N, P = 0.015 and 0.050) at postoperative 6 weeks. In all three groups, the repaired supraspinatus tendon healed towards the original insertion rather than the medialized insertion. The cancellous bone exposure group showed inferior fibrocartilage formation and insertion healing. CONCLUSIONS: The medialized bone-to-tendon repair strategy does not guarantee complete histological healing, and the removal of excessive bony structure impairs bone-to-tendon healing. This study concludes that surgeons should not expose the cancellous bone during the medialized rotator cuff repair.

Sustainably released nanoparticle-based rhynchophylline limits pulmonary fibrosis by inhibiting the TEK-PI3K/AKT signaling pathway.

Background: Pulmonary fibrosis (PF) is a rapidly progressing and irreversible disease, and the currently available types of clinical drugs are limited and inefficient. In our previous study, we observed that Rhynchophylline (Rhy) hindered tendon adhesion and stimulated the healing of injured tendon structures. Considering the similar mechanisms between adhesion formation and PF, we explored the roles of Rhy in PF. Methods: The cytotoxicity of Rhy was tested by a Cell Counting Kit-8 (CCK-8) assay. The degree of PF was evaluated by Western blot (WB), Masson and hematoxylin-eosin (HE) staining, and hydroxyproline quantification. The Rhy-loaded nanoparticles were prepared through an emulsification sonication technique and characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The release of the Rhy-loaded nanoparticles was tested using the absorbance value of the supernatant. Transcriptome sequencing was performed to determine the downstream target and pathway of Rhy, which was then verified by WB. Results: In vitro, Rhy decreased Transforming Growth Factor Beta 1 (TGF-ß1)-induced abnormal overexpression of fibronectin (FN), collagen I (Col I), α-smooth muscle actin (α-SMA) in a dose-dependent manner in human lung fibroblast (HFL1) cells. In vivo, we confirmed (through Masson staining) that the intraperitoneal injection of Rhy reduced collagen deposition and the fibrotic area in a dose-dependent manner. Our results indicated that the Rhy-loaded nanoparticles intratracheal spray intuitively narrowed collagen deposition, shrank collagen deposition and the fibrotic area (Masson and HE staining), and reduced the expression of fibrosis-related markers (WB). Meanwhile, the lung index value and hydroxyproline content were markedly lower than the bleomycin (BLM)-treated group. By transcriptional sequencing analysis, we identified Receptor Tyrosine Kinase (TEK)-Phosphatidylinositol 3-Kinase/Protein Kinase B (PI3K/AKT) as the downstream target and pathway of Rhy. It was also observed that Rhy could reverse the TGF-ß1-induced TEK and phosphorylated AKT (p-AKT) elevated expression. Conclusions: Our findings indicate that Rhy constrained PF progression by inhibiting TEK-PI3K/AKT signaling pathway. Hence, this sustainable release system of Rhy is a highly effective therapy to limit PF and should be developed.

A cuproptosis-related lncRNAs risk model to predict prognosis and guide immunotherapy for lung adenocarcinoma.

Background: Cuproptosis, one of the newest forms of cell death induction, is attracting mounting attention. However, the role of cuproptosis in lung cancer is currently unclear. In this study, we constructed a prognostic signature utilizing cuproptosis-related long noncoding RNAs (CRL) in lung adenocarcinoma (LUAD) and researched its clinical and molecular function. Methods: RNA-related and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed CRLs were screened using the 'limma' package of R software. We used coexpression analysis and univariate Cox analysis to further identify prognostic CRLs. Applying least absolute shrinkage and selection operator (LASSO) regression and Cox regression models, a prognostic risk model based on 16 prognostic CRLs was constructed. To validate prognostic CRL function in LUAD, vitro experiments were conducted to explore the expression of GLIS2-AS1, LINC01230, and LINC00592 in LUAD. Subsequently, according to a formula, patients in the training, test, and overall groups were split into high- and low-risk groups. Kaplan-Meier and receiver operating characteristic (ROC) analyses were applied to assess the predictability of the risk model. Finally, the associations between risk signature and immunity-related analysis, somatic mutation, principal component analysis (PCA), enriched molecular pathways, and drug sensitivity was investigated. Results: A cuproptosis-related long noncoding RNAs (lncRNAs) signature was constructed. Using quantitative polymerase chain reaction (qPCR) trial, we verified that the expressions of GLIS2-AS1, LINC01230, and LINC00592 in LUAD cell lines and tissues were consistent with the above screening results. Based on this signature, a total of 471 LUAD samples from TCGA data set were split into two risk groups based on the computed risk score. The risk model showed a better capacity in predicting prognosis than traditional clinicopathological features. Moreover, significant differences were found in immune cell infiltration, drug sensitivity, and immune checkpoint expression between the two risk groups. Conclusions: The CRLs signature was shown to be a prospective biomarker to forecast prognosis in patients with LUAD and presents new insights for personalized treatment of LUAD.

Absorbable suture knots on the supraspinatus tendon prevent adverse effects of nonabsorbable suture knots in a rat model.

PURPOSE: To compare the absorbable and nonabsorbable suture knots on the tendon on bone-to-tendon healing during the early phase in a rat rotator cuff tear (RCT) model. METHODS: Fifty-two male Sprague-Dawley rats (10 weeks old; mean weight, 380 g) were used in this study, and 51 of them were randomly assigned into three groups: absorbable suture group (ASG, n = 22), nonabsorbable suture group (NSG, n = 22), and sham surgery group (SSG, n = 7), and the remaining rat was used to take surgical pictures. Bilateral supraspinatus tendon tears were created and repaired immediately in ASG and NSG. Three rats from ASG and NSG were killed for Western blot and histological evaluation at 3 days, 1 week, and 4 weeks after surgery. At 4 weeks, four rats from each group were killed for biomechanical test, and three rats from SSG were used for histological evaluation. RESULTS: Absorbable suture knots on the tendon completely degraded at 4 weeks. However, nonabsorbable suture knots remained intact between the tendon and articular side. ASG showed a stronger inflammatory reaction at 3 days and 1 week, but a weaker reaction at 4 weeks as confirmed by gross observation and Western blot. Besides, ASG showed superior biomechanical properties in terms of maximum load to failure and stiffness at 4 weeks. Modified Bonar score revealed superior maturity for tissue healing in ASG to that in NSG at 4 weeks. Furthermore, inferior bone-to-tendon interface and weakest link formation were observed in NSG on histologic images. CONCLUSION: Absorbable suture knots on the tendon contributed to better mechanical properties compared with the nonabsorbable one after rotator cuff repair.

Novel immunogenic cell death-related risk signature to predict prognosis and immune microenvironment in lung adenocarcinoma.

PURPOSE: Immunogenic cell death (ICD) is a type of regulated cell death (RCD) which was discovered to activate adaptive immunity. To date, the effect of ICD on lung adenocarcinoma (LUAD) remains unclear. In this research, we will study the role of ICD-related genes (ICDG) in LUAD. METHODS: RNA sequencing and clinical data were gathered from TCGA-LUAD cohorts and GEO database. Using unsupervised cluster analysis, three clusters were identified with distinctive immune characteristics and significant overall survival based on 18 ICDG. Using LASSO Cox regression, three genes were identified and used to construct the prognosis signature. The association between the 3-ICDG risk signature and immune microenvironment analysis, somatic mutation, and enriched molecular pathways was investigated. RESULTS: Consensus clustering separated the LUAD samples into three clusters (ICDcluster A, B and C), and ICDcluster B had the best prognosis. Different TME cell infiltration characteristics and biological behavior were found in three ICD clusters. Prognostic risk model was contrasted based on the 3 best prognostic ICD-related genes. Subsequently, vitro experiments verified the above analysis results. The high-risk group showed a poor prognosis and enrichment of cancer promoting signal pathway. Multivariate analysis indicated that this 3-ICDG prognostic model might be an accurate prediction parameter for LUAD. Moreover, conducting immune related analysis, we found that the 3-ICDG risk signature was characterized by an immune-active subtype on account of the high infiltration of immune-active cells. CONCLUSION: This study expands our cognition of ICD in LUAD microenvironment, excavated prognostic biomarkers, and provided potential value for guiding immunotherapy and chemotherapy.

Analysis of prognostic model based on immunotherapy related genes in lung adenocarcinoma.

Lung cancer is one of the most common malignant tumors, and ranks high in the list of mortality due to cancers. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Despite progress in the diagnosis and treatment of lung cancer, the prognosis of these patients remains dismal. Therefore, it is crucial to identify the predictors and treatment targets of lung cancer to provide appropriate treatments and improve patient prognosis. In this study, the gene modules related to immunotherapy were screened by weighted gene co-expression network analysis (WGCNA). Using unsupervised clustering, patients in The Cancer Genome Atlas (TCGA) were divided into three clusters based on the gene expression. Next, gene clustering was performed on the prognosis-related differential genes, and a six-gene prognosis model (comprising PLK1, HMMR, ANLN, SLC2A1, SFTPB, and CYP4B1) was constructed using least absolute shrinkage and selection operator (LASSO) analysis. Patients with LUAD were divided into two groups: high-risk and low-risk. Significant differences were found in the survival, immune cell infiltration, Tumor mutational burden (TMB), immune checkpoints, and immune microenvironment between the high- and low-risk groups. Finally, the accuracy of the prognostic model was verified in the Gene Expression Omnibus (GEO) dataset in patients with LUAD (GSE30219, GSE31210, GSE50081, GSE72094).

Histone acetylation modification regulator-mediated tumor microenvironment infiltration characteristics and prognostic model of lung adenocarcinoma patients.

Background: The incidence rate of lung adenocarcinoma (LUAD) is rapidly increasing. Recent studies have reported that histone acetylation modification plays an important role in the occurrence and development of tumors. However, the potential role of modification of histone acetylation modification in the development of tumor immune microenvironment is still unclear. Methods: In this study, we comprehensively evaluated the acetylation modification patterns of LUAD samples obtained from various different databases based on 36 histone modification regulators, and constructed a prognostic model based on The Cancer Genome Atlas (TCGA) LUAD cohort using the Cox regression method. The close relationship between histone acetylation and tumor immune characteristics was further studied, including immune infiltration, immune escape and immunotherapy. Finally, we combined three cohort (GSE30219, GSE72094 and GSE50081) from Gene Expression Omnibus (GEO) database to verify the above results. Results: We analyzed the expression, mutation and interaction of 36 histone acetylation regulated genes. After Univariate Cox regression analysis and least absolute shrinkage and selection operator regression (LASSO), 5 genes (KAT2B, SIRT2, HDAC5, KAT8, HDAC2) were screened to establish the prognosis model and calculate the risk score. Then, patients in the TCGA cohort were divided into high- and low-risk groups based on the risk scores. Further analysis indicated that patients in the high-risk group exhibited significantly reduced overall survival (OS) compared with those in the low-risk group. The high- and low-risk groups exhibited significant differences in terms of tumor immune characteristics, such as immune infiltration, immune escape and immunotherapy. The high-risk group had lower immune score, less immune cell infiltration and higher clinical stage. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. In addition, drugs sensitive for this classification were identified. Finally, the efficacy of the prognostic model was validated by cohort (GSE30219, GSE72094 and GSE50081) from GEO database. Conclusions: Our study provided a robust signature for predicting changing prognosis of patients with LUAD. Thus, it appears to be a potentially useful prognostic tool. Moreover, the important relationship between histone acetylation and tumor immune microenvironment was revealed.

Characteristic of Molecular Subtypes in Lung Squamous Cell Carcinoma Based on Autophagy-Related Genes and Tumor Microenvironment Infiltration.

Background: Recently, a large number of studies have sought personalized treatment for lung squamous cell carcinoma (LUSC) by dividing patients into different molecular subtypes. Autophagy plays an important role in maintaining the tumor microenvironment and immune-related biological processes. However, the molecular subtypes mediated by autophagy in LUSC are not clear. Methods: Based on 490 LUSC samples, we systematically analyzed the molecular subtype modification patterns mediated by autophagy-related genes. The ssGSEA and CIBERSORT algorithm were utilized to quantify the relative abundance of TME cell infiltration. Principal component analysis was used to construct autophagy prognostic score (APS) model. Results: We identified three autophagy subtypes in LUSC, and their clinical outcomes and TME cell infiltration had significant heterogeneity. Cluster A was rich in immune cell infiltration. The enrichment of EMT stromal pathways and immune checkpoint molecules were significantly enhanced, which may lead to its immunosuppression. Cluster B was characterized by relative immunosuppression and relative stromal activation. Cluster C was activated in biological processes related to repair. Patients with high APS were significantly positively correlated with TME stromal activity and poor survival. Meanwhile, high APS showed an advantage in response to anti-PD1 and anti-CTLA4 immunotherapy. Conclusion: This study explored the autophagy molecular subtypes in LUSC. We also discovered the heterogeneity of TME cell infiltration driven by autophagy-related genes. The established APS model is of great significance for evaluating the prognosis of LUSC patients, the infiltration of TME cells, and the effect of immunotherapy.

Chloride Intracellular Channel 1 is a Potential Biomarker for Breast Cancer.

Purpose: Multiple reports have demonstrated that highly expressed chloride intracellular channel 1 (CLIC1) exists in a range of malignant tumors and is involved in proliferation, invasion, and migration of cancer cells. There are few studies on CLIC1 and breast cancer (BC). The purpose of this research was to evaluate the expression level of CLIC1 in BC and its impact on prognosis of BC patients. Patients and Methods: Differences in CLIC1 expression levels in 25 pairs of BC and corresponding paracancerous specimens were tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemistry (IHC) was performed to discuss the relevance between CLIC1 expression in BC tissue chips and clinicopathological parameters of BC patients. The effect of CLIC1 expression on patient prognosis was evaluated by Kaplan-Meier survival curve and Cox regression analysis. Receiver operating characteristic (ROC) curve assessed the diagnostic performance of CLIC1 for BC. Results: The experimental results of qRT-PCR and WB demonstrated that CLIC1 was highly expressed in BC tissues. IHC results showed that overexpression of CLIC1 was strictly correlated with tumor size, TNM classification, pathological grade, lymph node metastasis and Ki67. Patients with lower CLIC1 expression had longer overall survival (OS) and progression-free survival (PFS). Cox regression analysis and ROC curve confirmed that CLIC1 could independently influence the prognosis of BC patients and might have diagnostic efficiency. Conclusion: Overexpressed CLIC1 is closely related to the progression of BC and the poor prognosis of the patients, suggesting that it may act as a potential biological diagnostic index for BC.

PRKCB is relevant to prognosis of lung adenocarcinoma through methylation and immune infiltration.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the tumor-related diseases with high morbidity worldwide. Epigenetic modifications such as DNA methylation changes may involve in tumorigenesis. This study aimed to explore new biomarkers that have prognostic significance of LUAD. METHODS: First, we downloaded the gene expression and methylation data set from Gene Expression Omnibus. R software was then used to identify abnormally methylated differentially expressed genes (MDEGs). Next, R package Cluster Profiler was used to analyze the enrichment and pathway of the MDEGs. Analysis using STRING revealed the protein-protein interaction network. The result was then visualized by Cytoscape and obtained 10 hub genes. Afterward, they were further verified by The Cancer Genome Atlas to select candidate genes. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to verify the expression and prognostic value of candidate genes in LUAD patients. RESULTS: The results showed that the expressions of ADCY5 and PRKCB are indeed related to LUAD. The clinical relevance to PRKCB was confirmed by its clinical correlation analysis. Gene set enrichment analysis (GSEA) and tumor immune estimation resource (TIMER) tumor immune correlations showed that PRKCB is involved in the cancer-related Kyoto Encyclopedia of Genes and Genomes pathway and is involved in immune infiltration. It was also verified by qRT-PCR and immunohistochemistry that PRKCB was lowly expressed in LUAD patients and correlated with prognosis. CONCLUSIONS: PRKCB is relevant to prognosis of LUAD through methylation and immune infiltration.

Characteristic of molecular subtypes in lung adenocarcinoma based on m6A RNA methylation modification and immune microenvironment.

BACKGROUND: Lung adenocarcinoma (LUAD) is a major subtype of lung cancer and closely associated with poor prognosis. N6-methyladenosine (m6A), one of the most predominant modifications in mRNAs, is found to participate in tumorigenesis. However, the potential function of m6A RNA methylation in the tumor immune microenvironment is still murky. METHODS: The gene expression profile cohort and its corresponding clinical data of LUAD patients were downloaded from TCGA database and GEO database. Based on the expression of 21 m6A regulators, we identified two distinct subgroups by consensus clustering. The single-sample gene-set enrichment analysis (ssGSEA) algorithm was conducted to quantify the relative abundance of the fraction of 28 immune cell types. The prognostic model was constructed by Lasso Cox regression. Survival analysis and receiver operating characteristic (ROC) curves were used to evaluate the prognostic model. RESULT: Consensus classification separated the patients into two clusters (clusters 1 and 2). Those patients in cluster 1 showed a better prognosis and were related to higher immune scores and more immune cell infiltration. Subsequently, 457 differentially expressed genes (DEGs) between the two clusters were identified, and then a seven-gene prognostic model was constricted. The survival analysis showed poor prognosis in patients with high-risk score. The ROC curve confirmed the predictive accuracy of this prognostic risk signature. Besides, further analysis indicated that there were significant differences between the high-risk and low-risk groups in stages, status, clustering subtypes, and immunoscore. Low-risk group was related to higher immune score, more immune cell infiltration, and lower clinical stages. Moreover, multivariate analysis revealed that this prognostic model might be a powerful prognostic predictor for LUAD. Ultimately, the efficacy of this prognostic model was successfully validated in several external cohorts (GSE30219, GSE50081 and GSE72094). CONCLUSION: Our study provides a robust signature for predicting patients' prognosis, which might be helpful for therapeutic strategies discovery of LUAD.

Extrachromosomal circular DNA: a new potential role in cancer progression.

Extrachromosomal circular DNA (eccDNA) is considered a circular DNA molecule that exists widely in nature and is independent of conventional chromosomes. eccDNA can be divided into small polydispersed circular DNA (spcDNA), telomeric circles (t-circles), microDNA, and extrachromosomal DNA (ecDNA) according to its size and sequence. Multiple studies have shown that eccDNA is the product of genomic instability, has rich and important biological functions, and is involved in the occurrence of many diseases, including cancer. In this review, we focus on the discovery history, formation process, characteristics, and physiological functions of eccDNAs; the potential functions of various eccDNAs in human cancer; and the research methods employed to study eccDNA.