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BACKGROUND: The prognosis and survival of lung adenocarcinoma (LUAD) patients are still not promising despite recent breakthroughs in treatment. Endoplasmic reticulum stress (ERS) is a self-protective mechanism resulting from an imbalance in quality control of unfolded proteins when cells are stressed, which plays an active role in lung cancer development, but the relationship between ERS and the pathological characteristics and clinical prognosis of LUAD patients remains unclear. METHODS: LASSO and Cox regression were applied based on sequencing information to construct the model, which was validated to be robust. The risk scores of the patients were calculated using the formula provided by the model, and the patients were divided into high and low-risk groups according to the median cut-off of risk scores. Cox regression analysis identifies independent prognostic factors for these patients, and enrichment analysis of prognosis-related genes was also performed. The relationship between risk scores and tumor mutation burden (TMB), cancer stem cell index, and drug sensitivity was explored. RESULTS: We constructed a 13-gene prognostic model for LUAD patients. Patients in the high-risk group had worse overall survival, lower immune score and ESTIMATE score, higher TMB, higher cancer stem cell index, and higher sensitivity to conventional chemotherapeutic agents. In addition, we constructed a nomogram that predicts 5-year survival in LUAD patients, which helps clinicians to foresee the prognosis from a new perspective. CONCLUSIONS: Our results highlight the association of ERS with LUAD and the potential use of ERS in guiding treatment.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Factores de Riesgo , Estrés del Retículo Endoplásmico/genética , Células Madre NeoplásicasRESUMEN
Perioperative myocardial injury is a common complication caused by major surgery. Many pharmacological and nonpharmacological studies have investigated perioperative cardioprotection. However, the methods are insufficient to meet the increasing clinical needs for cardioprotection. The application of Mesenchymal Stem Cell-Derived Exosomes (MSC-Exos) is a novel cell-free therapeutic strategy and has significantly benefitted patients suffering from various diseases. In this review, we comprehensively analyzed the application of MSC-Exos to prevent myocardial infarction/injury by regulating inflammatory reactions, inhibiting cardiomyocyte apoptosis and autophagy, promoting angiogenesis, and mediating cardiac remodeling. Finally, we assessed the therapeutic effects and the challenges associated with the application of MSC-Exos from a clinical perspective.
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Background: Exosomes are involved in tumorigenesis, growth and metastasis. However, the prognostic value of exosome-related genes in lung adenocarcinoma (LUAD) remains unclear. Methods: Clinical and transcriptome data from The Cancer Genome Atlas LUAD cohort were used to construct a model based on exosome-related genes, which was validated with LUAD data from the Gene Expression Omnibus (GEO). Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were used to explore underlying mechanisms; the single-sample gene set enrichment analysis score was used to determine immune functions. Results: A 19-exosome-related gene signature for overall survival in LUAD was predictive in both The Cancer Genome Atlas and GEO LUAD cohorts. Immune-related and extracellular matrix-related pathways were enriched in differentially expressed genes. Immune states differed between high- and low-risk groups. Conclusion: The novel signature can be used to predict outcomes in LUAD.
Lay abstract Exosome products are related to tumorigenesis, growth and metastasis, and also have potential prognostic value in lung cancer. The data and information for lung adenocarcinoma patients retrieved from databases were used to develop a risk score model. The molecular mechanisms and immune system activity in high- and low-risk groups of patients with lung adenocarcinoma based on the median risk score were obviously different. The risk score model contained 19 related genes. Patients with low-risk scores had better prognoses. The novel risk score model can be used to predict the outcome for patients with lung adenocarcinoma.
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Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/genética , Exosomas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/mortalidad , Adenocarcinoma del Pulmón/genética , Adulto , Anciano , Anciano de 80 o más Años , Conjuntos de Datos como Asunto , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Pronóstico , RNA-Seq , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , TranscriptomaRESUMEN
Aims: To elucidate the association between ferroptosis-related genes and prognosis in patients with lung adenocarcinoma (LUAD). Materials & methods: A ferroptosis-related gene signature was made by lasso regression analysis through the LUAD datasets of the Cancer Genome Atlas. The prognostic value of the multigene signature was externally validated in the GSE72094 dataset from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were used to explore underlying mechanisms. Results & conclusion: We established a novel ferroptosis-related gene signature for overall survival in LUAD that was predictive in both the training and validation cohorts. Immune-related pathways were significantly enriched, and immune status differed between the high- and low-risk groups. Targeting ferroptosis is a potential therapeutic option in LUAD. These results still need to be confirmed by more studies.
Lay abstract Lung adenocarcinoma (LUAD) is a common type of lung cancer, a major contributor to cancer-related death in men and women worldwide. Ferroptosis is a form of regulated cell death that is dependent on iron. The relationship between ferroptosis-related gene expression and survival in patients with LUAD remains to be elucidated. In this article, the public datasets the Cancer Genome Atlas and the Gene Expression Omnibus were used to create a model with 12 ferroptosis genes to separate LUAD patients into high- and low-risk groups. The low-risk group had better survival than the high-risk group. We also found that the immune status was different in high-risk and low-risk patients. In conclusion, our study established a novel ferroptosis-related gene signature for survival in LUAD. The underlying mechanisms involve tumor immunity.
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Adenocarcinoma del Pulmón/mortalidad , Biomarcadores de Tumor/genética , Ferroptosis/genética , Neoplasias Pulmonares/mortalidad , Transcriptoma/genética , Adenocarcinoma del Pulmón/genética , Adulto , Anciano , Anciano de 80 o más Años , Conjuntos de Datos como Asunto , Femenino , Perfilación de la Expresión Génica/estadística & datos numéricos , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricosRESUMEN
OBJECTIVE: To identify the predictive factors associated with pleural drainage volume (PDV) after uniportal video-assisted thoracic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC). METHODS: A total of 440 consecutive NSCLC patients who underwent uniportal VATS lobectomy were enrolled in this study between November 2016 and July 2019. Thirty-four parameters, including patients' clinicopathological characteristics and other potential predictors were collected. Daily drainage volume was summed up as PDV. Univariate analysis and multivariate regression models were fitted to identify independent predictive factors for PDV. RESULTS: The median PDV was 840 ml during the median drainage duration of 4 days. A strong correlation was observed between PDV and drainage duration (correlation coefficient = 0.936). On univariate analysis, age, forced expiratory volume in 1 s % predicted (FEV1%), left ventricular ejection fraction (LVEF), operation time, serum total protein (TP), and body mass index (BMI) showed a significant correlation with PDV (P value, < 0.001, < 0.001, 0.003, 0.008, 0.028, and 0.045, respectively). Patients with smoking history (P = 0.030) or who underwent lower lobectomy (P = 0.015) showed significantly increased PDV than never smokers or those who underwent upper or middle lobectomy, respectively. On multivariate regression analysis, older age (P< 0.001), lower FEV1% (P< 0.001), lower LVEF (P = 0.011), lower TP (P = 0.013), and lower lobectomy (P = 0.016) were independent predictors of increased PDV. CONCLUSIONS: Predictive factors of PDV can be identified. Based on these predictors, patients can be treated with tailored individualized safe chest tube management.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anciano , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Drenaje , Humanos , Neoplasias Pulmonares/cirugía , Neumonectomía , Complicaciones Posoperatorias/epidemiología , Pronóstico , Estudios Retrospectivos , Volumen Sistólico , Cirugía Torácica Asistida por Video , Función Ventricular IzquierdaRESUMEN
Magnetic reconnection, the rearrangement of magnetic field topologies, is a fundamental plasma process throughout the universe, which converts magnetic energy to plasma kinetic energy and results in particle energization. A current sheet is a prerequisite for the occurrence of magnetic reconnection. It has been well documented that reconnecting current sheets are prevalent in turbulent plasmas. However, how these current sheets are formed remains unclear. Among natural plasmas, the region downstream of the Earth's bow shock, the magnetosheath, is one of the most turbulent. Here, we show that the reconnecting current sheets in the turbulent magnetosheath originate from the waves in the region upstream of the shock. Once excited, the upstream waves are transmitted across the shock, compressed, and then transformed into current sheets in the downstream region. Magnetic reconnection subsequently occurs in these downstream current sheets. This process can be generalized to various shocked plasmas in astrophysical and laboratorial environments where turbulent magnetic reconnection should be common.
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Lung adenocarcinoma (LUAD) has a poor prognosis. Circadian genes such as TIMELESS have been associated with several pathologies, including cancer. The expression of TIMELESS and the relationship between TIMELESS, infiltration of tumors and prognosis in LUAD requires further investigation. In this study, we investigated the expression of TIMELESS and its association with survival across several types of human cancer using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Program. Noncoding RNAs (ncRNAs) regulating overexpression of TIMELESS in lung adenocarcinoma (LUAD) were explored with expression, correlation, and survival analyses. Immune cell infiltration and biomarkers were analyzed between different TIMELESS expression levels. The relationship between TIMELESS expression and immunophenoscores, which were used to predict response to immunotherapy, was evaluated. TIMELESS was identified as a potential oncogene in LUAD. NcRNA analysis showed MIR4435-2HG/hsa-miR-1-3p may interact with TIMELESS in a competitive endogenous RNA network in LUAD tumor tissues. Most immune cells were significantly decreased in TCGA LUAD tumor tissues with high TIMELESS expression except for CD4+T cells and Th2 cells. TIMELESS expression in LUAD tumor tissues was significantly negatively correlated with neutrophil biomarkers, dendritic cell biomarkers (HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DPA1, CD1C) and an immunophenoscore that predicted outcomes associated with the use of immune checkpoint inhibitors. These findings imply that ncRNAs-mediated TIMELESS overexpression in LUAD tumor tissues correlated with poor prognosis, reduced immune cell infiltration in the tumor microenvironment, and poor response to immune checkpoint inhibitors.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Biomarcadores , Inhibidores de Puntos de Control Inmunológico , Oncogenes , ARN no Traducido , Microambiente TumoralRESUMEN
Lung cancer, acknowledged as one of the most fatal cancers globally, faces limited treatment options on an international scale. The success of clinical treatment is impeded by challenges such as late diagnosis, restricted treatment alternatives, relapse, and the emergence of drug resistance. This predicament has led to a saturation point in lung cancer treatment, prompting a rapid shift in focus towards the tumor microenvironment (TME) as a pivotal area in cancer research. Within the TME, Interleukin-1 (IL-1) is abundantly present, originating from immune cells, tissue stromal cells, and tumor cells. IL-1's induction of pro-inflammatory mediators and chemokines establishes an inflammatory milieu influencing tumor occurrence, development, and the interaction between tumors and the host immune system. Notably, IL-1 expression in the TME exhibits characteristics such as staging, tissue specificity, and functional pluripotency. This comprehensive review aims to delve into the impact of IL-1 on lung cancer, encompassing aspects of occurrence, invasion, metastasis, immunosuppression, and immune surveillance. The ultimate goal is to propose a novel treatment approach, considering the intricate dynamics of IL-1 within the TME.
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Neoplasias Pulmonares , Neoplasias , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Interleucina-1 , Recurrencia Local de Neoplasia , Neoplasias/tratamiento farmacológico , Terapia de Inmunosupresión , Quimiocinas/metabolismo , Microambiente Tumoral , InmunoterapiaRESUMEN
In this study, we explored how ammonium and metal ion stresses affected the production of recombinant hyperthermostable manganese superoxide dismutase (Mn-SOD). To improve Mn-SOD production, fed-batch culture in shake flasks and bioreactor fermentation were undertaken to examine the effects of [Formula: see text] and Mn(2+) feeding. Under the optimized feeding time and concentrations of [Formula: see text] and Mn(2+), the maximal SOD activity obtained from bioreactor fermentation reached some 480 U/ml, over 4 times higher than that in batch cultivation (113 U/ml), indicating a major enhancement of the concentration of Mn-SOD in the scale-up of hyperthermostable Mn-SOD production. In contrast, when the fed-batch culture with appropriate [Formula: see text] and Mn(2+) feeding was carried out in the same 5-L stirred tank bioreactor, a maximal SOD concentration of some 450 U/ml was obtained, again indicating substantial increase in SOD activity as a result of [Formula: see text] and Mn(2+) feeding. The isoelectric point (pI) of the sample was found to be 6.2. It was highly stable at 90 °C and circular dichroism measurements indicated a high α-helical content of 70 % as well, consistent with known SOD properties. This study indicates that [Formula: see text] and Mn(2+) play important roles in Mn-SOD expression. Stress fermentation strategies established in this study are useful for large-scale efficient production of hyperthermostable Mn-SOD and may also be valuable for the scale-up of other extremozymes.
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Amoníaco/farmacología , Proteínas Bacterianas/metabolismo , Fermentación , Manganeso/farmacología , Superóxido Dismutasa/metabolismo , Thermus thermophilus/metabolismo , Proteínas Bacterianas/genética , Técnicas de Cultivo Celular por Lotes/instrumentación , Técnicas de Cultivo Celular por Lotes/métodos , Reactores Biológicos , Estrés Fisiológico , Superóxido Dismutasa/genética , Thermus thermophilus/efectos de los fármacos , Thermus thermophilus/enzimología , Thermus thermophilus/crecimiento & desarrolloRESUMEN
As breast cancer is a multistage progression disease resulting from a genetic sequence of mutations, understanding the genes whose expression values increase or decrease monotonically across pathologic stages can provide insightful clues about how breast cancer initiates and advances. Utilizing variational autoencoder (VAE) networks in conjunction with traditional statistical testing, we successfully ascertain long non-coding RNAs (lncRNAs) that exhibit monotonically differential expression values in breast cancer. Subsequently, we validate that the identified lncRNAs really present monotonically changed patterns. The proposed procedure identified 248 monotonically decreasing expressed and 115 increasing expressed lncRNAs. They correspond to a total of 65 and 33 genes respectively, which possess unique known gene symbols. Some of them are associated with breast cancer, as suggested by previous studies. Furthermore, enriched pathways by the target mRNAs of these identified lncRNAs include the Wnt signaling pathway, human papillomavirus (HPV) infection, and Rap 1 signaling pathway, which have been shown to play crucial roles in the initiation and development of breast cancer. Additionally, we trained a VAE model using the entire dataset. To assess the effectiveness of the identified lncRNAs, a microarray dataset was employed as the test set. The results obtained from this evaluation were deemed satisfactory. In conclusion, further experimental validation of these lncRNAs with a large-sized study is warranted, and the proposed procedure is highly recommended.
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Neoplasias de la Mama , ARN Largo no Codificante , Humanos , Femenino , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias de la Mama/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Vía de Señalización Wnt , ARN Mensajero/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Lung cancer, a major contributor to cancer-related fatalities worldwide, involves a complex pathogenesis. Cathepsins, lysosomal cysteine proteases, play roles in various physiological and pathological processes, including tumorigenesis. Observational studies have suggested an association between cathepsins and lung cancer. However, the causal link between the cathepsin family and lung cancer remains undetermined. This study employed Mendelian randomization analyses to investigate this causal association. The univariable Mendelian randomization analysis results indicate that elevated cathepsin H levels increase the overall risk of lung cancer, adenocarcinoma, and lung cancer among smokers. Conversely, reverse Mendelian randomization analyses suggest that squamous carcinoma may lead to increased cathepsin B levels. A multivariable analysis using nine cathepsins as covariates reveals that elevated cathepsin H levels lead to an increased overall risk of lung cancer, adenocarcinoma, and lung cancer in smokers. In conclusion, cathepsin H may serve as a marker for lung cancer, potentially inspiring directions in lung cancer diagnosis and treatment.
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Adenocarcinoma , Neoplasias Pulmonares , Humanos , Catepsina H , Neoplasias Pulmonares/genética , Análisis de la Aleatorización Mendeliana , Catepsina LRESUMEN
Introduction: According to the principle, thymomas combined with myasthenia gravis (MG) require surgical treatment. However, patients with non-MG thymoma rarely develop MG and early- or late-onset MG after surgery is called postoperative MG (PMG). Our study used a meta-analysis to examine the incidence of PMG and risk factors. Methods: Relevant studies were searched for in the PubMed, EMBASE, Web of Science, CNKI,and Wanfang databases. Investigations that directly or indirectly analyzed the risk factors for PMG development in patients with non-MG thymoma were included in this study. Furthermore, risk ratios (RR) with 95% confidence intervals (CI) were pooled using meta-analysis, and fixed-effects or random-effects models were used depending on the heterogeneity of the included studies. Results: Thirteen cohorts containing 2,448 patients that met the inclusion criteria were included. Metaanalysis revealed that the incidence of PMG in preoperative patients with non-MG thymoma was 8%. Preoperative seropositive acetylcholine receptor antibody (AChR-Ab) (RR = 5.53, 95% CI 2.36 - 12.96, P<0.001), open thymectomy (RR =1.84, 95% CI 1.39 - 2.43, P<0.001), non-R0 resection (RR = 1.87, 95% CI 1.36 - 2.54, P<0.001), world health organization (WHO) type B (RR =1.80, 95% CI 1.07 - 3.04, P= 0.028), and postoperative inflammation (RR = 1.63, 95% CI 1.26 - 2.12, P<0.001) were the risk factors for PMG in patients with thymoma. Masaoka stage (P = 0.151) and sex (P = 0.777) were not significantly associated with PMG. Discussion: Patients with thymoma but without MG had a high probability of developing PMG. Although the incidence of PMG was very low, thymectomy could not completely prevent the occurrence of MG. Preoperative seropositive AChR-Ab level, open thymectomy, non-R0 resection, WHO type B, and postoperative inflammation were risk factors for PMG. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022360002.
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BACKGROUND: The clinical application of normothermic ex vivo lung perfusion (EVLP) has increased donor lung utilization for transplantation through functional assessment. To develop it as a platform for donor lung repair, reconditioning and regeneration, the perfusate should be modified to support the lung during extended EVLP. METHODS: Human lung epithelial cells and pulmonary microvascular endothelial cells were cultured, and the effects of Steen solution (commonly used EVLP perfusate) on basic cellular function were tested. Steen solution was modified based on screening tests in cell culture, and further tested with an EVLP cell culture model, on apoptosis, GSH, HSP70, and IL-8 expression. Finally, a modified formula was tested on porcine EVLP. Physiological parameters of lung function, histology of lung tissue, and amino acid concentrations in EVLP perfusate were measured. RESULTS: Steen solution reduced cell confluence, induced apoptosis, and inhibited cell migration, compared to regular cell culture media. Adding L-alanyl-L-glutamine to Steen solution improved cell migration and decreased apoptosis. It also reduced cold preservation and warm perfusion-induced apoptosis, enhanced GSH and HSP70 production, and inhibited IL-8 expression on an EVLP cell culture model. L-alanyl-L-glutamine modified Steen solution supported porcine lungs on EVLP with significantly improved lung function, well-preserved histological structure, and significantly higher levels of multiple amino acids in EVLP perfusate. CONCLUSIONS: Adding L-alanyl-L-glutamine to perfusate may provide additional energy support, antioxidant, and cytoprotective effects to lung tissue. The pipeline developed herein, with cell culture, cell EVLP, and porcine EVLP models, can be used to further optimize perfusates to improve EVLP outcomes.
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Trasplante de Pulmón , Pulmón , Animales , Humanos , Células Endoteliales , Interleucina-8/farmacología , Pulmón/irrigación sanguínea , Pulmón/fisiología , Preservación de Órganos , Perfusión , PorcinosRESUMEN
To investigate the clinical significance of Tensin4 (TNS4) in human cancers, particularly lung cancer, we mined the Cancer Genome Atlas database for lung adenocarcinoma (TCGA-LUAD) and the Gene Expression Omnibus database to predict poor prognosis based on the up-regulated expression of TNS4 in LUAD. The correlation between the clinical pathologic features of patients and TNS4 gene expression was analyzed using the Wilcoxon signed-rank test. Cox regression analysis was used to evaluate the association of clinicopathologic characteristics with the overall survival (OS) of cancer patients using TCGA data. The relationship between TNS4 expression and cancer patient survival was evaluated with Kaplan-Meier survival curves and meta-analyses. GO and KEGG were also included in the data mining methods. The expression level of TNS4 in LUAD tissue was higher than that in adjacent normal tissue (P < .001). According to the Kaplan-Meier survival curve, LUAD patients with high TNS4 expression had worse prognosis than those with low TNS4 expression (P < .001 for OS; P = .028 for progression-free survival). A positive correlation between TNS4 expression and poor OS was found with both univariate and multivariate analyses. Increased TNS4 expression in LUAD was closely correlated with a higher disease stage (P = .007), positive lymph nodes (P = .005), and larger tumor size (P = .002). Moreover, meta-analysis including seven independent datasets showed LUAD patients with higher TNS4 had poorer OS (combined hazard ratio = 1.27, 95% confidence interval 1.16-1.39). In the high-TNS4 population, regulation of the actin cytoskeleton, extracellular matrix receptor interactions, and focal adhesion were differentially enriched. Integrin α6ß4 and laminin-5 genes were also associated with TNS4. TNS4 expression may be a potential biomarker for predicting poor survival in LUAD. Moreover, the correlation between TNS4 and integrin α6ß4 may be attributed to the role of TNS4 in LUAD.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Integrina alfa6beta4/genética , Integrina alfa6beta4/metabolismo , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Adenocarcinoma del Pulmón/patología , Neoplasias Pulmonares/patología , Pronóstico , Tensinas/genética , Tensinas/metabolismoRESUMEN
BACKGROUND: Whether the size of thymic epithelial tumors (TETs) has an impact on prognosis has long been a controversial issue. Our study was designed to investigate the value of tumor size in the prognosis (overall survival (OS) and relapse-free survival) of patients with TETs. METHODS: We searched the databases such as PubMed, EMBASE, Web of Science, and clinical trials registration system for articles illustrating the impact of tumor size on survival data in TETs patients. We did a meta-analysis for OS and relapse-free survival. RESULTS: We recruited 9 studies in our meta-analysis. Our study illustrates that TETs patients with small tumor size had better relapse-free survival (hazard ratio = 1.66, 95% confidence interval 1.18-2.35, P = .004) and OS (hazard ratio = 1.93, 95% confidence interval 1.30-2.80, P = .001) in comparison to patients with large tumor size. CONCLUSIONS: In conclusion, the results of our meta-analysis showed that TET size was significantly associated with overall and relapse-free survival of patients, with relatively small tumors tending to have a better prognosis.
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Neoplasias Glandulares y Epiteliales , Neoplasias del Timo , Humanos , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
BACKGROUND: The pretreatment prognostic nutritional index (PNI) is an indicator of nutritional and immune status, and has potential use as a predictor of survival in cancer patients. Several retrospective studies have used the PNI to predict the outcome of lung cancer patients receiving different immune checkpoint inhibitors (ICIs), but the results have been inconsistent. The objective of our study is to assess the relationship of pretreatment PNI with survival outcomes in lung cancer patients who received ICI-based treatments by meta-analysis. METHODS: We searched the EMBASE, PubMed, Cochrane Library, American Society of Clinical Oncology, and European Society of Medical Oncology databases to identify studies that reported overall survival (OS) or progression-free survival (PFS) in eligible patients. Eight studies were eligible based on predefined inclusion and exclusion criteria. Data and pooled indicators were extracted from these studies. Meta-analysis was used to analyze hazard ratios (HRs) and 95% confidence intervals (CIs) for OS and/or PFS and the prognostic value of pretreatment PNI. We completed the registration of the research protocol (Registration number: INPLASY202240087, DOI number: 10.37766/inplasy2022.4.0087). RESULTS: We analyzed data from 8 eligible studies (831 patients). Meta-analysis showed that relative to patients with low pretreatment PNI, those with a high pretreatment PNI had better OS (HR = 2.50, 95% CI = 1.44-4.33, P = .001) and better PFS (HR = 1.94, 95% CI = 1.56-2.42, P < .001). Sensitivity analysis indicated these results were robust. There was also no evidence of publication bias. CONCLUSION: Lung cancer patients receiving ICI-based treatments who had higher pretreatment PNI had better OS and PFS.
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Neoplasias Pulmonares , Evaluación Nutricional , Humanos , Pronóstico , Estudios Retrospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Modelos de Riesgos ProporcionalesRESUMEN
Lung cancer is the most common malignancy and is responsible for the largest cancer-related mortality worldwide. Alzheimer's disease is a degenerative neurological disease that burdens healthcare worldwide. While the two diseases are distinct, several transcriptomic studies have demonstrated they are linked. However, no concordant conclusion on how they are associated has been drawn. Since these studies utilized conventional bioinformatics methods, such as the differentially expressed gene (DEG) analysis, it is naturally expected that the proportion of DEGs having either the same or inverse directions in lung cancer and Alzheimer's disease is substantial. This raises the inconsistency. Therefore, a novel bioinformatics method capable of determining the direction of association is desirable. In this study, the moderated t-tests were first used to identify DEGs that are shared by the two diseases. For the shared DEGs, separate autoencoder (AE) networks were trained to extract a one-dimensional representation (pseudogene) for each disease. Based on these pseudogenes, the association direction between lung cancer and Alzheimer's disease was inferred. AE networks based on 266 shared DEGs revealed a comorbidity relationship between Alzheimer's disease and lung cancer. Specifically, Spearman's correlation coefficient between the predicted values using the two AE networks for the Alzheimer's disease test set was 0.825 and for the lung cancer test set was 0.316. Novel bioinformatics methods such as an AE network may help decipher how distinct diseases are associated by providing the refined representations of dysregulated genes.
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Enfermedad de Alzheimer , Neoplasias Pulmonares , Humanos , Enfermedad de Alzheimer/genética , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/genética , Perfilación de la Expresión Génica , Biología Computacional/métodosRESUMEN
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor with many important functions in normal and transformed cells. STAT3 regulatory activities are highly complex as they are involved in various signaling pathways in different cell types under different conditions. Biologically, STAT3 is a regulative factor for normal and cancer stem cells (CSCs). Tumor protein p63 (p63), a member of the p53 protein family, is involved in these biological processes and is also physically and functionally associated with STAT3. STAT3 activation occurs during various aspects of carcinogenesis, including regulation of CSCs properties. In combination with p63, STAT3 is a possible biological marker of CSCs and a major regulator of maintenance of stemness in CSCs. We summarized the STAT3 functions and regulation and its role in CSC properties and highlight how these are affected by its associations with p63.
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Esophageal cancer (EC) is a common tumor of the gastrointestinal system and a major threat to human health. The etiology and incidence of EC vary depending on the type of pathology. Owing to the unique physiological structure of the esophagus and the poor biological behavior of EC, the treatment modalities available are limited, and the prognosis of patients is relatively poor. Curcumin is a type of natural phytochemical belonging to the class of phenolic compounds. It exerts favorable anticancer effects on various cancers. A growing body of evidence indicates that curcumin suppresses tumor development and progression by inhibiting tumor cell proliferation, invasion, and migration, thus inducing apoptosis, regulating microRNA expression, reversing multidrug resistance, and inducing sensitivity to the therapeutic effect of chemoradiotherapy. Multiple cellular molecules, growth factors, and genes encoding proteins participating in different signaling pathways interact with each other to contribute to the complex and orderly anticancer effect. The efficacy and safety of curcumin have been established in preclinical studies for EC and clinical trials for other cancers. However, the low bioavailability of curcumin limits its clinical application. Therefore, the modification of curcumin analogs, the combination of curcumin with other drugs or therapies, and the use of novel nanocarriers have been widely investigated to improve the clinical effects of curcumin in EC.
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BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common subtypes of lung cancer which is the leading cause of death in cancer patients. Circadian clock disruption has been listed as a likely carcinogen. However, whether the expression of circadian genes affects overall survival (OS) in LUAD patients remains unknown. In this article, we identified a circadian gene signature to predict overall survival in LUAD. METHODS: RNA sequencing (HTSeq-FPKM) data and clinical characteristics were obtained for a cohort of LUAD patients from The Cancer Genome Atlas (TCGA). A multigene signature based on differentially expressed circadian clock-related genes was generated for the prediction of OS using Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression analysis, and externally validated using the GSE72094 dataset from the GEO database. RESULTS: Five differentially expressed genes (DEGs) were identified to be significantly associated with OS using univariate Cox proportional regression analysis (P < 0.05). Patients classified as high risk based on these five DEGs had significantly lower OS than those classified as low risk in both the TGCA cohort and GSE72094 dataset (P < 0.001). Multivariate Cox regression analysis revealed that the five-gene-signature based risk score was an independent predictor of OS (hazard ratio > 1, P < 0.001). Receiver operating characteristic (ROC) curves confirmed its prognostic value. Gene set enrichment analysis (GSEA) showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to cell proliferation, gene damage repair, proteasomes, and immune and autoimmune diseases were significantly enriched. CONCLUSION: A novel circadian gene signature for OS in LUAD was found to be predictive in both the derivation and validation cohorts. Targeting circadian genes is a potential therapeutic option in LUAD.