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OBJECTIVES: The long-term prognosis of patients with coronary artery disease (CAD) with diffuse long lesion underwent coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) remains worse. Here, we aimed to identify distinctive genes involved and offer novel insights into the pathogenesis of diffuse long lesion. MATERIALS AND METHODS: Whole exome sequencing was performed on peripheral blood samples from 20 CAD patients with diffuse long lesion (CAD-DLL) and from 10 controls with focal lesion (CAD-FL) through a uniform pipeline. Proteomics analysis was conducted on the serum samples from 10 CAD-DLL patients and from 10 controls with CAD-FL by mass spectrometry. Bioinformatics analysis was performed to elucidate the involved genes, including functional annotation and protein-protein interaction analysis. RESULTS: A total of 742 shared variant genes were found in CAD-DLL patients but not in controls. Of these, 46 genes were identified as high-frequency variant genes (≥ 4/20) distinctive genes. According to the consensus variant site, 148 shared variant sites were found in the CAD-DLL group. The lysosome and cellular senescence-related pathway may be the most significant pathway in diffuse long lesion. Following the DNA-protein combined analysis, eight genes were screened whose expression levels were altered at both DNA and protein levels. Among these genes, the MAN2A2 gene, the only one that was highly expressed at the protein level, was associated with metabolic and immune-inflammatory dysregulation. CONCLUSIONS: Compared to individuals with CAD-FL, patients with CAD-DLL show additional variants. These findings contribute to the understanding of the mechanism of CAD-DLL and provide potential targets for the diagnosis and treatment of CAD-DLL.
Subject(s)
Coronary Artery Disease , Exome Sequencing , Proteomics , Humans , Coronary Artery Disease/genetics , Coronary Artery Disease/surgery , Coronary Artery Disease/blood , Male , Proteomics/methods , Female , Middle Aged , AgedABSTRACT
Observational studies have confirmed that 25-hydroxyvitamin D (25(OH)D) is associated with pulmonary hypertension (PH), but the causal association between each other is unclear. Therefore, Mendelian randomization (MR) method was performed to validate the causal association between PH and serum 25(OH)D levels. The summary data for 25(OH)D and PH were from the National Human Genome Research Institute-European Bioinformatics Institute. Catalog of human genome-wide association studies and FinnGen biobank consortium. MR analysis was utilized to explore the potential causal association between PH and 25(OH)D. To evaluate this association, inverse variance weighting was considered as the primary method. Cochran's Q test, MR-Egger intercept test, and "leave-one-out" sensitivity analyses were utilized to control the pleiotropy and heterogeneity in the study. Two-sample MR analysis revealed an inverse causal relationship between 25(OH)D and PH (odds ratio: 0.376, 95% confidence interval: 0.162-0.876, p = 2.334 × 10-2). There was no significant heterogeneity and pleiotropy. The present study confirmed the inverse causal relationship between 25(OH)D and PH. This pathway may provide another treatment pathway in PH. Further studies to elucidate this pathway is indicated.
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INTRODUCTION: Thymoma is a common mediastinal tumor, but few studies have been performed in thymoma patients 80 years or older. This study aimed to analyze the clinical features, treatment modalities, and survival outcomes of thymoma patients at least 80 years old and compare these features to those of patients younger than 80 years old. METHOD: Data from thymoma patients in the Surveillance, Epidemiology and End Results database between 2000 and 2019 were selected. Clinical features, treatment modalities of the two age groups were compared. Survival rates were calculated by the Kaplan-Meier method and the log-rank test was used to compare survival rates between two groups. Propensity score matching was used based on whether surgery was performed. Univariate and multivariate Cox proportional-hazards regression analyses were performed to identify independent prognostic factors. RESULTS: Compared with the younger patients, the patients aged 80 years or older had a similar distribution of Masaoka-Koga tumor stage, a higher proportion of type A thymoma, and a lower recurrence rate in the early stage. In elderly patients after propensity score matching, the overall survival and cancer-specific survival were better in the surgery group with complete resection and compared with patients of different ages, elderly patients showed similar benefit from surgery as younger patients were observed. CONCLUSION: In thymoma patients aged 80 years or older, surgery still plays an important role in survival outcome. Compared with younger patients, older patients have unique clinical features.
Subject(s)
Thymoma , Thymus Neoplasms , Aged , Humans , Aged, 80 and over , Thymoma/therapy , Thymoma/pathology , Neoplasm Staging , Thymus Neoplasms/therapy , Thymus Neoplasms/pathology , Radiotherapy, Adjuvant , Propensity Score , Prognosis , Retrospective StudiesABSTRACT
Background: The lymph node ratio (LNR) is useful for predicting survival in patients with small cell lung cancer (SCLC). The present study compared the effectiveness of the N stage, number of positive LNs (NPLNs), LNR, and log odds of positive LNs (LODDS) to predict cancer-specific survival (CSS) in patients with SCLC. Materials and methods: 674 patients were screened using the Surveillance Epidemiology and End Results database. The Kaplan-Meier survival and receiver operating characteristic (ROC) curves were performed to address optimal estimation of the N stage, NPLNs, LNR, and LODDS to predict CSS. The optimal LN status group was incorporated into a nomogram to estimate CSS in SCLC patients. The ROC curve, decision curve analysis, and calibration plots were utilized to test the discriminatory ability and accuracy of this nomogram. Results: The LODDS model showed the highest accuracy compared to the N stage, NPLNs, and LNR in predicting CSS for SCLC patients. LODDS, age, sex, tumor size, and radiotherapy status were included in the nomogram. The results of calibration plots provided evidences of nice consistency. The ROC and DCA plots suggested a better discriminatory ability and clinical applicability of this nomogram than the 8th TNM and SEER staging systems. Conclusions: LODDS demonstrated a better predictive power than other LN schemes in SCLC patients after surgery. A novel LODDS-incorporating nomogram was built to predict CSS in SCLC patients after surgery, proving to be more precise than the 8th TNM and SEER staging.
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OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS: The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Subject(s)
Asphyxia Neonatorum , Nomograms , Infant, Newborn , Humans , Male , Pregnancy , Female , Retrospective Studies , Cesarean Section , Risk Factors , Asphyxia Neonatorum/epidemiology , Asphyxia Neonatorum/etiologyABSTRACT
Background: Numerous studies have demonstrated that rheumatoid arthritis (RA) is related to increased incidence of heart failure (HF), but the underlying association remains unclear. In this study, the potential association of RA and HF was clarified using Mendelian randomization analysis. Methods: Genetic tools for RA, HF, autoimmune disease (AD), and NT-proBNP were acquired from genome-wide studies without population overlap. The inverse variance weighting method was employed for MR analysis. Meanwhile, the results were verified in terms of reliability by using a series of analyses and assessments. Results: According to MR analysis, its genetic susceptibility to RA may lead to increased risk of heart failure (OR=1.02226, 95%CI [1.005495-1.039304], P=0.009067), but RA was not associated with NT-proBNP. In addition, RA was a type of AD, and the genetic susceptibility of AD had a close relation to increased risk of heart failure (OR=1.045157, 95%CI [1.010249-1.081272], P=0.010825), while AD was not associated with NT-proBNP. In addition, the MR Steiger test revealed that RA was causal for HF and not the opposite (P = 0.000). Conclusion: The causal role of RA in HF was explored to recognize the underlying mechanisms of RA and facilitate comprehensive HF evaluation and treatment of RA.
Subject(s)
Arthritis, Rheumatoid , Heart Failure , Humans , Genome-Wide Association Study , Genetic Predisposition to Disease , Reproducibility of Results , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/epidemiology , Heart Failure/etiology , Heart Failure/geneticsABSTRACT
Long non-coding RNAs (lncRNAs) play vital roles in regulating epigenetic mechanisms and gene expression levels, and their dysregulation is closely associated with a variety of diseases such as cancer. Several studies have demonstrated that lncRNAs are dysregulated during tumor progression. Recently, the MYC-induced long non-coding RNA MINCR, a newly identified lncRNA, has been demonstrated to act as an oncogene in different cancers, including gallbladder cancer, hepatocellular cancer, colorectal cancer, non-small cell lung cancer, oral squamous cell carcinoma, nasopharyngeal cancer, and glioma. Moreover, MINCR has been reported to act as a biomarker in the prognosis of patients with different cancers. In this review, we summarize and analyze the oncogenic roles of MINCR in a variety of human cancers in terms of its clinical significance, biological functions, cellular activities, and regulatory mechanism. Our analysis of the literature suggests that MINCR has potential as a novel biomarker and therapeutic target in human cancers.
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Background: In recent years, the incidence rates of rheumatoid arthritis (RA) and heart disease (HD) have noticeably increased worldwide. Previous studies have found that patients with RA are more likely to develop HD, while the cause and effect have still remained elusive. In this study, Mendelian randomization (MR) analysis was used to indicate whether there was a potential association between RA and HD. Methods: Data of RA, ischemic heart disease (IHD), myocardial infarction (MI), atrial fibrillation (AF), and arrhythmia were based on the genome-wide association study (GWAS) dataset. No disease group was intersected. Inverse-variance weighted (IVW) method was used to calculate MR estimates, and sensitivity analysis was performed. Results: The primary MR analysis showed that genetic susceptibility to RA was significantly associated with the risk of IHD and MI, rather than with AF and arrhythmia. Besides, there was no heterogeneity and horizontal pleiotropy between the primary and replicated analyses. There was a significant correlation between RA and the risk of IHD (odds ratio (OR), 1.0006; 95% confidence interval (CI), 1.000244-1.00104; P = 0.001552), meanwhile, there was a significant correlation between RA and the risk of MI (OR, 1.0458; 95% CI, 1.07061-1.05379; P = 0.001636). The results were similar to those of sensitivity analysis, and the sensitivity analysis also verified the conclusion. Furthermore, sensitivity and reverse MR analyses suggested that no heterogeneity, horizontal pleiotropy or reverse causality was found between RA and cardiovascular comorbidity. Conclusion: RA was noted to be causally associated with IHD and MI, rather than with AF and arrhythmia. This MR study might provide a new genetic basis for the causal relationship between RA and the risk of CVD. The findings suggested that the control of RA activity might reduce the risk of cardiovascular disease.
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BACKGROUND: Birth asphyxia causes hypoxia or inadequate perfusion to the organs of newborns, leading to metabolism dysfunctions including blood glucose disorders. METHODS: Neonates with and without birth asphyxia were retrospectively recruited from 53 hospitals in Hubei Province from January 1 to December 31, 2018. In summary, 875, 1139, and 180 cases in the control group, the mild asphyxia group, and the severe asphyxia group were recruited, respectively. Neonatal blood glucose values at postnatal 1, 2, 6, and 12 h (time error within 0.5 h was allowed) were gathered from the medical records. RESULTS: The incidence rates of hyperglycemia in the control group, the mild asphyxia group and the severe asphyxia group were 2.97%, 7.90%, and 23.33%, respectively (p < 0.001). Additionally, the incidence rates of hypoglycemia in the three groups above were 3.66%, 4.13%, and 7.78%, respectively (p = 0.042). The blood glucose values of neonates with hypoglycemia in the asphyxia group were lower than in the control group (p = 0.003). Furthermore, the blood glucose values of neonates with hyperglycemia were highest in the severe asphyxia group (p < 0.001). There were 778 and 117 cases with blood glucose records at four predefined time points in the mild and severe asphyxia group, respectively. The incidence of blood glucose disorders in the mild asphyxia group significantly decreased from postnatal 6 h (pï¼0.05). However, we found no obvious changes of the incidence of glucose disorders within postnatal 12 h in the severe asphyxia group (p = 0.589). CONCLUSION: Birth asphyxia is likely to cause neonatal blood glucose disorders, both hypoglycemia and hyperglycemia, during the early postnatal life. The neonates with severe asphyxia have higher incidence, worse severity and longer duration of blood glucose disorders than neonates with mild asphyxia.
Subject(s)
Asphyxia Neonatorum , Hyperglycemia , Hypoglycemia , Infant, Newborn, Diseases , Humans , Infant, Newborn , Blood Glucose , Asphyxia , Retrospective Studies , Asphyxia Neonatorum/epidemiology , Infant, Newborn, Diseases/epidemiology , Hypoglycemia/epidemiology , Hypoglycemia/etiology , Hyperglycemia/epidemiology , China/epidemiologyABSTRACT
OBJECTIVES@#To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia.@*METHODS@#A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively.@*RESULTS@#Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia.@*CONCLUSIONS@#The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Subject(s)
Infant, Newborn , Humans , Male , Pregnancy , Female , Nomograms , Retrospective Studies , Cesarean Section , Risk Factors , Asphyxia Neonatorum/etiologyABSTRACT
Background: As the population ages, there will be an increasing number of octogenarian patients with non-small cell lung cancer (NSCLC). In carefully selected elderly patients, surgery can improve long-term survival. To identify candidates who would benefit from surgery, we performed this study and built a predictive model. Materials and methods: Data from NSCLC patients over 80 years old were obtained from the Surveillance, Epidemiology and End Results database. A 1:1 propensity score matching was performed to balance the clinicopathological features between the surgery and non-surgery groups. Kaplan-Meier analyses and log-rank tests were used to assess the significance of surgery to outcome, and Cox proportional-hazards regression and competing risk model were conducted to determine the independent prognostic factors for these patients. A nomogram was built using multivariable logistic analyses to predict candidates for surgery based on preoperative factors. Results: The final study population of 31,462 patients were divided into surgery and non-surgery groups. The median cancer-specific survival time respectively was 53 vs. 13 months. The patients' age, sex, race, Tumor, Node, Metastasis score, stage, chemotherapy use, tumor histology and nuclear grade were independent prognostic factors. Apart from race and chemotherapy, other variates were included in the predictive model to distinguish the optimal surgical octogenarian candidates with NSCLC. Internal and external validation confirmed the efficacy of this model. Conclusion: Surgery improved the survival time of octogenarian NSCLC patients. A novel nomogram was built to help clinicians make the decision to perform surgery on elderly patients with NSCLC.
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BACKGROUND: This meta-analysis aimed to compare the potential effects of local anesthesia (LA) and general anesthesia (GA) for transcatheter aortic valve implantation (TAVI). MEASUREMENTS: All relevant studies were searched from Pubmed, EMbase, Web of Science, and the Cochrane Library (January 1, 2016, to June 1, 2021). The main outcomes of this literature meta-analysis were 30-day mortality, procedural time, new pacemaker implantation, total stay in the hospital, use of the vasoactive drug, and intra-and postoperative complications and emergencies, including conversion to open, myocardial infarction, pulmonary complication, vascular complication, renal injury/failure, stroke, transesophageal echocardiography, life-threatening/major bleeding, cardiac tamponade, and emergency PCI. Pooled risk ratio (RR) and mean difference (MD) together with a 95% confidence interval (CI) were calculated. RESULTS: A total of 17 studies, including 20938 patients, in the final analysis, fulfilled the inclusion criteria. Intra-and postoperative complications (myocardial infarction, vascular complication, renal injury/failure, stroke, and cardiac tamponade) undergoing TAVI in severe AS patients under GA do not offer a significant difference compared with LA. No differences were observed between LA and GA for new pacemaker implantation, total stay in the hospital, transesophageal echocardiography, and emergency PCI. LA has lower mortality compared with GA (RR 0.69, P = 0.600), pulmonary complications (RR 0.54, P = 0.278), life-threatening/major bleeding (RR 0.85, P = 0.855), and lower times of conversion to open (RR 0.22, P = 0.746). LA has many advantages, including a shorter procedure duration (MD=-0.38, P = 0.000) and reduction of the use of the vasoactive drug (RR 0.57, P = 0.000). CONCLUSIONS: For TAVI, both LA with or without sedation and GA are feasible and safe. LA appears a feasible alternative to GA for AS patients undergoing TAVI.
Subject(s)
Anesthesia, General , Anesthesia, Local , Transcatheter Aortic Valve Replacement , Aortic Valve Stenosis/diagnosis , Aortic Valve Stenosis/surgery , Cardiac Tamponade/surgery , Humans , Myocardial Infarction/surgery , Percutaneous Coronary Intervention , Postoperative Complications/epidemiology , Postoperative Complications/surgery , StrokeABSTRACT
Background: The members of the Chromobox (CBX) family are important epigenetic regulatory molecules with critical biological roles in many tumors. However, no study has analyzed or verified their role in lung adenocarcinoma (LUAD). Methods: UALCAN and Oncomine databases were used to analyze CBX expression in LUAD, and the cBioPortal database was used to analyze CBX genetic variations. The Kaplan-Meier plotter and UALCAN databases were used to identify molecules with prognostic value. Gene Ontology pathway, receiver operating characteristic curves, and tumor-infiltrating immune cell analyses were used to clarify the biological function of the CBX hub molecules. Paired tumor samples and lung adenocarcinoma cell lines were collected for molecular functional assays to validate the results of the bioinformatics analysis. Results: CBX3/5 may have a cancer-promoting effect and its expression is associated with a poor patient prognosis, while CBX7 shows an opposite trend. CBX3/5/7 can regulate signaling pathways, regulate tumor immune cell infiltration, and has diagnostic value. Molecular biology experiments show that CBX3/5 is highly expressed in LUAD patients; in vitro it promotes the proliferation and migration of the LUAD cell line and can regulate the expression of the corresponding cytokines. CBX7 has opposite effects. Conclusion: Our bioinformatics analysis and subsequent experimental verification confirmed the CBX family members acted as hub signaling molecules in LUAD. The results provide new potential targets for the diagnosis and treatment of this cancer.
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BACKGROUND: The optimal treatment for elderly patients with esophageal cancer (EC) remains controversial. In the present study, we aimed to investigate whether elderly patients with stage II-III EC could benefit from trimodal therapy. METHODS: The selected elderly patients with stage II-III EC between 2004 and 2015 were included in a retrospective cohort study from the Surveillance, Epidemiology, and End Results database. The patients were divided into two groups based on whether or not they underwent surgery. The inverse probability of treatment weighting (IPTW) analysis was used to balance the confounding factors between the two groups. The Cox regression analysis, the log-rank test, and the Kaplan-Meier curves were conducted to identify the survival benefits of different treatment regimes. RESULTS: A total of 1596 patients were included in this cohort study, in which 278 patients underwent surgery. In the combination of chemoradiotherapy and surgery group, there were more male patients, more patients aged between 75 and 79 years, and more married patients in the surgery group. Moreover, there were more patients with adenomatous carcinoma, more patients with a tumor size of less than 5 cm, and more patients with a T3 stage in the combination group. In the survival analysis, patients in the combination group had a longer overall survival (OS) and EC-specific survival (ECSS). After IPTW analysis, the survival analysis generated similar results. The competitive risk model found that our results were stable. There was still a significant difference in OS and ECSS between the combination group and chemoradiotherapy alone group for esophageal adenocarcinoma (p < 0.001). CONCLUSIONS: Elderly patients with stage II-III EC, especially those with adenocarcinoma, could benefit from the combination of surgery and chemoradiotherapy.
Subject(s)
Chemoradiotherapy , Esophageal Neoplasms/therapy , Esophagectomy , Aged , Combined Modality Therapy , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Female , Humans , Male , Neoplasm Staging , Prognosis , Retrospective Studies , SEER Program , Survival Rate , United StatesABSTRACT
BACKGROUND: With the knowledge of oligometastases, primary surgery plays an increasingly vital role in metastatic non-small cell lung cancer. We aimed to evaluate the survival benefit of primary surgery based on metastatic patterns. MATERIALS AND METHODS: The selected patients with stage IV extrathoracic metastatic (m1b) non-small cell lung cancer between 2010 and 2015 were included in a retrospective cohort study from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple imputation was used for the missing data. Patients were divided into 2 groups depending on whether surgery was performed. After covariate balancing propensity score (CBPS) weighting, multivariate Cox regression models and Kaplan-Meier survival curve were built to identify the survival benefit of different metastatic patterns. RESULTS: Surgery can potentially increase the overall survival (OS) (adjusted HR: 0.68, P < 0.001) of non-small cell lung cancer. The weighted 3-year OS in the surgical group was 16.9%, compared with 7.8% in the nonsurgical group. For single organ metastasis, surgery could improve the survival of metastatic non-small cell lung cancer. Meanwhile, no significant survival improvements in surgical group were observed in patients with multiple organ metastases. CONCLUSION: The surgical survival benefits for extrathoracic metastatic non-small cell lung cancer could be divided by metastatic pattern.
Subject(s)
Carcinoma, Non-Small-Cell Lung/epidemiology , Lung Neoplasms/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/surgery , Clinical Decision-Making , Disease Management , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Prognosis , SEER Program , Treatment Outcome , United States/epidemiology , Young AdultABSTRACT
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers worldwide, and its morbidity is exacerbated by the lack of early symptoms. Bioinformatics analyses enable discovery of differentially expressed genes and non-protein-coding RNAs of potential prognostic and/or therapeutic relevance in ESCC and other cancers. Using bioinformatics tools, we searched for dysregulated miRNAs in two ESCC microarray datasets from the Gene Expression Omnibus (GEO) database. After identification of three upregulated and five downregulated miRNAs shared between databases, protein-protein interaction (PPI) network analysis was used to identify the top 10 hub-gene targets. Thereafter, a miRNA-gene interaction network predicted that most hub genes are regulated by miR-196a-5p and miR-1-3p, which are respectively upregulated and downregulated in ESCC. Functional enrichment analyses in the GO and KEGG databases indicated the potential involvement of these miRNAs in tumorigenesis-related processes and pathways, while both differential expression and correlation with T stage were demonstrated for each miRNA in a cohort of ESCC patients. Overexpression showed that miR-196a-5p increased, whereas miR-1-3p attenuated, proliferation and invasion in human ESCC cell lines grown in vitro. These findings suggest miR-196a-5p and miR-1-3p jointly contribute to ESCC tumorigenesis and are potential targets for diagnosis and treatment.
Subject(s)
Esophageal Neoplasms/genetics , Esophageal Squamous Cell Carcinoma/genetics , Gene Expression Regulation, Neoplastic/genetics , Gene Regulatory Networks/genetics , MicroRNAs/genetics , Cell Transformation, Neoplastic/genetics , Computational Biology , Databases, Genetic , Down-Regulation/genetics , Gene Ontology , Humans , Microarray Analysis , Prognosis , Protein Interaction Maps , Up-Regulation/geneticsABSTRACT
BACKGROUND: The expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors. MATERIALS AND METHODS: We searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features. RESULTS: A total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28-3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43-3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58-151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53-3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67-8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57-2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70-2.31, P = 0.000). CONCLUSION: The low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.
Subject(s)
Biomarkers, Tumor/metabolism , CD36 Antigens/metabolism , Neoplasms/pathology , Humans , PrognosisABSTRACT
BACKGROUND: MicroRNA-135 (miR-135) is a well-known non-coding RNA that has been demonstrated to participate in tumorigenesis and cancer development; however, the clinical prognostic value of miR-135 in digestive system cancers remains controversial. This meta-analysis aims to explore the potential value of miR-135 as a prognostic marker for digestive system cancers. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible articles published before 31 August 2019. Stata 12.0 software was used to analyze the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates to access the prognostic value of miR-135 in digestive system cancers. We then used The Cancer Genome Atlas (TCGA) datasets to validate the meta-analysis results. Results A total of 1470 patients from 17 studies were included in this meta-analysis. The pooled results showed that enhanced miR-135 expression was significantly associated with poor OR (hazard ratio (HR): 1.790; 95% confidence interval (95% CI): 1.577-2.031; P=0.000), DFS (HR: 1.482; 95% CI: 0.914-2.403; P=0.110), and RFS (HR: 3.994; 95% CI: 1.363-11.697; P=0.012) in digestive system cancers. A sensitivity analysis confirmed the reliability of our findings, and no significant publication bias was observed. CONCLUSION: MiR-135 can be used as a novel biomarker for patients with digestive system cancers. We look forward to future large-scale clinical studies that will investigate the prognostic value of miR-135.
Subject(s)
Biomarkers, Tumor/genetics , Digestive System Neoplasms/genetics , MicroRNAs/genetics , Prognosis , Carcinogenesis/genetics , Digestive System Neoplasms/pathology , Disease-Free Survival , Gene Expression Regulation, Neoplastic/genetics , HumansABSTRACT
BACKGROUND: The family of tripartite motif (TRIM) proteins, which includes 80 known TRIM protein genes in humans, play a key role in cellular processes. TRIM59, a member of the TRIM family of proteins, has been reported to be involved in the carcinogenesis of multiple types of tumors. However, the prognostic value of TRIM59 in the survival of tumor patients remains controversial. We therefore conducted a meta-analysis to assess the prognostic significance of TRIM59 in cancer patients. MATERIALS AND METHODS: PubMed, Embase, VIP, CNKI and Wanfang Data were searched for eligible reports published before September 30, 2018. The hazard ratio (HR) and 95% confidence intervals (CIs) were adopted to estimate the association between TRIM59 and overall survival (OS). RESULTS: Six studies with 1584 patients were included to assess the effect. The results showed that high levels of TRIM59 were significantly associated with poor OS in cancer patients (HRâ=â1.43, 95%CI: 1.24-1.66, Pâ<â.001), indicating that higher TRIM59 expression could be an independent prognostic factor for poor survival in cancer patients. CONCLUSION: Our meta-analysis suggests that higher TRIM59 expression predicts poor prognosis in cancer patients, and it may therefore serve as a promising prognostic factor.