scholarly journals Evaluating the presence of deregulated tumoral onco-microRNAs in serum-derived exosomes of gastric cancer patients as noninvasive diagnostic biomarkers

Bioimpacts ◽  
2021 ◽  
Author(s):  
Houman Kahroba ◽  
Nasser Samadi ◽  
Mostafa Mostafazadeh ◽  
Mohamad Saied Hejazi ◽  
Mohammad Reza Sadeghi ◽  
...  

Introduction: Exosomal microRNAs (miRNAs) are emerging diagnostic biomarkers for different types of cancers. We aim to detect gastric cancer (GC)-specific miRNAs in serum exosomes with diagnostic potential. Methods: A pair of 43 tumor and tumor-adjacent tissue biopsies obtained from GC patients, also 5 mL peripheral blood (following 12h fasting) were collected from the same patients and healthy controls (HCs). QIAGEN miRCURY LNA miRNA Focus PCR Panel applied to screen differentially expressed onco-miRNAs. The candidate miRNAs with the highest fold changes proceeded for validation by qRT-PCR in individuals. Results: We identified that exosomal miR-10a-5p, miR-19b-3p, miR-215-5p, and miR-18a-5p were significantly upregulated in GC patient’s exosomes in contrast to HCs exosomes, Roc curve analysis indicated area under the ROC curve (AUC) of 0.801, 0.721, 0.780 and 0.736 respectively. The Roc curve analysis for the combined signature of four exosomal miRNAs indicated AUC of 0.813. Also, Spearman's correlation coefficients indicated that the miRNA expression is highly correlated between tumor and exosome. Conclusion: Herein, we specifically identified four miRNAs in serum exosomes of GC patients for a diagnostic purpose which are directly associated with tumoral miRNA expression profile.

2021 ◽  
Author(s):  
Shenglan Huang ◽  
Dan Li ◽  
Lingling Zhuang ◽  
Liying Sun ◽  
Jianbing Wu

Abstract Background:Gastric cancer (GC) is one of the most common malignant tumors with a poor prognosis. Ferroptosis is a novel and distinct type of non-apoptotic cell death that is closely associated with metabolism, redox biology, and tumor prognosis. Recently, ferroptosis-related long non-coding RNAs (lncRNAs) have received increasing attention in predicting cancer prognosis. Thus, we aimed to construct an ferroptosis-related lncRNAs signature for predicting the prognosis of patients with gastric cancer.Methods:We built an ferroptosis-related lncRNA risk signature by using Cox regression based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. Cox regression was performed to explore whether the signature could be used as an independent factor. A nomogram was built involving the risk score and clinicopathological features. Furthermore, we explored the biological functions and immune states in two groups.Results:Eight ferroptosis-related lncRNAs were obtained for constructing the prognosis model in gastric cancer. Kaplan–Meier curve analysis revealed that patients in the high-risk group had worse survival than those in the low-risk group. The survival outcome was also appropriate for subgroup analysis, including age, sex, grade, and clinical stage. Multivariate Cox regression analysis and receiver operating characteristic (ROC) curve analysis demonstrated that the risk score was an independent prognostic factor and superior to traditional clinicopathological features in predicting GC prognosis. Next, we established a nomogram according to clinical parameters (age, sex, grade, and clinical stage) and risk score. All the verified results, including ROC curve analysis, calibration curve, and decision curve analysis, demonstrated that the nomogram could accurately predict the survival of patients with gastric cancer. Gene set enrichment analysis revealed that these lncRNAs were mainly involved in cell adhesion, cancer pathways, and immune function regulation.Conclusion: We established a novel ferroptosis-related prognostic risk signature including eight lncRNAs and constructed a nomogram to predict the prognosis of gastric cancer patients, which may improve prognostic predictive accuracy and guide individualized treatment for patients with GC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahui Pan ◽  
Xinyue Zhang ◽  
Xuedong Fang ◽  
Zhuoyuan Xin

BackgroundGastric cancer is one of the most serious gastrointestinal malignancies with bad prognosis. Ferroptosis is an iron-dependent form of programmed cell death, which may affect the prognosis of gastric cancer patients. Long non-coding RNAs (lncRNAs) can affect the prognosis of cancer through regulating the ferroptosis process, which could be potential overall survival (OS) prediction factors for gastric cancer.MethodsFerroptosis-related lncRNA expression profiles and the clinicopathological and OS information were collected from The Cancer Genome Atlas (TCGA) and the FerrDb database. The differentially expressed ferroptosis-related lncRNAs were screened with the DESeq2 method. Through co-expression analysis and functional annotation, we then identified the associations between ferroptosis-related lncRNAs and the OS rates for gastric cancer patients. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 17 ferroptosis-related lncRNAs. We also evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis, receiver operating characteristic (ROC) curve analysis, and decision curve analysis (DCA).ResultsA ferroptosis-related “lncRNA–mRNA” co-expression network was constructed. Functional annotation revealed that the FOXO and HIF-1 signaling pathways were dysregulated, which might control the prognosis of gastric cancer patients. Then, a ferroptosis-related gastric cancer prognostic signature model including 17 lncRNAs was constructed. Based on the RiskScore calculated using this model, the patients were divided into a High-Risk group and a low-risk group. The K-M survival curve analysis revealed that the higher the RiskScore, the worse is the obtained prognosis. The ROC curve analysis showed that the area under the ROC curve (AUC) of our model is 0.751, which was better than those of other published models. The multivariate Cox regression analysis results showed that the lncRNA signature is an independent risk factor for the OS rates. Finally, using nomogram and DCA, we also observed a preferable clinical practicality potential for prognosis prediction of gastric cancer patients.ConclusionOur prognostic signature model based on 17 ferroptosis-related lncRNAs may improve the overall survival prediction in gastric cancer.


2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Chih-Min Su ◽  
Chia-Te Kung ◽  
Sheng-Yuan Hsiao ◽  
Nai-Wen Tsai ◽  
Yun-Ru Lai ◽  
...  

Objective. As cell-free DNA levels in the pleural fluid and serum of parapneumonic pleural effusion (PPE) patients have not been thoroughly explored, we evaluated their diagnostic potential. Methods. Twenty-two PPE and 16 non-PPE patients were evaluated. Serum and pleural fluids were collected, and cell-free DNA was quantified. All biomarkers were assessed for correlation with days after admission. Receiver operating characteristic (ROC) curve analysis was used to determine diagnostic accuracy and optimal cut-off point. Results. Nuclear and mitochondrial DNA levels in the pleural fluid and nuclear DNA levels in serum of PPE patients were significantly higher than in those of the non-PPE patients. However, only cell-free DNA levels in pleural fluid correlated with days after admission among PPE patients (r= 0.464, 0.538, respectively). ROC curve analysis showed that nuclear and mitochondrial DNA in pleural fluid had AUCs of 0.945 and 0.889, respectively. With cut-off values of 134.9 and 17.8 ng/ml for nuclear and mitochondrial DNA in pleural fluid, respectively, 96% sensitivity and 81% specificity were observed for PPE diagnosis. Conclusion. Nuclear and mitochondrial DNA in pleural fluid possess PPE diagnostic potential and correlated with disease severity. Serum nuclear DNA could also be used to distinguish freshly admitted PPE patients (Day 1) from non-PPE patients, but with less accuracy.


2021 ◽  
Author(s):  
Guanghui Zhou ◽  
Yi Shan ◽  
Zhiwei Tang ◽  
Ruhua Chen ◽  
Yan Fen ◽  
...  

Abstract Background We aimed to evaluate the diagnostic value of Activin A levels in serum and pleural effusion on parapneumonic pleural effusion (PPE). Methods We collected serum and pleural effusion from 86 PPE and 37 non-PPE (NPPE) patients. Including Activin A, levels of biomarkers as lactate dehydrogenase (LDH), procalcitonin (PCT) and C-reactive protein (CRP) were measured. All factors were calculated for association with days after admission. The diagnostic potential of biomarkers on PPE was considered by receiver operating characteristic (ROC) curve analysis. Results Levels of Activin A in serum and pleural effusion of PPE patients were significantly higher than those of the NPPE patients. Moreover, concentrations of Activin A in pleural effusion showed a more obvious relevant days after admission. ROC curve analysis found that Activin A in pleural effusion had AUCs of 0.899 with 93% sensitivity and 84% specificity for PPE diagnosis. Conclusion Activin A in pleural effusion correlated with disease severity could act to diagnosis PPE.


2021 ◽  
Vol 8 ◽  
Author(s):  
Jianping Xiong ◽  
Haitao Hu ◽  
Wenzhe Kang ◽  
Hao Liu ◽  
Fuhai Ma ◽  
...  

Background: The Naples prognostic score (NPS) is established according to nutritional or inflammatory state, which has been identified as a new prognostic score for various malignant tumors. However, its prognosis prediction effect on gastric cancer (GC) patients is still unknown so far. The present work aimed to examine the NPS function in the prediction of GC prognosis.Methods: In this study, patients undergoing surgery with no preoperative therapy were retrospectively examined from June 2011 to August 2019. Typically, the total cholesterol level, serum albumin content, neutrophil-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were determined to calculate the NPS. Besides, the prognostic value of NPS was evaluated by survival analyses. Time-dependent receiver operating characteristic (t-ROC) curve analysis was also carried out to compare the prognostic value of the scoring systems.Results: Altogether 1,283 cases were enrolled into the present work. NPS was markedly related to age, gender, tumor size, body mass index, vascular invasion, perineural invasion, and pTNM stage. Upon multivariate analysis, NPS was identified as an independent prognostic factor for the prediction of overall survival (OS) (P < 0.001). In subgroup analyses stratified by adjuvant chemotherapy or surgery alone, NPS was still the independent prognostic factor for OS in both groups (both P < 0.001). Furthermore, NPS exhibited higher accuracy in the prediction of OS than additional prognostic factors, as revealed by the results of t-ROC curve analysis.Conclusions: NPS is a simple and useful scoring system that can be used to independently predict the survival of GC cases undergoing surgery.


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Santos ◽  
S Paula ◽  
I Almeida ◽  
H Santos ◽  
H Miranda ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (P) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. The Get With The Guidelines Heart Failure score (GWTG-HF) predicts in-hospital mortality (M) of P admitted with AHF. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF and to compare ACTION-ICU to GWTG-HF as predictors of in-hospital M (IHM), early M [1-month mortality (1mM)] and 1-month readmission (1mRA), using real-life data. Methods Based on a single-center retrospective study, data collected from P admitted in the Cardiology department with AHF between 2010 and 2017. P without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used chi-square, non-parametric tests, logistic regression analysis and ROC curve analysis. Results Among the 300 P admitted with AHF included, mean age was 67.4 ± 12.6 years old and 72.7% were male. Systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. ACTION-ICU score was 10.4 ± 2.3 and GWTG-HF was 41.7 ± 9.6. Inotropes’ usage was necessary in 32.7% of the P, 11.3% of the P needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the P were readmitted 1 month after discharge. Older age (p < 0.001), lower SBP (p = 0,035) and need of inotropes (p < 0.001) were predictors of IHM in our population. As expected, patients presenting in KKC 4 had higher IHM (OR 8.13, p < 0.001). Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p < 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the variables were predictive of IV. LVEF (OR 0.924, p < 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p < 0.001, CI 0.971-0.988), higher urea (OR 1.01, p < 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors of inotropes’ usage. Logistic regression showed that GWTG-HF predicted IHM (OR 1.12, p < 0.001, CI 1.05-1.19), 1mM (OR 1.10, p = 1.10, CI 1.04-1.16) and inotropes’s usage (OR 1.06, p < 0.001, CI 1.03-1.10), however it was not predictive of 1mRA, need of IV or NIV. Similarly, ACTION-ICU predicted IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed that GWTG-HF score performed better than ACTION-ICU regarding IHM (AUC 0.774, CI 0.46-0-90 vs AUC 0.731, CI 0.59-0.88) and 1mM (AUC 0.727, CI 0.60-0.85 vs AUC 0.707, CI 0.58-0.84). Conclusion In our population, both scores were able to predict IHM, 1mM and inotropes’s usage.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuichiro Shimoyama ◽  
Osamu Umegaki ◽  
Noriko Kadono ◽  
Toshiaki Minami

Abstract Objective Sepsis is a major cause of mortality for critically ill patients. This study aimed to determine whether presepsin values can predict mortality in patients with sepsis. Results Receiver operating characteristic (ROC) curve analysis, Log-rank test, and multivariate analysis identified presepsin values and Prognostic Nutritional Index as predictors of mortality in sepsis patients. Presepsin value on Day 1 was a predictor of early mortality, i.e., death within 7 days of ICU admission; ROC curve analysis revealed an AUC of 0.84, sensitivity of 89%, and specificity of 77%; and multivariate analysis showed an OR of 1.0007, with a 95%CI of 1.0001–1.0013 (p = 0.0320).


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiajia Liu ◽  
Xiaoyi Tian ◽  
Yan Wang ◽  
Xixiong Kang ◽  
Wenqi Song

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaohua Ban ◽  
Xinping Shen ◽  
Huijun Hu ◽  
Rong Zhang ◽  
Chuanmiao Xie ◽  
...  

Abstract Background To determine the predictive CT imaging features for diagnosis in patients with primary pulmonary mucoepidermoid carcinomas (PMECs). Materials and methods CT imaging features of 37 patients with primary PMECs, 76 with squamous cell carcinomas (SCCs) and 78 with adenocarcinomas were retrospectively reviewed. The difference of CT features among the PMECs, SCCs and adenocarcinomas was analyzed using univariate analysis, followed by multinomial logistic regression and receiver operating characteristic (ROC) curve analysis. Results CT imaging features including tumor size, location, margin, shape, necrosis and degree of enhancement were significant different among the PMECs, SCCs and adenocarcinomas, as determined by univariate analysis (P < 0.05). Only lesion location, shape, margin and degree of enhancement remained independent factors in multinomial logistic regression analysis. ROC curve analysis showed that the area under curve of the obtained multinomial logistic regression model was 0.805 (95%CI: 0.704–0.906). Conclusion The prediction model derived from location, margin, shape and degree of enhancement can be used for preoperative diagnosis of PMECs.


2019 ◽  
Vol 11 ◽  
pp. 1759720X1988555 ◽  
Author(s):  
Wanlong Wu ◽  
Jun Ma ◽  
Yuhong Zhou ◽  
Chao Tang ◽  
Feng Zhao ◽  
...  

Background: Infection remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). This study aimed to establish a clinical prediction model for the 3-month all-cause mortality of invasive infection events in patients with SLE in the emergency department. Methods: SLE patients complicated with invasive infection admitted into the emergency department were included in this study. Patient’s demographic, clinical, and laboratory characteristics on admission were retrospectively collected as baseline data and compared between the deceased and the survivors. Independent predictors were identified by multivariable logistic regression analysis. A prediction model for all-cause mortality was established and evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 130 eligible patients were collected with a cumulative 38.5% 3-month mortality. Lymphocyte count <800/ul, urea >7.6mmol/l, maximum prednisone dose in the past ⩾60 mg/d, quick Sequential Organ Failure Assessment (qSOFA) score, and age at baseline were independent predictors for all-cause mortality (LUPHAS). In contrast, a history of hydroxychloroquine use was protective. In a combined, odds ratio-weighted LUPHAS scoring system (score 3–22), patients were categorized to three groups: low-risk (score 3–9), medium-risk (score 10–15), and high-risk (score 16–22), with mortalities of 4.9% (2/41), 45.9% (28/61), and 78.3% (18/23) respectively. ROC curve analysis indicated that a LUPHAS score could effectively predict all-cause mortality [area under the curve (AUC) = 0.86, CI 95% 0.79–0.92]. In addition, LUPHAS score performed better than the qSOFA score alone (AUC = 0.69, CI 95% 0.59–0.78), or CURB-65 score (AUC = 0.69, CI 95% 0.59–0.80) in the subgroup of lung infections ( n = 108). Conclusions: Based on a large emergency cohort of lupus patients complicated with invasive infection, the LUPHAS score was established to predict the short-term all-cause mortality, which could be a promising applicable tool for risk stratification in clinical practice.


Sign in / Sign up

Export Citation Format

Share Document