scholarly journals Profiles of autophagy-related genes in esophageal adenocarcinoma

2020 ◽  
Author(s):  
Lei Zhu ◽  
Lin Dong ◽  
Fugui Yang ◽  
Qinchuan Li

Abstract Background: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. Results: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR=0.321, P=0.046), DAPK1 (HR=0.636, P=0.025) and CAPN1 (HR=0.395, P=0.004) played protective roles in survival. Gender (HR=0.225, P=0.032), stage (HR=5.841, P=0.008) and risk score (HR=1.131, P<0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P <0.05). Conclusion: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.

2020 ◽  
Author(s):  
Lei Zhu ◽  
Lin Dong ◽  
Minghao Feng ◽  
Fugui Yang ◽  
Wenhao Jiang ◽  
...  

Abstract Background: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues. Results: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR=0.321, P=0.046), DAPK1 (HR=0.636, P=0.025) and CAPN1 (HR=0.395, P=0.004) played protective roles in survival. Gender (HR=0.225, P=0.032), stage (HR=5.841, P=0.008) and risk score (HR=1.131, P<0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P <0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P<0.05). Conclusion: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.


2020 ◽  
Author(s):  
Lei Zhu ◽  
Lin Dong ◽  
Minghao Feng ◽  
Fugui Yang ◽  
Wenhao Jiang ◽  
...  

Abstract Background: Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients.Methods: Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues.Results: Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR=0.321, P=0.046), DAPK1 (HR=0.636, P=0.025) and CAPN1 (HR=0.395, P=0.004) played protective roles in survival. Gender (HR=0.225, P=0.032), stage (HR=5.841, P=0.008) and risk score (HR=1.131, P<0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P <0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P<0.05).Conclusion: Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Lei Zhu ◽  
Lin Dong ◽  
Minghao Feng ◽  
Fugui Yang ◽  
Wenhao Jiang ◽  
...  

Abstract Background Several studies have demonstrated autophagy was involved in the process of esophageal adenocarcinoma (EAC). The aim of this study was to explore autophagy-related genes (ARGs) correlated with overall survival (OS) in EAC patients. Methods Expressions of ARGs in EAC and normal samples were downloaded from TCGA database. GO and KEGG enrichment analyses were used to investigate the ARGs bioinformatics functions. Univariate and multivariate cox regressions were performed to identify prognostic ARGs and the independent risk factors. ROC curve was established to evaluate the feasibility to predict the prognosis. Finally, the correlations between ARGs and clinical features were further explored. In addition, significantly different ARGs were verified in EAC specimens and normal esophageal mucosal tissues. Results Thirty significantly different ARGs were selected from EAC and normal tissues. Functional enrichments showed these ARGs were mainly related apoptosis. Multivariate cox regression analyses demonstrated eight ARGs were significantly associated with OS. Among these eight genes, BECN1 (HR = 0.321, P = 0.046), DAPK1 (HR = 0.636, P = 0.025) and CAPN1 (HR = 0.395, P = 0.004) played protective roles in survival. Gender (HR = 0.225, P = 0.032), stage (HR = 5.841, P = 0.008) and risk score (HR = 1.131, P < 0.001) were independent prognostic risk factors. ROC curves showed better efficacy to predict survival using the risk score. Additionally, we found BECN1, DAPK1, VAMP7 and SIRT1 genes were correlated significantly with survival status, gender, primary tumor and tumor stage (all P < 0.05). The experimental results confirmed the BIRC5 was overexpressed and the ITPR1, PRKN were downregulated in the EAC tissues compared with the normal esophageal mucosal tissues (all P < 0.05). Conclusion Our findings suggested that autophagy was involved in the process of EAC. Several ARGs probably could serve as diagnostic and prognostic biomarkers and may help facilitate therapeutic targets in EAC patients.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9173 ◽  
Author(s):  
Weiwei Gui ◽  
Weifen Zhu ◽  
Weina Lu ◽  
Chengxin Shang ◽  
Fenping Zheng ◽  
...  

Background Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor with a poor prognosis. However, there is no useful clinical prognostic predictive tool for ATC so far. Our study identified risk factors for survival of ATC and created a reliable nomogram to predict overall survival (OS) and cancer-specific survival (CSS) of patients with ATC. Methods A total of 1,404 cases of ATC diagnosed between 1983 and 2013 were extracted from on the Surveillance, Epidemiology and End Results database based on our inclusion criteria. OS and CSS were compared among patients between each variable by Kaplan–Meier methods. The Cox proportional hazards model was used to evaluate multiple prognostic factors and obtain independent predictors. All independent risk factors were included to build nomograms, whose accuracy and practicability were tested by concordance index (C-index), calibration curves, ROC curves, DCA, net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Results Historic stage, tumor size, surgery and radiotherapy were independent risk factors associated with ATC according to multivariate Cox regression analysis of OS. However, gender was also an important prognostic predictor in CSS besides the factors mentioned above. These characteristics were included in the nomograms predicting OS and CSS of patients with ATC. The nomograms predicting OS and CSS performed well with a C-index of 0.765 and 0.773. ROC curves, DCA, NRI and IDI suggested that the nomogram was superior to TNM staging and age. Conclusion The proposed nomogram is a reliable tool based on the prediction of OS and CSS for patients with ATC. Such a predictive tool can help to predict the survival of the patients.


2020 ◽  
Author(s):  
Dan Wang ◽  
Ruihua Shi ◽  
Xinlin Shi ◽  
Wei Xu

Abstract Purpose: To create an effective survival nomogram for patients with primary gastric mucosa‐associated lymphoid tissue (MALT) lymphoma (GML).Methods. All data of patients with primary GML from 2004 to 2015 were collected from the Surveillance, Epidemiology and End Results (SEER) database. The primary endpoint was overall survival (OS). Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves.Results. A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 months, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all p<0.05). The C-index values of the nomogram were 0.751 (95% CI: 0.729-0.773) and 0.718 (95% CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML.Conclusions. A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.


2021 ◽  
Vol 108 (Supplement_1) ◽  
Author(s):  
SJ Tingle ◽  
ER Thompson ◽  
SS Ali ◽  
IK Ibrahim ◽  
E Irwin ◽  
...  

Abstract Introduction Biliary leaks and anastomotic strictures are common early biliary complications (EBC) following liver transplantation. However, their impact on outcomes remains controversial and poorly described. Method The NHS registry on adult liver transplantation between 2006 and 2017 was retrospectively reviewed (n=8304). Multiple imputations were performed to account for missing data. Adjusted regression models were used to assess predictors of EBC, and their impact on outcomes. 35 potential variables were included, and backwards stepwise selection enabled unbiased selection of variables for inclusion in final models. Result EBC occurred in 9.6% of patients. Adjusted cox regression revealed that EBCs have a significant and independent impact on graft survival (Leak HR=1.325; P=0.021, Stricture HR=1.514; P=0.002, Leak plus stricture HR=1.533; P=0.034) and patient survival (Leak HR=1.218; P=0.131, Stricture HR=1.578; P&lt;0.001, Leak plus stricture HR=1.507; P=0.044). Patients with EBC had longer median hospital stay (23 versus 15 days; P&lt;0.001) and increased chance for readmission within the first year (56% versus 32%; P&lt;0.001). On adjusted logistic regression the following were identified as independent risk factors for development of EBC: donation following circulatory death (OR=1.280; P=0.009), accessory hepatic artery (OR=1.324; P=0.005), vascular anastomosis time in minutes (OR=1.005; P=0.032) and ethnicity ‘other’ (OR=1.838; P=0.011). Conclusion EBCs prolong hospital stay, increase readmission rates and are independent risk factors for diminished graft survival and increased mortality in liver transplantation. We have identified factors that increase the likelihood of EBC occurrence; further research into interventions to prevent EBCs in these at-risk groups is vital to improve liver transplantation outcomes. Take-home message Using a large registry database we have shown that early anastomotic biliary complications are independent risk factors for decreased graft survival and increased mortality after liver transplantation. Research into interventions to prevent biliary complications in high risk groups are essential to improve liver transplant outcomes.


Author(s):  
Koichi Tomita ◽  
Itsuki Koganezawa ◽  
Masashi Nakagawa ◽  
Shigeto Ochiai ◽  
Takahiro Gunji ◽  
...  

Abstract Background Postoperative complications are not rare in the elderly population after hepatectomy. However, predicting postoperative risk in elderly patients undergoing hepatectomy is not easy. We aimed to develop a new preoperative evaluation method to predict postoperative complications in patients above 65 years of age using biological impedance analysis (BIA). Methods Clinical data of 59 consecutive patients (aged 65 years or older) who underwent hepatectomy at our institution between 2017 and 2020 were retrospectively analyzed. Risk factors for postoperative complications (Clavien-Dindo ≥ III) were evaluated using multivariate regression analysis. Additionally, a new preoperative risk score was developed for predicting postoperative complications. Results Fifteen patients (25.4%) had postoperative complications, with biliary fistula being the most common complication. Abnormal skeletal muscle mass index from BIA and type of surgical procedure were found to be independent risk factors in the multivariate analysis. These two variables and preoperative serum albumin levels were used for developing the risk score. The postoperative complication rate was 0.0% with a risk score of ≤ 1 and 57.1% with a risk score of ≥ 4. The area under the receiver operating characteristic curve of the risk score was 0.810 (p = 0.001), which was better than that of other known surgical risk indexes. Conclusion Decreased skeletal muscle and the type of surgical procedure for hepatectomy were independent risk factors for postoperative complications after elective hepatectomy in elderly patients. The new preoperative risk score is simple, easy to perform, and will help in the detection of high-risk elderly patients undergoing elective hepatectomy.


2021 ◽  
Vol 20 ◽  
pp. 153303382110279
Author(s):  
Qinping Guo ◽  
Yinquan Wang ◽  
Jie An ◽  
Siben Wang ◽  
Xiushan Dong ◽  
...  

Background: The aim of our study was to develop a nomogram model to predict overall survival (OS) and cancer-specific survival (CSS) in patients with gastric signet ring cell carcinoma (GSRC). Methods: GSRC patients from 2004 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database and randomly assigned to the training and validation sets. Multivariate Cox regression analyses screened for OS and CSS independent risk factors and nomograms were constructed. Results: A total of 7,149 eligible GSRC patients were identified, including 4,766 in the training set and 2,383 in the validation set. Multivariate Cox regression analysis showed that gender, marital status, race, AJCC stage, TNM stage, surgery and chemotherapy were independent risk factors for both OS and CSS. Based on the results of the multivariate Cox regression analysis, prognostic nomograms were constructed for OS and CSS. In the training set, the C-index was 0.754 (95% CI = 0.746-0.762) for the OS nomogram and 0.762 (95% CI: 0.753-0.771) for the CSS nomogram. In the internal validation, the C-index for the OS nomogram was 0.758 (95% CI: 0.746-0.770), while the C-index for the CSS nomogram was 0.762 (95% CI: 0.749-0.775). Compared with TNM stage and SEER stage, the nomogram had better predictive ability. In addition, the calibration curves also showed good consistency between the predicted and actual 3-year and 5-year OS and CSS. Conclusion: The nomogram can effectively predict OS and CSS in patients with GSRC, which may help clinicians to personalize prognostic assessments and clinical decisions.


2021 ◽  
Author(s):  
Denghui Wang ◽  
Jiang Zhu ◽  
Chang Deng ◽  
Zhixin Yang ◽  
Daixing Hu ◽  
...  

Abstract Objective: Few studies have evaluated the influence of HT and Multifocality on central lymph node metastases(CLNM) and lateral lymph node metastases(LLNM) of PTC. The present study focused on risk factors for lymph node metastasis in PTC according to the presence of HT or multifocality. Materials and methods:1413 patients were identified.The relationship between HT or multifocality and lymph nodemetastasis was analyzed by univariate and multivariate logistic regression, ROC curves were constructed to show the predictive effect of each variable on the target outcome.Results: The PTCs with HT were more likely to be multifocal.(40.0% versus 17.5%,P <0.001). Compared to MPTC without HT, MPTC with HT showed a lower number of metastatic CLNs and LLNs (P < 0.05). HT was identifified as an independent protective factor for CLNM in all PTC patients (OR, 0.480; 95% CI, 0.359-0.643; P< .001) and in MPTC patients (OR, 0.094; 95% CI, 0.044-0.204; P < 0.001), the multicocality was independent risk factors for CLNM(OR, 2.316; 95% CI, 1.667-3.217; P< 0.001) and LLNM(OR, 2.004; 95% CI, 1.469-2.733; P< 0.001).The variables concluded HT or MPTC were screened to predict CLNM in all patients, CLNM in patients with MPTC and LLNM in all patients (AUCs: 0.731, 0.843 and 0.696, respectively, P < 0.0001). The two type of diseases existed concurrently may result in the decrease of CLNM and LLNM, AUCs of ROC to predict CLNM and LLNM are 0.696 and 0.63(P<0.0001). Conclusions: Our study identified multifocality as an independent risk factor predicting CLNM and LLNM in PTC patients. HT was proven to be a protective factor that reduced the CLNM risk in all patients and in patients with MPTC. The existence of both type of diseases can result in the reduction of CLNM and LLNM.


2010 ◽  
Vol 30 (4) ◽  
pp. 440-447 ◽  
Author(s):  
Jie Dong ◽  
Yuan Chen

ObjectiveWe studied whether improper bag exchange predicts the first peritonitis episode in continuous ambulatory peritoneal dialysis (CAPD) patients.Patients and MethodsOur single-center prospective observational study of 130 incident urban CAPD patients who started peritoneal dialysis (PD) between March 2005 and August 2008 aimed to determine the relationship between bag exchange procedures examined at the 6th month of PD and risk for a first peritonitis episode. All patients were followed until a first peritonitis episode, censoring, or the end of the study.ResultsThese 130 patients experienced 22 first peritonitis episodes during the 14-month follow-up. During bag exchange evaluation, 51.5% of patients washed their hands improperly, 46.2% failed to check expiration date or bag leakage, and 11.5% forgot to wear a face mask and cap. Patients experiencing peritonitis were more likely to forget to wear a face mask and cap. In multivariate Cox regression model, not wearing a face mask and cap [hazard ratio (HR): 7.26; 95% confidence interval (CI): 2.6 to 20.1; p < 0.001] and having anemia (HR: 0.96; 95% CI: 0.94 to 0.99; p = 0.005) were independent risk factors for a first episode of peritonitis.ConclusionsNot wearing a face mask and cap and having anemia were independent risk factors for peritonitis. A further randomized control study needs to verify the correlation between improper bag exchange technique and peritonitis in PD patients.


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