BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop ...BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.展开更多
BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical valu...BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.展开更多
Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkin-sonism(AR-JP)via Parkin mutations and that the Parkin protein is the core expression product of the P...Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkin-sonism(AR-JP)via Parkin mutations and that the Parkin protein is the core expression product of the Parkin gene,which itself belongs to an E3 ubiquitin ligase.Since the discovery of the Parkin gene in the late 1990s,researchers in many countries have begun extensive research on this gene and found that in addition to AR-JP,the Parkin gene is associated with many diseases,including type 2 diabetes,leprosy,Alzheimer’s,autism,and cancer.Recent studies have found that the loss or dysfunction of Parkin has a certain relationship with tumorigenesis.In general,the Parkin gene,a well-established tumor suppressor,is deficient and mutated in a variety of malignancies.Parkin overexpres-sion inhibits tumor cell growth and promotes apoptosis.However,the functions of Parkin in tumorigenesis and its regulatory mechanisms are still not fully understood.This article describes the structure,functions,and post-transla-tional modifications of Parkin,and summarizes the recent advances in the tumor suppressive function of Parkin and its underlying mechanisms.展开更多
Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcr...Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.展开更多
Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcr...Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.展开更多
文摘BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative survival.AIM To investigate the prognosis of GMA and develop predictive model.METHODS From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with GMA.After random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s prognosis.RESULTS This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test cohort.We packaged it into Windows software for doctors’use and uploaded it.Mucinous gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P<0.001]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P<0.001).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA postoperatively.Combining surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.
基金the National Natural Science Foundation of China,No.81960504the“Xingdian Talents”Support Project of Yunnan Province,No.RLQB20200002+2 种基金the Medical Discipline Reserve Talents of Yunnan Province,No.H-2018015the Applied Basic Research Projects-Union Foundation of Kunming Medical University,No.2017FE467(-132)the Talent Introduction Project of Hubei Polytechnic University,No.21xjz34R。
文摘BACKGROUND Aberrant methylation is common during the initiation and progression of colorectal cancer(CRC),and detecting these changes that occur during early adenoma(ADE)formation and CRC progression has clinical value.AIM To identify potential DNA methylation markers specific to ADE and CRC.METHODS Here,we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape.RESULTS Comparing 22 CRC and 25 ADE samples,global methylation was higher in the former,but both showed similar methylation patterns regarding differentially methylated gene positions,chromatin signatures,and repeated elements.High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC.Combined with RNA-seq gene expression data,we identified 14 methylation-regulated differentially expressed genes,of which only AGTR1 and NECAB1 methylation had prognostic significance.CONCLUSION Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC,suggesting prognostic biomarkers for CRC.
基金This work was supported by the National Natural Science Foundation of China(81622005)Beijing Natural Science Foundation(7172213).
文摘Clinical practice has shown that Parkin is the major causative gene found in an autosomal recessive juvenile parkin-sonism(AR-JP)via Parkin mutations and that the Parkin protein is the core expression product of the Parkin gene,which itself belongs to an E3 ubiquitin ligase.Since the discovery of the Parkin gene in the late 1990s,researchers in many countries have begun extensive research on this gene and found that in addition to AR-JP,the Parkin gene is associated with many diseases,including type 2 diabetes,leprosy,Alzheimer’s,autism,and cancer.Recent studies have found that the loss or dysfunction of Parkin has a certain relationship with tumorigenesis.In general,the Parkin gene,a well-established tumor suppressor,is deficient and mutated in a variety of malignancies.Parkin overexpres-sion inhibits tumor cell growth and promotes apoptosis.However,the functions of Parkin in tumorigenesis and its regulatory mechanisms are still not fully understood.This article describes the structure,functions,and post-transla-tional modifications of Parkin,and summarizes the recent advances in the tumor suppressive function of Parkin and its underlying mechanisms.
基金supported by the National Key Research and Development Program of China(2020YFC0842000 to Y.T.Z.)the Yunnan Provincial major science and technology special project(202003AC100007 to X.Q.D.).
文摘Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.
基金This work was supported by the National Key Research and Development Program of China(2020YFC0842000 to Y.T.Z.)the Yunnan Provincial major science and technology special project(202003AC100007 to X.Q.D.).
文摘Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.