BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive to...BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.展开更多
Background:The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer(CRC).Published data on gene fusions are limited by relatively small sample sizes,with a primary focus on Western ...Background:The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer(CRC).Published data on gene fusions are limited by relatively small sample sizes,with a primary focus on Western populations.This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.Methods:This study included 5,534 consecutive CRC patients from the Genecast database.Genomic profiling was performed using a panel of 769 cancer-related genes.Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.Results:Among 5,534 CRC patients,54(0.98%)had actionable gene fusions,with NTRK1/2/3 being the most common fusion(0.38%),accounting for 38.9%(21/54)of those with fusions.Actionable gene fusion enrichment was higher in patients with microsatellite instability-high(MSI-H)(6.7%vs.0.5%,P<0.001),RAS/BRAF wildtype(2.0%vs.0.2%,P<0.001)and RNF43 mutation(7.7%vs.0.4%,P<0.001)than in patients with microsatellite stability/MSI-low,RAS/BRAF mutation and RNF43 wildtype,respectively.When these markers were combined,the fusion detection rate increased.Among patients with RAS/BRAF wildtype and MSI-H,fusions were detected in 20.3%of patients.The fusion detection rate further increased to 37.5%when RNF43 mutation was added.The fusion detection rate was also higher in colon cancer than in rectal cancer.No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast,cBioPortal,and ChimerSeq databases.Conclusions:Approximately 1%of the unselected Chinese CRC population carries actionable gene fusions,mostly involving NTRK.Actionable gene fusions are more prevalent in MSI-H,RAS/BRAF wildtype,or RNF43-mutated CRC,as well as in colon cancer.Mapping of these molecular markers can markedly increase the fusion detection rate,which can help clinicians select candidates for fusion testing and targeted therapy.展开更多
文摘BACKGROUND Signet ring cell carcinoma(SRCC)is an uncommon subtype in colorectal cancer(CRC),with a short survival time.Therefore,it is imperative to establish a useful prognostic model.As a simple visual predictive tool,nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years.Until now,there has been no nomogram to predict the outcome of CRC patients with SRCC.AIM To build effective nomograms for predicting overall survival(OS)and causespecific survival(CSS)of CRC patients with SRCC.METHODS Data were extracted from the Surveillance,Epidemiology,and End Results database between 2004 and 2015.Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms.Performance of the nomograms was assessed by concordance index,calibration curves,and receiver operating characteristic(ROC)curves.ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis(TNM)staging system.Patients were classified as high-risk,moderate-risk,and low-risk groups using the novel nomograms.Kaplan-Meier curves were plotted to compare survival differences.RESULTS In total,1230 patients were included.The concordance index of the nomograms for OS and CSS were 0.737(95%confidence interval:0.728-0.747)and 0.758(95%confidence interval:0.738-0.778),respectively.The calibration curves and ROC curves demonstrated good predictive accuracy.The 1-,3-,and 5-year area under the curve values of the nomogram for predicting OS were 0.796,0.825 and 0.819,in comparison to 0.743,0.798,and 0.803 for the TNM staging system.In addition,the 1-,3-,and 5-year area under the curve values of the nomogram for predicting CSS were 0.805,0.847 and 0.863,in comparison to 0.740,0.794,and 0.800 for the TNM staging system.Based on the novel nomograms,stratified analysis showed that the 5-year probability of survival in the high-risk,moderate-risk,and low-risk groups was 6.8%,37.7%,and 67.0%for OS(P<0.001),as well as 9.6%,38.5%,and 67.6%for CSS(P<0.001),respectively.CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC,which are superior to the conventional TNM staging system.
基金supported by the capital health research and development of special(2022-2-7083).
文摘Background:The prevalence of gene fusion is extremely low in unselected patients with colorectal cancer(CRC).Published data on gene fusions are limited by relatively small sample sizes,with a primary focus on Western populations.This study aimed to analyse actionable gene fusions in a large consecutive Chinese CRC population.Methods:This study included 5,534 consecutive CRC patients from the Genecast database.Genomic profiling was performed using a panel of 769 cancer-related genes.Data for 34 CRC patients with actionable gene fusions were also collected from cBioPortal and ChimerSeq.Results:Among 5,534 CRC patients,54(0.98%)had actionable gene fusions,with NTRK1/2/3 being the most common fusion(0.38%),accounting for 38.9%(21/54)of those with fusions.Actionable gene fusion enrichment was higher in patients with microsatellite instability-high(MSI-H)(6.7%vs.0.5%,P<0.001),RAS/BRAF wildtype(2.0%vs.0.2%,P<0.001)and RNF43 mutation(7.7%vs.0.4%,P<0.001)than in patients with microsatellite stability/MSI-low,RAS/BRAF mutation and RNF43 wildtype,respectively.When these markers were combined,the fusion detection rate increased.Among patients with RAS/BRAF wildtype and MSI-H,fusions were detected in 20.3%of patients.The fusion detection rate further increased to 37.5%when RNF43 mutation was added.The fusion detection rate was also higher in colon cancer than in rectal cancer.No significant differences in clinical or molecular features were found in patients with actionable gene fusions between the Genecast,cBioPortal,and ChimerSeq databases.Conclusions:Approximately 1%of the unselected Chinese CRC population carries actionable gene fusions,mostly involving NTRK.Actionable gene fusions are more prevalent in MSI-H,RAS/BRAF wildtype,or RNF43-mutated CRC,as well as in colon cancer.Mapping of these molecular markers can markedly increase the fusion detection rate,which can help clinicians select candidates for fusion testing and targeted therapy.
