BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC...BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.展开更多
Heart failure(HF)is a leading cause of morbidity and mortality in the United States.[1]A chronically,disabling and debilitating condition,HF often results in hospital admission and subsequent readmission.[2]After hos-...Heart failure(HF)is a leading cause of morbidity and mortality in the United States.[1]A chronically,disabling and debilitating condition,HF often results in hospital admission and subsequent readmission.[2]After hos-pitalization,nearly 25%of older adults with HF are discharged to skilled nursing facilities(SNFs)for re-habilitation due to difficulties with functioning in-dependently.[3]Critically,patients with HF dis-charged to SNFs also show significantly higher rates of mortality.[2]Identifying factors that predict mortality among this important patient population,especially factors that could be addressed in the hospital setting,is an important step toward im-proving survivability among these patients.展开更多
基金Supported by the Ministry of Science and Technology,Taiwan,No.MOST 104-2314-B-016-010-MY2 and No.MOST 106-2320-B-016-018the Ministry of National Defense,Taiwan,No.MAB-107-075,No.MAB-108-057and No.MAB-109-061
文摘BACKGROUND It is evident that current clinical criteria are suboptimal to accurately estimate patient prognosis.Studies have identified epigenetic aberrant changes as novel prognostic factors for colorectal cancer(CRC).AIM To estimate whether a methylation gene panel in different clinical stages can reflect a different prognosis.METHODS We enrolled 120 CRC patients from Tri-Service General Hospital in Taiwan and used the candidate gene approach to select six genes involved in carcinogenesis pathways.Patients were divided into two groups based on the methylation status of the six evaluated genes,namely,the<3 aberrancy group and≥3 aberrancy group.Various tumor stages were divided into two subgroups(local and advanced stages)on the basis of the pathological type of the following tissues:Tumor and adjacent normal tissues(matched normal).We assessed DNA methylation in tumors and adjacent normal tissues from CRC patients and analyzed the association between DNA methylation with different cancer stages and the prognostic outcome including time to progression(TTP)and overall survival.RESULTS We observed a significantly increasing trend of hazard ratio as the number of hypermethylated genes increased both in normal tissue and tumor tissue.The 5-year TTP survival curves showed a significant difference between the≥3 aberrancy group and the<3 aberrancy group.Compared with the<3 aberrancy group,a significantly shorter TTP was observed in the≥3 aberrancy group.We further analyzed the interaction between CRC prognosis and different cancer stages(local and advanced)according to the methylation status of the selected genes in both types of tissues.There was a significantly shorter 5-year TTP for tumors at advanced stages with the promoter methylation status of selected genes than for those with local stages.We found an interaction between cancer stages and the promoter methylation status of selected genes in both types of tissues.CONCLUSION Our data provide a significant association between the methylation markers in normal tissues with advanced stage and prognosis of CRC.We recommend using these novel markers to assist in clinical decision-making.
基金funded by the U.S.Department of Veterans Affairssupported by VA Health Services Research and Development Center of Innovation in Long Term Services and Supports(CIN13–419)+4 种基金supported by National Institute on Aging grants R21AG061632,R01AG 065722,RF1AG061221,and R01AG062492partially supported by the VA HSRD Merit Reviews IRP 20-003 and IIR 14–293–2 for analyst time and resources to build and maintain the heart failure databasesupported by HSRD merit awards HX002572 and HX002534supported by NIMH R01MH124832partially supported by the VA Office of Academic Affiliation Advanced Fellowship in Health Services Research。
文摘Heart failure(HF)is a leading cause of morbidity and mortality in the United States.[1]A chronically,disabling and debilitating condition,HF often results in hospital admission and subsequent readmission.[2]After hos-pitalization,nearly 25%of older adults with HF are discharged to skilled nursing facilities(SNFs)for re-habilitation due to difficulties with functioning in-dependently.[3]Critically,patients with HF dis-charged to SNFs also show significantly higher rates of mortality.[2]Identifying factors that predict mortality among this important patient population,especially factors that could be addressed in the hospital setting,is an important step toward im-proving survivability among these patients.