Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) resi...Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes ( P = 0.046 and P = 0.048). Pa- tients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs ( P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mu- tations with pre-treatment CTCs compared with post-treatment CTCs. Conclusions: Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.展开更多
Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden...Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden,including the Global cancer statistics 2018 and Cancer statistics in China,2015,along with the GLOBCAN 2018 online database,to investigate the differences of cancer patterns between China,the United States(USA)and the United Kingdom(UK).An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018.Compared to the USA and UK,China has lower cancer incidence but a 30%and 40%higher cancer mortality than the UK and USA,among which 36.4%of the cancer-related deaths were from the digestive tract cancers(stomach,liver,and esophagus cancer)and have relatively poorer prognoses.In comparison,the digestive cancer deaths only took up≤5%of the total cancer deaths in either USA or UK.Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions.China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country,with a rapidly increase cancer burden of colorectal,prostate,female breast cancers in addition to a high occurrence of infection-related and digestive cancers.The incidence of westernized lifestyle-related cancers in China(i.e.colorectal cancer,prostate,bladder cancer)has risen but the incidence of the digestive cancers has decreased from 2000 to 2011.An estimated 40%of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries.Tobacco smoking is the single most important carcinogenic risk factor in China,contributing to~24.5%of cancers in males.Chronic infection is another important preventable cancer contributor which is responsible for~17%of cancers.Comprehensive prevention and control strategies in China should include effective tobacco-control policy,recommendations for healthier lifestyles,along with enlarg-ing the coverage of effective screening,educating,and vaccination programs to better sensitize greater awareness control to the general public.展开更多
Background:Cancer is one of the leading causes of death and a main economic burden in China.Investigating the differences in cancer patterns and control strategies between China and developed countries could provide r...Background:Cancer is one of the leading causes of death and a main economic burden in China.Investigating the differences in cancer patterns and control strategies between China and developed countries could provide reference for policy planning and contribute to improving cancer control measures.In this study,we reviewed the rates and trends of cancer incidence and mortality and disability-adjusted life year(DALY)burden in China,and compared them with those in the United States(US)and the United Kingdom(UK).Methods:Cancer incidence,mortality,and DALY data for China,US and UK were obtained fromtheGLOBOCAN2020 online database,Global Burden of Disease(GBD)2019 study,and Cancer Incidence in Five Continents plus database(CI5 plus).Trends of cancer incidence and mortality in China,US,and UK were analyzed using Joinpoint regression models to calculate annual percent changes(APCs)and identify the best-fitting joinpoints.Results:An estimated 4,568,754 newly diagnosed cancer cases and 3,002,899 cancer deaths occurred in China in 2020.Additionally,cancers resulted in 67,340,309 DALYs in China.Compared to the US and UK,China had lower cancer incidence but higher cancer mortality andDALY rates.Furthermore,the cancer spectrum of China was changing,with a rapid increase incidence and burden of lung,breast,colorectal,and prostate cancer in addition to a high incidence and heavy burden of liver,stomach,esophageal,and cervical cancer.Conclusions:The cancer spectrum of China is changing from a developing country to a developed country.Population aging and increase of unhealthy lifestyles would continue to increase the cancer burden of China.Therefore,the Chinese authorities should adjust the national cancer control program with reference to the practices of cancer control which have been well-established in the developed countries,and taking consideration of the diversity of cancer types by of different regions in China at the same time.展开更多
基金Beijing Municipal Science and Technol-ogy Commission(grant number Z211100002921013)Tongzhou Liang-gao Talents Project(grant number YH201920)+2 种基金Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research In-stitutes(grant number JYY2024-14)Beijing Municipal Public Wel-fare Development and Reform Pilot Project for Medical Research Insti-tutes(grant number JYY2023-15)We thank all participants and their families for supporting this study.
文摘Background: Small cell lung cancer (SCLC) is a highly aggressive disease characterized by early metastasis. Ane- uploid CD31- disseminated tumor cells (DTCs) and CD31+ disseminated tumor endothelial cells (DTECs) residing in the bone marrow are generally considered as the initiators of metastatic process. However, the clinical signifi- cance of DTCs and DTECs in SCLC remains poorly understood. The aim of this study is to investigate the clinical implications of diverse subtypes of highly heterogeneous DTCs and DTECs in SCLC patients. Methods: Subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) was applied to enrich and perform comprehensive morphologic, karyotypic, and phenotypic characterization of aneuploid DTCs and DTECs in 30 patients. Additionally, co-detection of circulating tumor cells (CTCs) and circulating tumor endothelial cells (CTECs) was conducted on 24 of the enrolled patients. Proof-of-concept of the whole exon sequencings (WES) on precisely selected different subtypes of CTCs or DTCs, longitudinally detected from a representative case with pathologically confirmed bone marrow metastasis, was validated to feasibly reveal genetic mutations in these cells. Results: DTCs, DTECs and their subtypes were readily detectable in SCLC patients. Comparative analysis re- vealed that the number of DTCs and DTECs was significantly higher than that of their corresponding CTCs and CTECs ( P < 0.001 for both). Positive detection of disseminated tumor microemboli (DTM) or disseminated tumor endothelial microemboli (DTEM) was associated with inferior survival outcomes ( P = 0.046 and P = 0.048). Pa- tients with EpCAM+ DTCs detectable displayed significantly lower disease control rate (DCR) (16.67% vs 73.33%, P = 0.019), reduced median progression-free survival (mPFS) and median overall survival (mOS) compared with those with EpCAM- DTCs ( P = 0.028 and P = 0.002, respectively). WES analysis indicated that post-treatment DTCs isolated from bone marrow at the time of disease progression shared more homologous somatic gene mu- tations with pre-treatment CTCs compared with post-treatment CTCs. Conclusions: Our findings suggest that bone marrow sampling and characterization of DTC subtypes provided a valuable tool for predicting treatment response and the prognosis in SCLC. Moreover, DTCs inherit a greater amount of homologous somatic information from pre-treatment CTCs, indicating their potential role in disease progression and treatment resistance.
文摘Cancer is the leading cause of death in China and depicting the cancer pattern of China would provide basic knowhows on how to tackle it more effectively.In this study we have reviewed several reports of cancer burden,including the Global cancer statistics 2018 and Cancer statistics in China,2015,along with the GLOBCAN 2018 online database,to investigate the differences of cancer patterns between China,the United States(USA)and the United Kingdom(UK).An estimated 4.3 million new cancer cases and 2.9 million new cancer deaths occurred in China in 2018.Compared to the USA and UK,China has lower cancer incidence but a 30%and 40%higher cancer mortality than the UK and USA,among which 36.4%of the cancer-related deaths were from the digestive tract cancers(stomach,liver,and esophagus cancer)and have relatively poorer prognoses.In comparison,the digestive cancer deaths only took up≤5%of the total cancer deaths in either USA or UK.Other reasons for the higher mortality in China may be the low rate of early-stage cancers at diagnosis and non-uniformed clinical cancer treatment strategies performed by different regions.China is undergoing the cancer transition stage where the cancer spectrum is changing from developing country to developed country,with a rapidly increase cancer burden of colorectal,prostate,female breast cancers in addition to a high occurrence of infection-related and digestive cancers.The incidence of westernized lifestyle-related cancers in China(i.e.colorectal cancer,prostate,bladder cancer)has risen but the incidence of the digestive cancers has decreased from 2000 to 2011.An estimated 40%of the risk factors can be attributed to environmental and lifestyle factors either in China or other developed countries.Tobacco smoking is the single most important carcinogenic risk factor in China,contributing to~24.5%of cancers in males.Chronic infection is another important preventable cancer contributor which is responsible for~17%of cancers.Comprehensive prevention and control strategies in China should include effective tobacco-control policy,recommendations for healthier lifestyles,along with enlarg-ing the coverage of effective screening,educating,and vaccination programs to better sensitize greater awareness control to the general public.
文摘Background:Cancer is one of the leading causes of death and a main economic burden in China.Investigating the differences in cancer patterns and control strategies between China and developed countries could provide reference for policy planning and contribute to improving cancer control measures.In this study,we reviewed the rates and trends of cancer incidence and mortality and disability-adjusted life year(DALY)burden in China,and compared them with those in the United States(US)and the United Kingdom(UK).Methods:Cancer incidence,mortality,and DALY data for China,US and UK were obtained fromtheGLOBOCAN2020 online database,Global Burden of Disease(GBD)2019 study,and Cancer Incidence in Five Continents plus database(CI5 plus).Trends of cancer incidence and mortality in China,US,and UK were analyzed using Joinpoint regression models to calculate annual percent changes(APCs)and identify the best-fitting joinpoints.Results:An estimated 4,568,754 newly diagnosed cancer cases and 3,002,899 cancer deaths occurred in China in 2020.Additionally,cancers resulted in 67,340,309 DALYs in China.Compared to the US and UK,China had lower cancer incidence but higher cancer mortality andDALY rates.Furthermore,the cancer spectrum of China was changing,with a rapid increase incidence and burden of lung,breast,colorectal,and prostate cancer in addition to a high incidence and heavy burden of liver,stomach,esophageal,and cervical cancer.Conclusions:The cancer spectrum of China is changing from a developing country to a developed country.Population aging and increase of unhealthy lifestyles would continue to increase the cancer burden of China.Therefore,the Chinese authorities should adjust the national cancer control program with reference to the practices of cancer control which have been well-established in the developed countries,and taking consideration of the diversity of cancer types by of different regions in China at the same time.
