Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ...Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.展开更多
Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as ...Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as well as the immune,nervous and endocrine systems,to construct a self-sustainable tumor ecosystem.With increasing evidence for the systemic tumor-host interplay,we predict that a new era of cancer therapy targeting the ecosystemic vulnerability of human malignancies has come.Revolving around the tumor ecosystem scoped as different hierarchies of primary,regional,distal and systemic onco-spheres,we comprehensively review the tumor-host interaction among cancer cells and their local microenvironment,distant organ niches,immune,nervous and endocrine systems,highlighting material and energy flow with tumor ecological homeostasis as an internal driving force.We also substantiate the knowledge of visualizing,modelling and subtyping this dynamically intertwined networkwith recent technological advances,and discuss ecologically rational strategies formore effective cancer therapies.展开更多
Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammato...Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.展开更多
基金supported by the National Key R&D Program of China (No. 2021YFF1201003)the Key R&D Program of Guangdong Province, China (No. 2021B0101420006)+2 种基金the National Science Fund for Distinguished Young Scholars (No. 81925023 and 82071892)the National Natural Science Foundation of China (No. 81771912 and 82071892)the National Natural Science Foundation for Young Scientists of China (No. 81701782 and 81901910).
文摘Objective: This study aimed to establish a method to predict the overall survival(OS) of patients with stage Ⅰ-Ⅲ colorectal cancer(CRC) through coupling radiomics analysis of CT images with the measurement of tumor ecosystem diversification.Methods: We retrospectively identified 161 consecutive patients with stage Ⅰ-Ⅲ CRC who had underwent radical resection as a training cohort. A total of 248 patients were recruited for temporary independent validation as external validation cohort 1, with 103 patients from an external institute as the external validation cohort 2. CT image features to describe tumor spatial heterogeneity leveraging the measurement of diversification of tumor ecosystem, were extracted to build a marker, termed the EcoRad signature. Multivariate Cox regression was used to assess the EcoRad signature, with a prediction model constructed to demonstrate its incremental value to the traditional staging system for OS prediction.Results: The EcoRad signature was significantly associated with OS in the training cohort [hazard ratio(HR)=6.670;95% confidence interval(95% CI): 3.433-12.956;P<0.001), external validation cohort 1(HR=2.866;95% CI: 1.646-4.990;P<0.001) and external validation cohort 2(HR=3.342;95% CI: 1.289-8.663;P=0.002).Incorporating the EcoRad signature into the prediction model presented a higher prediction ability(P<0.001) with respect to the C-index(0.813, 95% CI: 0.804-0.822 in the training cohort;0.758, 95% CI: 0.751-0.765 in the external validation cohort 1;and 0.746, 95% CI: 0.722-0.770 in external validation cohort 2), compared with the reference model that only incorporated tumor, node, metastasis(TNM) system, as well as a better calibration,improved reclassification and superior clinical usefulness.Conclusions: This study establishes a method to measure the spatial heterogeneity of CRC through coupling radiomics analysis with measurement of diversification of the tumor ecosystem, and suggests that this approach could effectively predict OS and could be used as a supplement for risk stratification among stage Ⅰ-Ⅲ CRC patients.
基金Natural Science Foundation of China,Grant/Award Numbers:81621004,81930081Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021A1515010238China Postdoctoral Science Foundation,Grant/Award Numbers:2020M683106,2021T140763。
文摘Cancer cells can be conceived as“living organisms”interacting with cellular or non-cellular components in the host internal environment,not only the local tumor microenvironment but also the distant organ niches,as well as the immune,nervous and endocrine systems,to construct a self-sustainable tumor ecosystem.With increasing evidence for the systemic tumor-host interplay,we predict that a new era of cancer therapy targeting the ecosystemic vulnerability of human malignancies has come.Revolving around the tumor ecosystem scoped as different hierarchies of primary,regional,distal and systemic onco-spheres,we comprehensively review the tumor-host interaction among cancer cells and their local microenvironment,distant organ niches,immune,nervous and endocrine systems,highlighting material and energy flow with tumor ecological homeostasis as an internal driving force.We also substantiate the knowledge of visualizing,modelling and subtyping this dynamically intertwined networkwith recent technological advances,and discuss ecologically rational strategies formore effective cancer therapies.
基金supported by the High-Level Talent Introduction Funds from the First Hospital of Lanzhou University.
文摘Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs,which is mediated by cancer cachexia factors.Cancer cachexia factors,being the general name of inflammatory factors,circulating proteins,metabolites,and microRNA secreted by tumor or host cells,play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia.Cancer cachexia factors are also a potential target for the diagnosis and treatment.The pathogenesis of cachexia is unclear and no clear effective treatment is available.Thus,the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed.From the point of signal communication between organs mediated by cancer cachexia factors,finding a deeper understanding of the pathogenesis,diagnosis,and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment.This review begins with cancer cachexia factors released during the interaction between tumor and host cells,and provides a comprehensive summary of the pathogenesis,diagnosis,and treatment for cancer cachexia,along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors.This summary aims to deepen medical community’s understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.
