Gastrointestinal(GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have...Gastrointestinal(GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have a limited therapeutic effect for advanced GI cancers. Recently, immunotherapy has shown promise in treating various refractory malignancies, including the GI cancers with mismatch repair deficiency(dMMR) or microsatellite instability(MSI). Thus,immunotherapy could be a promising treatment approach for GI cancers.Unfortunately, only a small proportion of GI cancer patients currently respond to immunotherapy. Therefore, it is important to discover predictive biomarkers for stratifying GI cancer patients response to immunotherapy. Certain genomic features, such as dMMR/MSI, tumor mutation burden(TMB), and tumor aneuploidy have been associated with tumor immunity and im-munotherapy response and may serve as predictive biomarkers for cancer immunotherapy. In this review, we examined the correlations between tumor immunity and three genomic features: dMMR/MSI, TMB, and tumor aneuploidy. We also explored their correlations using The Cancer Genome Atlas data and confirmed that the dMMR/MSI status, high TMB, and low tumor aneuploidy are associated with elevated tumor immunity in GI cancers. To improve the immunotherapeutic potential in GI cancers, more genetic or genomic features associated with tumor immune response need to be identified. Furthermore, it is worth exploring the combination of different immunotherapeutic methods and the combination of immunotherapy with other therapeutic approaches for cancer therapy.展开更多
Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SAR...Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this virus have markedly distinct disease severity.This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.展开更多
基金the China Pharmaceutical University,No:3150120001
文摘Gastrointestinal(GI) cancers prevail and account for an extremely high number of cancer deaths worldwide. The traditional treatment strategies, including surgery, chemotherapy, radiotherapy, and targeted therapy, have a limited therapeutic effect for advanced GI cancers. Recently, immunotherapy has shown promise in treating various refractory malignancies, including the GI cancers with mismatch repair deficiency(dMMR) or microsatellite instability(MSI). Thus,immunotherapy could be a promising treatment approach for GI cancers.Unfortunately, only a small proportion of GI cancer patients currently respond to immunotherapy. Therefore, it is important to discover predictive biomarkers for stratifying GI cancer patients response to immunotherapy. Certain genomic features, such as dMMR/MSI, tumor mutation burden(TMB), and tumor aneuploidy have been associated with tumor immunity and im-munotherapy response and may serve as predictive biomarkers for cancer immunotherapy. In this review, we examined the correlations between tumor immunity and three genomic features: dMMR/MSI, TMB, and tumor aneuploidy. We also explored their correlations using The Cancer Genome Atlas data and confirmed that the dMMR/MSI status, high TMB, and low tumor aneuploidy are associated with elevated tumor immunity in GI cancers. To improve the immunotherapeutic potential in GI cancers, more genetic or genomic features associated with tumor immune response need to be identified. Furthermore, it is worth exploring the combination of different immunotherapeutic methods and the combination of immunotherapy with other therapeutic approaches for cancer therapy.
基金This work was supported by the China Pharmaceutical University(grant number 3150120001 to XW)。
文摘Background:Since its discovery in December 2019,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has infected more than 2180000 people worldwide and has caused more than 150000 deaths as of April 16,2020.SARS-CoV-2,which is the virus causing coronavirus disease 2019(COVID-19),uses the angiotensin-converting enzyme 2(ACE2)as a cell receptor to invade human cells.Thus,ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection.This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger(ages≤49 years)and older(ages>49 years)persons using two-sided Student's t test.We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine,testis,kidneys,heart,thyroid,and adipose tissue,and were the lowest in the blood,spleen,bone marrow,brain,blood vessels,and muscle.ACE2 showed medium expression levels in the lungs,colon,liver,bladder,and adrenal gland.ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue.In the skin,digestive system,brain,and blood vessels,ACE2 expression levels were positively associated with immune signatures in both males and females.In the thyroid and lungs,ACE2 expression levels were positively and negatively associated with immune signatures in males and females,respectively,and in the lungs they had a positive and a negative correlation in the older and younger groups,respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes,ages,and races equally.The different host immune responses to SARS-CoV-2 infection may partially explain why males and females,young and old persons infected with this virus have markedly distinct disease severity.This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.
