Background: Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 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.

BackgroundAbundant evidence shows that triple-negative breast cancer (TNBC) is heterogeneous, and many efforts have been devoted to identifying TNBC subtypes on the basis of genomic profiling. However, few studies have explored the classification of TNBC specifically based on immune signatures that may facilitate the optimal stratification of TNBC patients responsive to immunotherapy.MethodsUsing four publicly available TNBC genomics datasets, we classified TNBC on the basis of the immunogenomic profiling of 29 immune signatures. Unsupervised and supervised machine learning methods were used to perform the classification.ResultsWe identified three TNBC subtypes that we named Immunity High (Immunity_H), Immunity Medium (Immunity_M), and Immunity Low (Immunity_L) and demonstrated that this classification was reliable and predictable by analyzing multiple different datasets. Immunity_H was characterized by greater immune cell infiltration and anti-tumor immune activities, as well as better survival prognosis compared to the other subtypes. Besides the immune signatures, some cancer-associated pathways were hyperactivated in Immunity_H, including apoptosis, calcium signaling, MAPK signaling, PI3K–Akt signaling, and RAS signaling. In contrast, Immunity_L presented depressed immune signatures and increased activation of cell cycle, Hippo signaling, DNA replication, mismatch repair, cell adhesion molecule binding, spliceosome, adherens junction function, pyrimidine metabolism, glycosylphosphatidylinositol (GPI)-anchor biosynthesis, and RNA polymerase pathways. Furthermore, we identified a gene co-expression subnetwork centered around five transcription factor (TF) genes (CORO1A, STAT4, BCL11B, ZNF831, and EOMES) specifically significant in the Immunity_H subtype and a subnetwork centered around two TF genes (IRF8 and SPI1) characteristic of the Immunity_L subtype.ConclusionsThe identification of TNBC subtypes based on immune signatures has potential clinical implications for TNBC treatment.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-1002-1) contains supplementary material, which is available to authorized users.

The 2019 novel coronavirus (SARS-CoV-2) pandemic has caused a global health emergency. The outbreak of this virus has raised a number of questions: What is SARS-CoV-2? How transmissible is SARS-CoV-2? How severely affected are patients infected with SARS-CoV-2? What are the risk factors for viral infection? What are the differences between this novel coronavirus and other coronaviruses? To answer these questions, we performed a comparative study of four pathogenic viruses that primarily attack the respiratory system and may cause death, namely, SARS-CoV-2, severe acute respiratory syndrome (SARS-CoV), Middle East respiratory syndrome (MERS-CoV), and influenza A viruses (H1N1 and H3N2 strains). This comparative study provides a critical evaluation of the origin, genomic features, transmission, and pathogenicity of these viruses. Because the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 is ongoing, this evaluation may inform public health administrators and medical experts to aid in curbing the pandemic's progression.

Polo-like kinase 1 (PLK1) plays an important role in the initiation, maintenance, and completion of mitosis. Dysfunction of PLK1 may promote cancerous transformation and drive its progression. PLK1 overexpression has been found in a variety of human cancers and was associated with poor prognoses in cancers. Many studies have showed that inhibition of PLK1 could lead to death of cancer cells by interfering with multiple stages of mitosis. Thus, PLK1 is expected to be a potential target for cancer therapy. In this article, we examined PLK1’s structural characteristics, its regulatory roles in cell mitosis, PLK1 expression, and its association with survival prognoses of cancer patients in a wide variety of cancer types, PLK1 interaction networks, and PLK1 inhibitors under investigation. Finally, we discussed the key issues in the development of PLK1-targeted cancer therapy.

Triple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed an exhaustive analysis of immunogenic signatures in TNBC based on 2 large-scale breast cancer (BC) genomic data. We compared enrichment levels of 26 immune cell activities and pathways among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. We found that almost all analyzed immune activities and pathways had significantly higher enrichment levels in TNBC than non-TNBC. Elevated enrichment of these immune activities and pathways was likely to be associated with better survival prognosis in TNBC. This study demonstrated that TNBC likely exhibits the strongest immunogenicity among BC subtypes, and thus warrants the immunotherapeutic option for TNBC.

BackgroundTumor mutation burden (TMB) has been associated with cancer immunotherapeutic response and cancer prognosis. Although many explorations have revealed that high TMB may yield many neoantigens to incite antitumor immune response, a systematic exploration of the correlation between TMB and immune signatures in different cancer types is lacking.ResultsWe classified cancer into the lower-TMB subtype and the higher-TMB subtype for each of 32 cancer types based on their somatic mutation data from the Cancer Genome Atlas (TCGA), and compared the expression levels of immune-related genes and gene-sets between both subtypes of cancers in each cancer type. In some cancer types most of the immune signatures analyzed were upregulated in the lower-TMB subtype, while in some other cancer types the immune signatures were prone to be upregulated in the higher-TMB subtype. However, the regulatory T cells, immune cell infiltrate, tumor-infiltrating lymphocytes, and cytokine signatures tended to be upregulated in the lower-TMB subtype, and the cancer-testis antigen (CTA) and pro-inflammatory signatures were inclined to be upregulated in the higher-TMB subtype. Importantly, high TMB was associated with elevated expression of PD-L1 in diverse prevailing cancers. Furthermore, we found that higher TMB was associated with better survival prognosis in numerous cancer types while was associated with worse prognosis in a few cancer types.ConclusionsHigh TMB may inhibit immune cell infiltrations while promote CTAs expression and inflammatory response in cancer. In many common cancer types, higher TMB may respond favorably to anti-PD-1/PD-L1 immunotherapy. Our data implicate that higher-TMB patients could gain a more favorable prognosis in diverse cancer types if treated with immunotherapy, otherwise would have a poorer prognosis compared to lower-TMB patients.Electronic supplementary materialThe online version of this article (10.1186/s12865-018-0285-5) contains supplementary material, which is available to authorized users.

Background Prior studies showed that tumor glycolysis and tumor immune evasion are interdependent. However, a systematic investigation of the association between tumor glycolysis and tumor immunity in various cancers remains lacking. Methods Using the Cancer Genome Atlas (TCGA) datasets, we explored the association between glycolytic activity and immune signatures in 14 cancer types. We also explored the associations between glycolytic activity and tumor immunity associated genetic features, including PD-L1 expression, tumor mutation burden (TMB), and tumor aneuploidy. Moreover, we performed in vitro experiments to verify some findings from bioinformatics analysis. Furthermore, we explored the association between tumor glycolytic activity and immunotherapy response. Findings Glycolytic activity was likely correlated with active immune signatures in various cancers and highly glycolytic tumors presented an immune-stimulatory tumor microenvironment. Compared to TMB and aneuploidy, glycolytic activity was a stronger and more consistent predictor for immune signatures in diverse cancers. Both computational and experimental analyses showed that glycolysis could increase PD-L1 expression in tumor. Glycolytic activity had a strong correlation with apoptosis which was a strong positive predictor for immune signatures, suggesting that apoptosis could be an important medium connecting glycolytic activity with immune activity in cancer. Finally, highly glycolytic tumors exhibited a better immunotherapy response and a favorable survival in the immunotherapy setting. Interpretation Tumor glycolysis may increase tumor immunity in diverse cancers. Glycolytic activity enhances PD-L1 expression on tumor cells and thus promotes anti-PD-1/PD-L1 immunotherapy response. Thus, the tumor glycolytic activity could be a predictive biomarker for immunotherapy response in diverse cancers. Fund This work was supported by the (grant numbers 3150120001, 2632018YX01 to XW).

Cancer cells gain a growth advantage through the so-called Warburg effect by shifting glucose metabolism from oxidative phosphorylation to aerobic glycolysis. Hypoxia-inducible factor 1 (HIF-1) has been suggested to function in metabolic reprogramming; however, the underlying mechanism has not been fully elucidated. We found that the aberrant expression of wild-type isocitrate dehydrogenase 3α (IDH3α), a subunit of the IDH3 heterotetramer, decreased α-ketoglutarate levels and increased the stability and transactivation activity of HIF-1α in cancer cells. The silencing of IDH3α significantly delayed tumor growth by suppressing the HIF-1-mediated Warburg effect and angiogenesis. IDH3α expression was associated with the poor postoperative overall survival of lung and breast cancer patients. These results justify the exploitation of IDH3 as a novel target for the diagnosis and treatment of cancers.