Single cell analysis unveils the commonality and heterogeneity between nasopharyngeal and oropharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) and oropharyngeal carcinoma (OPC) are subtypes of head and neck cancer with different treatment effects due to the heterogeneity of tumor microenvironments. This study was to investigate the distinctive tumor microenvironments of NPC and OPC. Analyzing single-cell data from 10 cases of each subtype, we reveal significant differences in cellular composition, with NPC microenvironment dominated by T/NK and B cells, and OPC characterized by prevalent epithelial cells and fibroblasts. Dynamic transitions of CD8 T cells are observed in both tumor types, involving shifts from naivety to cytotoxicity, proliferation, and eventual exhaustion/exhausted states. Additionally, Tregs exhibit heightened proliferative abilities in later developmental stages, concomitant with exhaustion. These highly proliferative T cells and Tregs manifest elevated glycolysis and lactate metabolism activities. Furthermore, we explore intercellular communication between glycolytic malignant epithelial cells and these proliferative T cells. These findings offer comprehensive insights into the heterogeneity of tumor microenvironments and provide a solid foundation for future therapeutic strategies and targeted interventions.

The clinical outcome of COVID-19 is strongly associated with microbiome dynamics in the upper respiratory tract.

OBJECTIVES: The respiratory tract is the portal of entry for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although a variety of respiratory pathogens other than SARS-CoV-2 have been associated with severe cases of COVID-19 disease, the dynamics of the upper respiratory microbiota during disease the course of disease, and how they impact disease manifestation, remain uncertain. METHODS: We collected 349 longitudinal upper respiratory samples from a cohort of 65 COVID-19 patients (cohort 1), 28 samples from 28 recovered COVID-19 patients (cohort 2), and 59 samples from 59 healthy controls (cohort 3). All COVID-19 patients originated from the earliest stage of the epidemic in Wuhan. Based on a modified clinical scale, the disease course was divided into five clinical disease phases (pseudotimes): "Healthy" (pseudotime 0), "Incremental" (pseudotime 1), "Critical" (pseudotime 2), "Complicated" (pseudotime 3), "Convalescent" (pseudotime 4), and "Long-term follow-up" (pseudotime 5). Using meta-transcriptomics, we investigated the features and dynamics of transcriptionally active microbes in the upper respiratory tract (URT) over the course of COVID-19 disease, as well as its association with disease progression and clinical outcomes. RESULTS: Our results revealed that the URT microbiome exhibits substantial heterogeneity during disease course. Two clusters of microbial communities characterized by low alpha diversity and enrichment for multiple pathogens or potential pathobionts (including Acinetobacter and Candida) were associated with disease progression and a worse clinical outcome. We also identified a series of microbial indicators that classified disease progression into more severe stages. Longitudinal analysis revealed that although the microbiome exhibited complex and changing patterns during COVID-19, a restoration of URT microbiomes from early dysbiosis toward more diverse status in later disease stages was observed in most patients. In addition, a group of potential pathobionts were strongly associated with the concentration of inflammatory indicators and mortality. CONCLUSION: This study revealed strong links between URT microbiome dynamics and disease progression and clinical outcomes in COVID-19, implying that the treatment of severe disease should consider the full spectrum of microbial pathogens present.

Computational exploration of the significance of COPS6 in cancer: Functional and clinical relevance across tumor types.

BACKGROUND: The COP9 signalosome subunit 6 (COPS6) has been implicated in cancer progression, while its precise role in most types of cancer remains elusive. AIM: To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases. METHODS: We used R software and online analysis databases to analyze the differential expression, prognosis, mutation and related functions of COPS6 in pan-cancer. RESULTS: Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types. Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases. Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation. Additionally, positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer. Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+ T cell infiltration in certain types of cancer. The correlation between COPS6 expression level and cancer-associated fibroblast infiltration exhibited heterogeneity, in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor, and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma. The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type. Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level. These genes were predominantly involved in processes, such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection. CONCLUSION: In conclusion, this study systematically explored the significance of COPS6 across different tumor types, providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

Identifying prognostic markers in spatially heterogeneous breast cancer microenvironment.

To gain deeper insights into the microenvironment of breast cancer, we utilized GeoMx Digital Spatial Profiling (DSP) technology to analyze transcripts from 107 regions of interest in 65 untreated breast cancer tissue samples. Our study revealed spatial heterogeneity in the expression of marker genes in tumor cell enriched, immune cell enriched, and normal epithelial areas. We evaluated a total of 55 prognostic markers in tumor cell enriched regions and 15 in immune cell enriched regions, identifying that tumor cell enriched regions had higher levels of follicular helper T cells, resting dendritic cells, and plasma cells than immune cell enriched regions, while the levels of resting CD4 memory in T cells and regulatory (Treg) T cells were lower. Additionally, we analyzed the heterogeneity of HLA gene families, immunological checkpoints, and metabolic genes in these areas. Through univariate Cox analysis, we identified 5 prognosis-related metabolic genes. Furthermore, we conducted immunostaining experiments, including EMILIN2, SURF4, and LYPLA1, to verify our findings. Our investigation into the spatial heterogeneity of the breast cancer tumor environment has led to the discovery of specific diagnostic and prognostic markers in breast cancer.

Functional crosstalk and regulation of natural killer cells in tumor microenvironment: Significance and potential therapeutic strategies.

Natural killer (NK) cells eliminate a large variety of tumor cells and abnormal cells. However, NK cells in the tumor microenvironment (TME) are often functionally depleted. A few subsets of NK cells even promote tumor growth. This study reviewed the biological properties of NK cells, the dynamic phenotypic changes of NK cells in the TME, and the communication between NK cells and other immune and nonimmune cells.

Exploration of spatial heterogeneity of tumor microenvironment in nasopharyngeal carcinoma via transcriptional digital spatial profiling.

The heterogeneity of nasopharyngeal carcinoma (NPC) leads to mixed clinical outcomes. We collected 92 regions of interest from 41 biopsies of patients with untreated NPC and obtained their transcripts using GeoMx Digital Spatial Profiling (DSP) technology. Spatial heterogeneity was determined by measuring the expression of marker genes in tumor cell-enriched (PanCK-expressing), immune cell-enriched (CD45-expressing), and normal epithelial (Endo) regions. We screened 16 prognostic markers in tumor cell-enriched regions and 4 prognostic markers in immune cell-enriched regions. The levels of CD8+ T follicular helper T cells, activated NK cells, and M0 macrophage contents were higher in tumor cell-enriched regions than in immune cell-enriched regions. Conversely, plasma cell and M2 macrophage levels were lower. The follicular helper T cells in tumor cell-enriched regions were negatively correlated with resting NK cells and positively correlated with activated NK cells. In immune cell-enriched regions, this relationship was reversed. We also explored the heterogeneity of HLA gene families, immune checkpoints, and metabolism-related genes in the three regions. In tumor cell-enriched regions, we obtained 19 prognosis-related metabolism genes via univariate cox analysis. We used multiplex immunofluorescence to verify the elevated expression of SLC8A1 and MDH1 in immune cell-enriched regions and tumor cell-enriched regions, respectively, both of which were associated with prognosis of NPC. In conclusion, we explored the spatial heterogeneity of the NPC tumor environment and found specific diagnostic and prognostic markers that can be used to differentiate tumor cell-enriched regions from immune cell-enriched regions in NPC.

Predictive value of circulating tumor cell counts during the treatment of cancer: interactions with the blood microenvironment.

OBJECTIVE: This study aimed to evaluate the prognostic value of circulating tumor cell (CTC) in tumor patients during treatment. METHODS: This study retrospectively analyzed clinical data obtained from 174 cancer patients during treatment. The relationship between the CTC counts and clinicopathological variables was analyzed. A ROC curve was applied to determine the optimal cut-off values and assess the predictive ability of the prognostic indicators. The overall survival (OS) for different prognostic factors was calculated using the Kaplan-Meier method, and the difference between the survival curves was then compared using the log-rank test. Cox regression model was used to investigate the effect of independent factors on patients' survival. RESULTS: The CTC-positive rate was positively correlated with the clinicopathological variables of TNM stage, tumor differentiation, serum CEA level, and ki-67%. In the differential analysis of hematological microenvironment parameters in CTC-positive and CTC-negative samples, the complete blood count, blood biological chemistry, tumor markers (CEA, CA19-9, CA72-4), and lymphocyte subpopulation were statistically significant. The results of the ROC curve analysis indicated that the serum CEA level was the best diagnostic indicator to discriminate the CTC count in tumor patients. Additionally, the results of the univariate and multivariate analyses of OS in relation to clinical variables revealed that the CTC counts were an independent prognostic factor for unfavorable OS. CONCLUSION: The CTC counts in patients with tumors undergoing treatment were significantly correlated with hematological microenvironment parameters. The detection of CTCs may therefore be used as an indicator of tumor prognosis.

The third inactivated vaccine booster dramatically enhanced SARS-CoV-2 antibody responses and did not influence the profile of prothrombotic antibody.

The purpose of this study is to investigate the production of both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibodies and autoantibodies in serum following the third booster vaccination of the inactivated COVID-19 vaccine, and to study the effect of B cell subsets with CD27 and CD38 phenotypes in peripheral blood on antibody production. Routine blood indexes, SARS-CoV-2 antibodies, platelet factor 4 and seven antiphospholipid antibodies were detected both before and 2 months after vaccination in the medical staff of the Zhongnan Hospital of Wuhan University. Peripheral blood B cell subtypes were detected before vaccination. Following immunization, the positive rate of anti-N-S1 immunoglobulin (IgG) had increased from 24.8% to 91.3% and the average antibody concentration had increased by 11 times. The positive rate of neutralizing antibody had increased from 24.8% to 91.3%, the average antibody concentration had increased by 12 times, and the primary increased anti-S1 IgG subtype was that of IgG1. Peripheral blood CD27 + CD38+ B cells were positively correlated with antibody levels after vaccination and were a predictor of the antibody response. In addition, although some indicators showed slight absolute changes, the blood parameters and antiphospholipid antibodies of most volunteers were normal both before and after COVID-19 inactivated vaccine inoculation, and there was no statistical difference in abnormal rates either before or after inoculation. Antibodies in vivo were increased after vaccination with the inactivated vaccine, and IgG1 was the main subtype involved in response to the vaccine. Vaccination with the inactivated COVID-19 vaccine did not appear to affect thrombus-related autoantibodies.

The emergence of tumor-infiltrating lymphocytes in nasopharyngeal carcinoma: Predictive value and immunotherapy implications.

The clinical study of nasopharyngeal carcinoma (NPC) often reveals a large number of lymphocytes infiltrating the primary tumor site. As an important part of the tumor microenvironment, tumor-infiltrating lymphocytes (TILs) do not exist alone but as a complex multicellular population with high heterogeneity. TILs play an extremely significant role in the occurrence, development, invasion and metastasis of NPC. The latest research shows that they participate in tumorigenesis and treatment, and the composition, quantity, functional status and distribution of TILs subsets have good predictive value for the prognosis of NPC patients. TILs are an independent prognostic factor for TNM stage and significantly correlated with better prognosis. Additionally, adoptive immunotherapy using anti-tumor TILs has achieved good results in a variety of solid tumors including NPC. This review evaluates recent clinical and preclinical studies of NPC, summarizes the role of TILs in promoting and inhibiting tumor growth, evaluates the predictive value of TILs, and explores the potential benefits of TILs-based immunotherapy in the treatment of NPC.

Metabolic Reprogramming Induces Macrophage Polarization in the Tumor Microenvironment.

Macrophages are one of the most important cells in the innate immune system, they are converted into two distinct subtypes with completely different molecular phenotypes and functional features under different stimuli of the microenvironment: M1 macrophages induced by IFN-γ/lipopolysaccharides(LPS) and M2 macrophages induced by IL-4/IL-10/IL-13. Tumor-associated macrophages (TAMs) differentiate from macrophages through various factors in the tumor microenvironment (TME). TAMs have the phenotype and function of M2 macrophages and are capable of secreting multiple cytokines to promote tumor progression. Both tumor cells and macrophages can meet the energy needs for rapid cell growth and proliferation through metabolic reprogramming, so a comprehensive understanding of pro-tumor and antitumor metabolic switches in TAM is essential to understanding immune escape mechanisms. This paper focuses on the functions of relevant signaling pathways and cytokines during macrophage polarization and metabolic reprogramming, and briefly discusses the effects of different microenvironments and macrophage pathogenicity, in addition to describing the research progress of inhibitory drugs for certain metabolic and polarized signaling pathways.

Novel approach by natural language processing for COVID-19 knowledge discovery.

BACKGROUND: The impact of COVID-19 on public health has mandated an 'all hands on deck' scientific response. The current clinical study and basic research on COVID-19 are mainly based on existing publications or our knowledge of coronavirus. However, efficiently retrieval of accurate, relevant knowledge on COVID-19 can pose significant challenges for researchers. METHODS: To improve quality in accessing important literature findings, we developed a novel natural language processing (NLP) method to automatically recognize the associations among potential targeted host organ systems, associated clinical manifestations, and pathways. We further validated these associations through clinician experts' evaluations and prioritize candidate drug targets through bioinformatics network analysis. RESULTS: We found that the angiotensin-converting enzyme 2 (ACE2), a receptor that SARS-CoV-2 required for cell entry, is associated with cardiovascular and endocrine organ system and diseases. Furthermore, we found SARS-CoV-2 is associated with some important pathways such as IL-6, TNF-alpha, and IL-1 beta-induced dyslipidemia, which are related to inflammation, lipogenesis, and oxidative stress mechanisms, suggesting potential drug candidates. CONCLUSION: We prioritized the list of therapeutic targets involved in antiviral and immune modulating drugs for experimental validation, rendering it valuable during public health crises marked by stresses on clinical and research capacity. Our automatic intelligence pipeline also contributes to other novel and emerging disease management and treatments in the future.

Clinical Performance of Nanopore Targeted Sequencing for Diagnosing Infectious Diseases.

The gold standard for confirming bacterial infections is culture-positive, which has a long sample-to-result turnaround time and poor sensitivity for unculturable and fastidious pathogens; therefore, it is hard to guide early, targeted antimicrobial therapy and reduce overuse of broad-spectrum antibiotics. Nanopore targeted sequencing (NTS) is reported to be advantageous in detection speed and range over culture in prior published reports. However, investigation of the clinical performance of NTS is deficient at present. Thus, we assessed the feasibility of NTS for the first time with cohort and systematic comparisons with traditional culture assays and PCR followed by Sanger sequencing. This retrospective study was performed on 472 samples, including 6 specimen types from 436 patients, to evaluate the clinical performance of NTS designed for identifying the microbial composition of various infections. Of these samples, 86.7% were found to be NTS positive, which was significantly higher than culture-positive (26.7%). A total of 425 significant human opportunistic bacteria and fungi detected by NTS were selected to go through validation with PCR followed by Sanger sequencing. The average accuracy rate was 85.2% (maximum 100% created by Cryptococcus neoformans, the last one 66.7% provided by both Staphylococcus haemolyticus and Moraxella osloensis, minimum 0% produced by Burkholderia cepacia). The accuracy rate also varied with sample type; the highest accuracy rate was found in pleural and ascites fluid (95.8%) followed by bronchoalveolar lavage fluid (88.7%), urine (86.8%), and wound secretions (85.0%), while the lowest was present in cerebrospinal fluid (58.8%). NTS had a diagnostic sensitivity of 94.5% and specificity of 31.8%. The positive and negative predictive values of NTS were 79.9% and 66.7%, respectively. For diagnosis of infectious diseases, the sensitivity was greatly increased by 56.7% in NTS compared with culture (94.5% vs 37.8%). Therefore, NTS can accurately detect the causative pathogens in infectious samples, particularly in pleural and ascites fluid, bronchoalveolar lavage fluid, urine, and wound secretions, with a short turnaround time of 8-14 h, and might innovatively contribute to personalizing antibiotic treatments for individuals with standardized protocols in clinical practices. IMPORTANCE Nanopore targeted sequencing (NTS) is reported to be advantageous in detection speed and range over culture in prior published reports. Investigation of the clinical performance of NTS is deficient at present. In our study, cohort and systematic comparisons among three assays (culture, NTS, and Sanger sequencing) were analyzed retrospectively for the first time. We found that NTS undoubtedly has incomparable advantages in accurately detecting the causative pathogens in infectious samples, particularly in pleural and ascites fluid, bronchoalveolar lavage fluid, urine, and wound secretions, with a short turnaround time of 8-14 h. For sterile specimens like blood and cerebrospinal fluid (CSF), the NTS outcomes should be validated using other nucleic acid based detection technology. Overall, NTS might innovatively contribute to guiding early, targeted antimicrobial therapy with lower cost and reduce overuse of broad-spectrum antibiotics.

Genomic Analysis of the Unusual Staphylococcus aureus ST630 Isolates Harboring WTA Glycosyltransferase Genes tarM and tagN.

Staphylococcus aureus (S. aureus) can cause a broad spectrum of diseases ranging from skin infections to life-threatening diseases in both community and hospital settings. The surface-exposed wall teichoic acid (WTA) has a strong impact on host interaction, pathogenicity, horizontal gene transfer, and biofilm formation in S. aureus. The unusual S. aureus ST630 strains containing both ribitol-phosphate (RboP) WTA glycosyltransferase gene tarM and glycerol-phosphate (GroP) WTA glycosyltransferase gene tagN have been found recently. Native PAGE analysis showed that the WTA of tagN, tarM-encoding ST630 strains migrated slower than that of non-tagN-encoding ST630 strains, indicating the differences in WTA structure. Some mobile genetic elements (MGEs) such as the unique GroP-WTA biosynthetic gene cluster (SaGroWI), SCCmec element, and prophages that probably originated from the CoNS were identified in tagN, tarM-encoding ST630 strains. The SaGroWI element was first defined in S. aureus ST395 strain, which was refractory to exchange MGEs with typical RboP-WTA expressing S. aureus but could undergo horizontal gene transfer events with other species and genera via the specific bacteriophage Φ187. Overall, our data indicated that this rare ST630 was prone to acquire DNA from CoNS and might serve as a novel hub for the exchange of MGEs between CoNS and S. aureus. IMPORTANCE The structure of wall-anchored glycopolymers wall teichoic acid (WTA) produced by most Gram-positive bacteria is highly variable. While most dominant Staphylococcus aureus lineages produce poly-ribitol-phosphate (RboP) WTA, the tagN, tarM-encoding ST630 lineage probably has a poly-glycerol-phosphate (GroP) WTA backbone like coagulase-negative staphylococci (CoNS). There is growing evidence that staphylococcal horizontal gene transfer depends largely on transducing helper phages via WTA as the receptor. The structural difference of WTA greatly affects the transfer of mobile genetic elements among various bacteria. With the growing advances in sequencing and analysis technologies, genetic analysis has revolutionized research activities in the field of the important pathogen S. aureus. Here, we analyzed the molecular characteristics of ST630 and found an evolutionary link between ST630 and CoNS. Elucidating the genetic information of ST630 lineage will contribute to understanding the emergence and diversification of new pathogenic strains in S. aureus.

Prognosis and antibody profiles in survivors of critical illness from COVID-19: a prospective multicentre cohort study.

BACKGROUND: There is a need to assess the long-term outcomes of survivors of critical illness from COVID-19. METHODS: Ninety-two survivors of critical illness from COVID-19 from four hospitals in Hubei Province, China participated in this prospective cohort study. Multiple characteristics, including lung function (lung volumes, diffusing capacity for carbon monoxide, chest computed tomography scores, and walking capacity); immune status (SARS-CoV-2-neutralising antibody and all subtypes of immunoglobulin (Ig) G against SARS-CoV-2, immune cells in response to ex vivo antigen peptide stimuli, and lymphocyte count and its subtypes); liver, coagulation, and kidney functions; quality of life; cognitive function; and mental status, were assessed after 3, 6, and 12 months of follow-up. RESULTS: Amongst the 92 enrolled survivors, 72 (78%) patients required mechanical ventilation. At 12 months, the predicted percentage diffusing capacity of lung for carbon monoxide was 82% (inter-quartile range [IQR]: 76-97%) with a residual volume of 77 (64-88)%. Other lung function parameters and the 6-min walk test improved gradually over time and were almost back to normal by 12 months. The titres of IgG and neutralising antibody to COVID-19 remained high at 12 months compared with those of controls who were not infected with COVID-19, although IgG titres decreased significantly from 34.0 (IQR: 23.8-74.3) to 15.0 (5.8-24.3) AU ml-1 (P<0.001), whereas neutralising antibodies decreased from 29.99 (IQR: 19.43-53.93) AU ml-1 at 6 months to 19.75 (13.1-29.8) AU ml-1 (P<0.001) at 12 months. In general, liver, kidney, physical, and mental functions also improved over time. CONCLUSIONS: Survivors of critical illness from COVID-19 show some persistent long-term impairments in lung function. However, a majority of these tests were normal by 12 months. These patients still had detectable levels of neutralising antibodies against SARS-CoV-2 and all types of IgG at 12 months, but the levels had declined over this time period. CLINICAL TRIAL REGISTRATION: None.

Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is the most common subcategory of head and neck squamous cell carcinoma (HNSCC). This study focused on the roles of cuproptosis related genes and Jab1 in the tumor microenvironment of NPC and HNSCC. Methods: Differential expression analysis of Jab1 and cuproptosis related genes in tumor cell enriched region (PanCK-expressing) and immune cell enriched region (CD45-expressing) of NPC microenvironment were performed by packages of R software. Survival analysis was performed using the survival and survminer packages. Corrplot package was used for correlation analysis. ConsensusClusterPlus package was used for cluster clustering among different regions of NPC, and functional enrichment analysis was performed using GSVA, GSEABase, clusterProfiler, org.Hs.eg.db and enrichplot packages. The pRRophetic package was used to predict drug sensitivity in NPC and HNSCC. Results: Relationships exist between cuproptosis related genes and Jab1 in the NPC microenvironment. The expression of cuproptosis related genes and Jab1 differed between tumor cell enriched region and immune cell enriched region. AKT inhibitor VIII, Doxorubicin, Bleomycin and Etoposide showed higher sensitivity to tumor cell than immune cell. In the high Jab1 group, higher expression of ATP7A, DBT, DLD and LIAS were associated with better prognosis of HNSCC patients. In contrast, in the low Jab1 group, higher expression of these genes is associated with worse prognosis of HNSCC patients. Conclusions: Prognostic cuproptosis related genes and Jab1 provided a basis for targeted therapy and drug development.

Pan-cancer analyses of Jab1/COPS5 reveal oncogenic role and clinical outcome in human cancer.

Jab1/COPS5 is associated with the progression of some cancers, however, its role in most cancers is still unclear.This study systematically explored the action and clinical application value of Jab1/COPS5 in different tumors based on large clinical data. We first identified by differential and survival analysis that Jab1/COPS5 was highly expressed as a high-risk gene in most cancers and was closely related to prognostic survival of patients based on the TCGA, GEO and CPTAC databases. Mutation analysis suggested that missense mutations were the main mutation type of Jab1. TMB and MSI were positively correlated with Jab1/COPS5 in most tumors, and patients with Jab1/COPS5 mutations had a poorer prognosis in prostate adenocarcinoma. By immune infiltration analysis, Jab1/COPS5 expression was positively correlated with the infiltration of CD8+ T cells in thymoma and uveal melanoma, and Jab1/COPS5 expression in testicular germ cell tumors was negatively correlated with the infiltration of cancer-associated fibroblasts. Correlation and enrichment analysis suggested that ARMC1, TCEB1 and UBE2V2 were positively correlated with Jab1/COPS5 expression and involved in multiple biological effects. In summary, this study systematically investigated the role of Jab1/COPS5 in different tumors, providing a theoretical basis for Jab1/COPS5 as a new biomarker in unresearched cancers and paving the way for targeted therapy and drug development.

COVID-19 and Cancer: Discovery of Difference in Clinical Immune Indexes.

OBJECTIVE: This study explored the consistency and differences in the immune cells and cytokines between patients with COVID-19 or cancer. We further analyzed the correlations between the acute inflammation and cancer-related immune disorder. METHODS: This retrospective study involved 167 COVID-19 patients and 218 cancer patients. COVID-19 and cancer were each further divided into two subgroups. Quantitative and qualitative variables were measured by one-way ANOVA and chi-square test, respectively. Herein, we carried out a correlation analysis between immune cells and cytokines and used receiver operating characteristic (ROC) curves to discover the optimal diagnostic index. RESULTS: COVID-19 and cancers were associated with lymphopenia and high levels of monocytes, neutrophils, IL-6, and IL-10. IL-2 was the optimal indicator to differentiate the two diseases. Compared with respiratory cancer patients, COVID-19 patients had lower levels of IL-2 and higher levels of CD3+CD4+ T cells and CD19+ B cells. In the subgroup analysis, IL-6 was the optimal differential diagnostic parameter that had the ability to identify if COVID-19 patients would be severely affected, and severe COVID-19 patients had lower levels of lymphocyte subsets (CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+T cells, and CD19+ B cells) and CD16+CD56+ NK cells and higher level of neutrophils. There were significant differences in the levels of CD3+CD4+ T cells and CD19+ B cells between T1-2 and T3-4 stages as well as IL-2 and CD19+ B cells between N0-1 and N2-3 stages while no significant differences between the metastatic and nonmetastatic cancer patients. Additionally, there were higher correlations between IL-2 and IL-4, TNF-α and IL-2, TNF-α and IL-4, TNF-α and IFN-γ, and CD16+CD56+NK cells and various subsets of T cells in COVID-19 patients. There was a higher correlation between CD3+CD4+ T cells and CD19+ B cells in cancer patients. CONCLUSION: Inflammation associated with COVID-19 or cancer had effects on patients' outcomes. Accompanied by changes in immune cells and cytokines, there were consistencies, differences, and satisfactory correlations between patients with COVID-19 and those with cancers.

High Performance of SARS-Cov-2N Protein Antigen Chemiluminescence Immunoassay as Frontline Testing for Acute Phase COVID-19 Diagnosis: A Retrospective Cohort Study.

Objectives: COVID-19 emerged and rapidly spread throughout the world. Testing strategies focussing on patients with COVID-19 require assays that are high-throughput, low-risk of infection, and with small sample volumes. Antigen surveillance can be used to identify exposure to pathogens and measure acute infections. Methods: A total of 914 serum samples, collected from 309 currently infected COVID-19 patients, 48 recovered ones, and 410 non-COVID-19 patients, were used to measure N protein antigen levels by a chemilumineseent immunoassay. Diagnostic performances were analyzed in different periods after onset. Results: There was a high level of N protein antigen in COVID-19 patients (0.56 COI), comparing to the recovered patients (0.12 COI) and controls (0.19 COI). In receiver-operating characteristic curve analysis, the area under the curve of serum N protein antigen was 0.911 in the first week after onset. In this period, Sensitivity and specificity of serologic N protein antigen testing was 76.27 and 98.78%. Diagnosis performance of specific antibodies became better from the third week after onset. Subgroup analysis suggested that severe patients had higher levels of antigens than mild patients. Conclusions: High level of serum antigen suggested early infection and serious illness. Serum N protein antigen testing by chemiluminescence immunoassay is considered as a viable assay used to improve diagnostic sensitivity for current patients.