Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections

Background: The current COVID-19 pandemic has affected most severely people with old age, or with comorbidities like hypertension, diabetes mellitus, and cancer. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential.Method: We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors (DPP4, ANPEP, ENPEP, TMPRSS2) in human normal and cancer tissues of multiple organs including the brain, liver, kidney, heart, lung, skin, GI tract, pancreas, endocrine tissues, and the reproductive organs. RNA-Seq data from The Cancer Genome Atlas (TCGA) and GTeX databases were used for extensive profiling analysis of these receptors across 9,736 tumors and 8,587 normal tissues comparing coronavirus receptors. Protein expression from immunohistochemistry data was assessed from The Human Protein Atlas database including 144 samples, corresponding to 48 different normal human tissue types, and 432 tumor samples from 216 different cancer patients. The correlations between immune cell infiltration, chemokine, and cytokines were investigated via Tumor Immune Estimation Resource (TIMER) and TCGA.Result: We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus infection in renal carcinoma patients. The other receptors DPP4, ANPEP, and ENPEP may act as the compensatory receptor proteins to help ACE2. The receptors' expression levels were variable in different tumor stage, molecular, and immune subtypes of renal carcinoma. Intriguingly, in clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion.Conclusion: Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.

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Renal carcinoma is associated with increased risk of coronavirus infections

10.1101/2020.07.02.184663 ◽

2020 ◽

Author(s):

Satyendra C Tripathi ◽

Vishwajit Deshmukh ◽

Chad J. Creighton ◽

Ashlesh Patil

Keyword(s):

Protein Expression ◽

Renal Carcinoma ◽

Current Knowledge ◽

Tumor Stage ◽

Host Cells ◽

Normal Tissues ◽

Multiple Organs ◽

The People ◽

Increased Risk ◽

Gene And Protein Expression

AbstractThe current pandemic COVID-19 has affected most severely to the people with old age, or with comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, COPD, and cancers. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential. It is speculated that along with ACE2, other auxiliary proteins (DPP4, ANPEP, ENPEP, TMPRSS2) might facilitate the entry of coronaviruses in the host cells. We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. Here, we demonstrated an extensive RNA and protein expression profiling analysis of these receptors across solid tumors and normal tissues. We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus in renal carcinoma patients. The receptors’ expression levels were variable in different tumor stage, molecular and immune subtypes of renal carcinoma. In clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion. Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.

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Comprehensive Analysis of ESRRA in Endometrial Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821992083 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199208

Author(s):

Shufang Wang ◽

Xinlong Huo

Keyword(s):

Endometrial Cancer ◽

Protein Expression ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Operating Characteristics ◽

Protein Expression Level ◽

Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

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The tissue differentiation and cancer manifolds in gene and protein expression spaces

10.1101/2021.08.20.457160 ◽

2021 ◽

Author(s):

J Nieves ◽

A Gonzalez

Keyword(s):

Protein Expression ◽

Cancer Progression ◽

Tissue Differentiation ◽

The Cancer Genome Atlas ◽

Normal Tissues ◽

Gene And Protein Expression ◽

Human Protein Atlas ◽

Cancer Genome Atlas ◽

Tissue Of Origin ◽

Using Data

AbstractIt is well known that, for a particular tissue, the homeostatic and cancer attractors are well apart both in gene expression and in protein expression spaces. By using data for 15 tissues and the corresponding tumors from The Cancer Genome Atlas, and for 49 normal tissues and 20 tumors from The Human Protein Atlas, we show that the set of normal attractors are also well separated from the set of tumors. Roughly speaking, one may say that there is a cancer progression axis orthogonal to the normal tissue differentiation and cancer manifolds. This separation suggests that therapies targeting common genes, which define the cancer axis, may be effective, irrespective of the tissue of origin.

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Immunometabolic Status of COVID-19 Cancer Patients

Physiological Reviews ◽

10.1152/physrev.00018.2020 ◽

2020 ◽

Vol 100 (4) ◽

pp. 1839-1850

Author(s):

A. Sica ◽

M. P. Colombo ◽

A. Trama ◽

L. Horn ◽

M. C. Garassino ◽

...

Keyword(s):

Cancer Patients ◽

Cancer Progression ◽

Macrophage Activation ◽

Viral Infections ◽

Immune Cell ◽

Case Series ◽

The United States ◽

Alternative Activation ◽

Nad Metabolism ◽

Increased Risk

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.

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Enolase 1 Correlated With Cancer Progression and Immune-Infiltrating in Multiple Cancer Types: A Pan-Cancer Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.593706 ◽

2021 ◽

Vol 10 ◽

Author(s):

Wenhua Xu ◽

Wenna Yang ◽

Chunfeng Wu ◽

Xiaocong Ma ◽

Haoyu Li ◽

...

Keyword(s):

Cancer Progression ◽

Stress Protein ◽

Enrichment Analysis ◽

Tumor Stage ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Multiple Cancer ◽

Clinical Prognosis ◽

Multiple Tumor ◽

Normal Tissues

Enolase 1 (ENO1) is an oxidative stress protein expressed in endothelial cells. This study aimed to investigate the correlation of ENO1 with prognosis, tumor stage, and levels of tumor-infiltrating immune cells in multiple cancers. ENO1 expression and its influence on tumor stage and clinical prognosis were analyzed by UCSC Xena browser, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), and GTEx Portal. The ENO1 mutation analysis was performed by cBio Portal, and demonstrated ENO1 mutation (1.8%) did not impact on tumor prognosis. The relationship between ENO1 expression and tumor immunity was analyzed by Tumor Immune Estimation Resource (TIMER) and GEPIA. The potential functions of ENO1 in pathways were investigated by Gene Set Enrichment Analysis. ENO1 expression was significantly different in tumor and corresponding normal tissues. ENO1 expression in multiple tumor tissues correlated with prognosis and stage. ENO1 showed correlation with immune infiltrates including B cells, CD8+ and CD4+ T cells, macrophages, neutrophils, and dendritic cells, and tumor purity. ENO1 was proved to be involved in DNA replication, cell cycle, apoptosis, glycolysis process, and other processes. These findings indicate that ENO1 is a potential prognostic biomarker that correlates with cancer progression immune infiltration.

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The Effects of Simulated Microgravity on Macrophage Phenotype

Biomedicines ◽

10.3390/biomedicines9091205 ◽

2021 ◽

Vol 9 (9) ◽

pp. 1205

Author(s):

Christopher Ludtka ◽

Erika Moore ◽

Josephine B. Allen

Keyword(s):

Protein Expression ◽

Simulated Microgravity ◽

Prolonged Exposure ◽

Cell Function ◽

Immune Cell ◽

Expression Profiles ◽

Microgravity Environment ◽

M2 Macrophage ◽

Macrophage Function ◽

Gene And Protein Expression

The effects of spaceflight, including prolonged exposure to microgravity, can have significant effects on the immune system and human health. Altered immune cell function can lead to adverse health events, though precisely how and to what extent a microgravity environment impacts these cells remains uncertain. Macrophages, a key immune cell, effect the inflammatory response as well as tissue remodeling and repair. Specifically, macrophage function can be dictated by phenotype that can exist between spectrums of M0 macrophage: the classically activated, pro-inflammatory M1, and the alternatively activated, pro-healing M2 phenotypes. This work assesses the effects of simulated microgravity via clinorotation on M0, M1, and M2 macrophage phenotypes. We focus on phenotypic, inflammatory, and angiogenic gene and protein expression. Our results show that across all three phenotypes, microgravity results in a decrease in TNF-α expression and an increase in IL-12 and VEGF expression. IL-10 was also significantly increased in M1 and M2, but not M0 macrophages. The phenotypic cytokine expression profiles observed may be related to specific gravisensitive signal transduction pathways previously implicated in microgravity regulation of macrophage gene and protein expression. Our results highlight the far-reaching effects that simulated microgravity has on macrophage function and provides insight into macrophage phenotypic function in microgravity.

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Propping up the parents: An environmental scan of childcare programs available to cancer patients in North America.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e18805 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e18805-e18805

Author(s):

Katherine Preston ◽

Mackenzie MacDonald ◽

Meredith Elana Giuliani ◽

Barbara L. Melosky ◽

Bonnie Leung ◽

...

Keyword(s):

Cancer Patients ◽

Current Knowledge ◽

Grey Literature ◽

The United States ◽

Care Needs ◽

Cancer Treatments ◽

Environmental Scan ◽

Pediatric Hospitals ◽

Current State ◽

Increased Risk

e18805 Background: Approximately 20% of newly diagnosed cancer patients are between the ages of 20 and 54, and many of these patients are also the primary caregivers of children. Qualitative studies focusing on this demographic indicate that patients who are parents struggle to balance their own care needs with those of their children. Further, a lack of childcare support during cancer treatments can negatively impact compliance and increase existing psychological stress for patients. In the efforts to establish a child-minding program at a major Canadian cancer centre, we carried out an environmental scan to evaluate the current state of childcare support for cancer patients. Methods: Firstly, a literature scan was conducted in order to assess current knowledge about childcare and cancer patients, which included the use of search engines, directed internet searches, a review of oncology conference proceedings and websites of oncology associations. Literature was selected based on pre-determined criteria. Secondly, 12 representatives from major Canadian cancer centres (CCC) completed a questionnaire assessing current childcare strategies at their respective institutions. Finally, a broad scan of the grey literature was conducted by investigating 161 Canadian and American hospitals for on-site childcare services, using lay-accessible searching techniques (hand-searching hospital websites, phone and email correspondences). Results: The literature scan identified seventeen primary articles, which focused largely on exploring the role strain faced by patients who are also parents. A single study explored the instrumental challenges of being a parent with cancer, and formally assessed the childcare needs of these patients. The questionnaire results indicated that only two of the twelve investigated CCCs had established an approach to child-minding for patients. The grey literature scan identified twenty-six on-site, patient-accessible child-minding centres at hospitals in Canada and the US based on pre-determined inclusion criteria. Of these, 76.9% of centres were associated with pediatric hospitals, and 69.2% were located in the United States. Most centres (76.9%) were open for over 30 hours per week, and 88.5% of centres were free of charge to users. Conclusions: These findings generally indicate that a minority of Canadian and American hospitals and cancer centres have formal childcare services in place to support patients who are also parents. As cancer patients are at increased risk for financial toxicity, they may be particularly in need of this kind of instrumental support. This highlights the importance of carrying out a targeted needs assessment in order to fully elucidate the need for patient-accessible childcare services at CCCs.

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The Clinical Significance and Prognostic Value of HER2 Expression in Bladder Cancer: a Systematic Review and Meta-analysis

10.21203/rs.3.rs-135089/v1 ◽

2020 ◽

Author(s):

Kai Gan ◽

Yue Gao ◽

KuangZheng Liu ◽

Bin Xu ◽

Ming Chen

Keyword(s):

Bladder Cancer ◽

Clinical Significance ◽

Prognostic Value ◽

Meta Analysis ◽

Growth Factor Receptor ◽

Tumor Stage ◽

The Cancer Genome Atlas ◽

Her2 Expression ◽

Large Tumor ◽

Normal Tissues

Abstract Objective: Human Epidermal Growth Factor Receptor 2 (HER2) is highly expressed in a variety of tumors and associated with patients’ prognosis, but its role in bladder cancer remains unclear. We conducted this meta-analysis to explore the clinical significance and prognostic value of HER2 in bladder cancer and its potentiality as an immunotherapy target.Methods: PubMed was searched for studies published between January 1, 2000 and January 1, 2020. The odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (95%CIs) were used to investigate the relationship between HER2 and bladder cancer. UALCAN website was used to obtain TCGA (The cancer genome atlas) database.Results: Our study includes 14 articles, 1398 patients. HER2 expression was significantly higher in bladder cancer than in normal tissues. Our meta-analysis results did not reveal any effect of gender on the expression of HER2 levels in bladder cancer patients. However, HER2 expression in male patients was significantly higher than that in women according to TCGA databases. HER2 expression was also associated with carcinoma in situ, multifocal tumors, large tumor size, high tumor stage and grade, lymph node metastases, risk of recurrence and progression, low recurrence-free survival (RFS) rate. HER2 expression status had no effect on overall survival.Conclusions: Our meta-analysis showed that HER2 expression was related to pathological malignancy and poor prognosis in bladder cancer which indicated that it could be used as an effective biomarker and therapeutic target.

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Predicting STAT1 as a prognostic marker in patients with solid cancer

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920917558 ◽

2020 ◽

Vol 12 ◽

pp. 175883592091755

Author(s):

Jinguo Zhang ◽

Fanchen Wang ◽

Fangran Liu ◽

Guoxiong Xu

Keyword(s):

Ovarian Cancer ◽

Prognostic Value ◽

Renal Carcinoma ◽

The Cancer Genome Atlas ◽

Solid Cancer ◽

Lower Grade ◽

High Grade ◽

Large Tumor ◽

Normal Tissues ◽

Tumor Types

Background: Aberrant activities of signal transducer and activator of transcription 1 (STAT1) have been implicated in cancer development. However, the prognostic value of STAT1 remains unclear. This report identified the role of STAT1 in prognosis in patients with solid cancer through open literature and The Cancer Genome Atlas (TCGA) database. Methods: Published articles were obtained from PubMed, Web of Science, and Embase databases according to a search strategy up to October 2019. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted to assess the prognostic factors of patients. TCGA datasets were used to explore the prognostic value of STAT1 in various cancers. Results: A total of 15 studies incorporating 2839 patients with solid cancers were included. Pooled data showed that overexpressed STAT1 favored long overall survival (OS) (HR = 0.604, 95% CI = 0.431–0.846, p = 0.003) and disease-specific survival (DSS) (HR = 0.650, 95% CI = 0.512–0.825, p = 0.000). In subgroup analyses, highly expressed STAT1 was correlated with long OS of patients with high-grade serous ovarian cancer and oral squamous cell carcinoma. Data extracted from TCGA datasets unveiled that STAT1 expression was significantly higher in 12 cancers (e.g. bladder and breast) than their adjacent normal tissues. Again, highly expressed STAT1 favored long OS of patients with ovarian cancer as well as rectum adenocarcinoma, sarcoma, and skin cutaneous melanoma. However, in renal carcinoma, brain lower grade glioma, lung adenocarcinoma, and pancreatic cancer, highly expressed STAT1 was correlated with poor OS of patients. Particularly in renal carcinoma, increased STAT1 expression was associated with high grade, later stage, large tumor size, and lymph node and distant metastasis. Conclusion: STAT1 has been identified to have prognostic value in patients with solid cancer. Highly expressed STAT1 may predict prognosis in cancer patients based on their tumor types.

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Methylphenidate causes cytotoxicity on photoreceptor cells via autophagy

Human & Experimental Toxicology ◽

10.1177/0960327120940357 ◽

2020 ◽

Vol 40 (1) ◽

pp. 71-80

Author(s):

N Kong ◽

Y Bao ◽

H Zhao ◽

X Kang ◽

X Tai ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Expression ◽

Messenger Rna ◽

Cell Damage ◽

Photoreceptor Cells ◽

Cell Toxicity ◽

Hyperactivity Disorder ◽

Increased Risk ◽

Gene And Protein Expression ◽

Underlying Mechanisms

Methylphenidate (MPH) is used as the first-line treatment for attention-deficit hyperactivity disorder. However, there are concerns that this treatment may be associated with increased risk of retinal damage. This study was to investigate cytotoxicity of MPH on photoreceptor cells and explore its underlying mechanisms. MPH-caused cell toxicity was established in 661 W cells. Cytotoxicity was evaluated by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium-bromid and lactate dehydrogenase assays. Oxidative stress was measured by the markers: glutathione (GSH) reductase, catalase, and superoxide dismutase activities as well as GSH, reactive oxygen species, and malondialdehyde levels. Gene and protein expression was detected by real-time polymerase chain reaction (PCR) and western blot, respectively. Results showed that MPH decreased 661 W cell viability, increased caspase-3/9 activities, and induced oxidative stress. Furthermore, MPH treatment increased messenger RNA (mRNA) expression of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3B (LC3B) protein expression in 661 W cells, suggesting autophagy was induced. MPH treatment also upregulated p-JAK1/p-STAT1 protein expression. These data demonstrated that MPH could increase oxidative stress in photoreceptor cells to cause cell toxicity via autophagy, providing the scientific rationale for the photoreceptor cell damage caused by the MPH administration.

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