scholarly journals TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients.

2020 ◽  
Author(s):  
Andrea Sacconi ◽  
Sara Donzelli ◽  
Claudio Pulito ◽  
Stefano Ferrero ◽  
Francesca Spinella ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Target Genes ◽  
Host Cells ◽  
Spike Protein ◽  
Independent Effect ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Hnscc Patient ◽  
Proof Of Principle

Abstract Background: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas.Methods: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC.Results: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation.Conclusions: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

scholarly journals TMPRSS2, a SARS-CoV-2 Internalization Protease is Downregulated in Head and Neck Cancer Patients.

2020 ◽  
Author(s):  
Andrea Sacconi ◽  
Sara Donzelli ◽  
Claudio Pulito ◽  
Stefano Ferrero ◽  
Aldo Morrone ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Target Genes ◽  
Host Cells ◽  
Spike Protein ◽  
Independent Effect ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Hnscc Patient ◽  
Proof Of Principle

Abstract Background: SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas.Methods: The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC.Results: TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation.Conclusions: Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

scholarly journals TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Andrea Sacconi ◽  
Sara Donzelli ◽  
Claudio Pulito ◽  
Stefano Ferrero ◽  
Francesca Spinella ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Target Genes ◽  
Host Cells ◽  
Spike Protein ◽  
Independent Effect ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Hnscc Patient ◽  
Proof Of Principle

Abstract Background SARS-coronavirus-2 enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. We aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity, pharynx, larynx and lung tissues as well as neoplastic tissues from the same areas. Methods The study has been conducted using the TCGA and the Regina Elena Institute databases and validated by experimental model in HNSCC cells. We also included data from one COVID19 patient who went under surgery for HNSCC. Results TMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues. It was more evident in women than in men, in TP53 mutated versus wild TP53 tumors, in HPV negative patients compared to HPV positive counterparts. Functionally, we modeled the multivariate effect of TP53, HPV, and other inherent variables on TMPRSS2. All variables had a statistically significant independent effect on TMPRSS2. In particular, in tumor tissues, HPV negative, TP53 mutated status and elevated TP53-dependent Myc-target genes were associated with low TMPRSS2 expression. The further analysis of both TCGA and our institutional HNSCC datasets identified a signature anti-correlated to TMPRSS2. As proof-of-principle we also validated the anti-correlation between microRNAs and TMPRSS2 expression in a SARS-CoV-2 positive HNSCC patient tissues Finally, we did not find TMPRSS2 promoter methylation. Conclusions Collectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

scholarly journals Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Fei Tian ◽  
Rui Li ◽  
Zhenzhu Chen ◽  
Yanting Shen ◽  
Jiafeng Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Target Genes ◽  
Expression Profiles ◽  
Major Type ◽  
Regulatory Pathways ◽  
Normal Tissues ◽  
Qrt Pcr ◽  
Diagnosis And Prognosis ◽  
Tumor Tissues

Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer.

scholarly journals Boron Neutron Capture Therapy: A Review of Clinical Applications

2021 ◽  
Vol 11 ◽  
Author(s):  
Timothy D. Malouff ◽  
Danushka S. Seneviratne ◽  
Daniel K. Ebner ◽  
William C. Stross ◽  
Mark R. Waddle ◽  
...  
Keyword(s):  
Alpha Particle ◽  
Boron Neutron Capture Therapy ◽  
Neutron Capture ◽  
Neutron Capture Therapy ◽  
Breast Cancers ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Boron Neutron Capture ◽  
Pediatric Cancers ◽  
Tumor Tissues

Boron neutron capture therapy (BNCT) is an emerging treatment modality aimed at improving the therapeutic ratio for traditionally difficult to treat tumors. BNCT utilizes boronated agents to preferentially deliver boron-10 to tumors, which, after undergoing irradiation with neutrons, yields litihium-7 and an alpha particle. The alpha particle has a short range, therefore preferentially affecting tumor tissues while sparing more distal normal tissues. To date, BNCT has been studied clinically in a variety of disease sites, including glioblastoma multiforme, meningioma, head and neck cancers, lung cancers, breast cancers, hepatocellular carcinoma, sarcomas, cutaneous malignancies, extramammary Paget’s disease, recurrent cancers, pediatric cancers, and metastatic disease. We aim to provide an up-to-date and comprehensive review of the studies of each of these disease sites, as well as a review on the challenges facing adoption of BNCT.

The Expression of Egfl7 in Human Normal Tissues and Epithelial Tumors

2013 ◽  
Vol 28 (1) ◽  
pp. 71-83 ◽  
Author(s):  
Chun Fan ◽  
Lian-Yue Yang ◽  
Fan Wu ◽  
Yi-Ming Tao ◽  
Lin-Sen Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Normal Adult ◽  
Human Tissues ◽  
Epithelial Tumor ◽  
Normal Tissues ◽  
Adult Human ◽  
Epithelial Tumors ◽  
Tumor Tissues

Background and aims To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors. Methods RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results. Results Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. Conclusions Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

scholarly journals Gene Expression Analysis of Human Papillomavirus-Associated Colorectal Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Qiancheng Qiu ◽  
Yazhen Li ◽  
Zhiqiang Fan ◽  
Fen Yao ◽  
Wenjun Shen ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Signaling Pathways ◽  
Differentially Expressed Genes ◽  
Target Genes ◽  
Hpv Infection ◽  
Differentially Expressed ◽  
Noncancerous Tissue ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Taqman Array

Purpose. Human papillomavirus (HPV) antigens had been found in colorectal cancer (CRC) tissue, but little evidence demonstrates the association of HPV with oncogene mutations in CRC. We aim to elucidate the mutated genes that link HPV infection and CRC carcinogenesis. Methods. Cancerous and adjacent noncancerous tissues were obtained from CRC patients. HPV antigen was measured by using the immunohistochemical (IHC) technique. The differentially expressed genes (DEGs) in HPV-positive and HPV-negative tumor tissues were measured by using TaqMan Array Plates. The target genes were validated with the qPCR method. Results. 15 (31.9%) cases of CRC patients were observed to be HPV positive, in which HPV antigen was expressed in most tumor tissues rather than in adjacent noncancerous tissues. With TaqMan Array Plates analyses, we found that 39 differentially expressed genes (DEGs) were upregulated, while 17 DEGs were downregulated in HPV-positive CRC tissues compared with HPV-negative tissues. Four DEGs (MMP-7, MYC, WNT-5A, and AXIN2) were upregulated in tumor vs. normal tissues, or adenoma vs. normal tissue in TCGA, which was overlapped with our data. In the confirmation test, MMP-7, MYC, WNT-5A, and AXIN2 were upregulated in cancerous tissue compared with adjacent noncancerous tissue. MYC, WNT-5A, and AXIN2 were shown to be upregulated in HPV-positive CRC tissues when compared to HPV-negative tissues. Conclusion. HPV-encoding genome may integrate into the tumor genomes that involved in multiple signaling pathways. Further genomic and proteomic investigation is necessary for obtaining a more comprehensive knowledge of signaling pathways associated with the CRC carcinogenesis.

scholarly journals Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Zhicheng Yao ◽  
Ruiyun Xu ◽  
Lin Yuan ◽  
Mingxing Xu ◽  
Haiyun Zhuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Opposite Effect ◽  
Target Genes ◽  
Circular Rnas ◽  
Rna Molecules ◽  
Normal Tissues ◽  
Tumor Tissues

AbstractCircular RNAs (circRNAs) have been increasingly demonstrated to function as novel promising therapeutic RNA molecules for diverse human diseases, including cancer. Although the important role of circRNAs has been well documented in HCC, the complex mechanisms of circRNAs in HCC need to be elucidated. Here, a novel circRNA circ_0001955 was identified from three GSE datasets (GSE7852, GSE94508, and GSE97322) as a differentially expressed circRNA between HCC and normal samples. We revealed that circ_0001955, TRAF6 and MAPK11 levels were increased, while miR-516a-5p levels were decreased in HCC tumor tissues compared to adjacent normal tissues. Knockdown of circ_0001955 repressed HCC tumor growth in vitro and in vivo, while overexpression of circ_0001955 exhibited the opposite effect. Circ_0001955 was identified as a sponge for miR-145-5p and miR-516a-5p, and TRAF6 and MAPK11 were demonstrated to be two target genes of miR-516a-5p. In conclusion, circ_0001955 facilitated HCC tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11 expression.

Decreased Expression of Decorin and p57(KIP2) Correlates with Poor Survival and Lymphatic Metastasis in Lung Cancer Patients

2011 ◽  
Vol 26 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Rong Biaoxue ◽  
Cai Xiguang ◽  
Liu Hua ◽  
Ma Hui ◽  
Yang Shuanying ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Lymphatic Metastasis ◽  
Expression Level ◽  
Normal Lung ◽  
Tgf Beta ◽  
Expression Levels ◽  
Lung Cancer Patients ◽  
Normal Tissues ◽  
Tumor Tissues

Purpose Decorin, p57(KIP2), and TGF-beta 1 have been investigated as prognostic factors because they appear to be associated with tumorigenesis; however, the effect of decorin and p57(KIP2) in lung cancer remains poorly understood. The purpose of this study was to examine the expression of decorin, p57(KIP2), and TGF-beta 1 in 64 lung cancer specimens and 36 normal lung specimens, and to analyze the relationships with respect to clinicopathological features and patient survival in lung cancer. Methods The expression levels of decorin, p57(KIP2), and TGF-beta 1 were examined by in situ hybridization and immunohistochemistry. Results Normal tissues exhibited a higher expression level of decorin than tumor tissues (P<0.05) and tumor tissues exhibited a higher expression level of TGF-beta 1 than normal tissues (P<0.05). The expression levels of p57(KIP2) and TGF-beta 1 were significantly associated with histological types of lung cancer (P<0.05), and the expression levels of decorin and p57(KIP2) were significantly associated with lymphatic invasion (P<0.05). Moreover, increased expression of decorin and p57(KIP2) correlated with increased survival (decorin, p=0.018; p57(KIP2), p=0.012). Conclusion Decreased expression levels of decorin and p57(KIP2) were associated with poor postsurgical survival time and lymphatic metastasis in lung cancer patients; moreover, low expression was an adverse prognostic factor.

scholarly journals TMPRSS2, a SARS-CoV-2 internalization protease is downregulated in head and neck cancer patients

2020 ◽  
Author(s):  
Andrea Sacconi ◽  
Sara Donzelli ◽  
Claudio Pulito ◽  
Stefano Ferrero ◽  
Aldo Morrone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Oral Cavity ◽  
Cancer Patients ◽  
Expression Data ◽  
Wild Type ◽  
Sars Coronavirus ◽  
Lung Cancers ◽  
Normal Tissues ◽  
Link Type ◽  
Molecular Modulation

AbstractObjectivesTwo of the main target tissues of SARS-coronavirus 2 are the oral cavity pharynx-larynx epithelium, the main virus entry site, and the lung epithelium. The virus enters host cells through binding of the Spike protein to ACE2 receptor and subsequent S priming by the TMPRSS2 protease. Herein we aim to assess differences in both ACE2 and TMPRSS2 expression in normal tissues from oral cavity-pharynx-larynx and lung tissues as well as neoplastic tissues from the same histological areas. The information provided in this study may contribute to better understanding of SARS-coronavirus 2 ability to interact with different biological systems and contributes to cumulative knowledge on potential mechanisms to inhibit its diffusion.Materials and MethodsThe study has been conducted using The Cancer Genome Atlas (TCGA) and the Regina Elena Institute (IRE) databases and validated by experimental model in HNSCC and Lung cancer cells. Data from one COVID19 positive patient who was operated on for HNSCC was also included. We have analyzed 478 tumor samples and 44 normal samples from TCGA HNSCC cohort for whom both miRNA and mRNA sequencing was available. The dataset included 391 HPV- and 85 HPV+ cases, with 331 P53 mutated and 147 P53 wild type cases respectively. 352 out of 478 samples were male and 126 female. In IRE cohort we analyzed 66 tumor samples with matched normal sample for miRNA profiling and 23 tumor\normal matched samples for mRNA profiling. 45 out of 66 tumors from IRE cohort were male and 21 female, 38 were P53 mutated and 27 wild type. Most patients (63 of 66) in IRE cohort were HPV negative. Normalized TCGA HNSCC gene expression and miRNA expression data were obtained from Broad Institute TCGA Genome Data Analysis Center (http://gdac.broadinstitute.org/). mRNA expression data from IRE cohort used in this study has been deposited to NCBI’s Gene Expression Omnibus and is accessible through GEO series accession number GSE107591. In order to inference about potential molecular modulation of TMPRSS2, we also included miRNAs expression for the 66 IRE cohort matched tumor and normal samples from Agilent platform. DNA methylation data for TCGA tumors were obtained from Wanderer (http://maplab.imppc.org/wanderer/). We used miRWalk and miRNet web tools for miRNA-target interaction prediction and pathway enrichment analysis. The correlation and regression analyses as well as the miRNA and gene modulation and the survival analysis were conducted using Matlab R2019.ResultsTMPRSS2 expression in HNSCC was significantly reduced compared to the normal tissues and had a prognostic value in HNSCC patients. Reduction of TMPRSS2 expression was more evident in women than in men, in TP53 mutated versus wild TP53 tumors as well as in HPV negative patients compared to HPV positive counterparts. Functionally, we assessed the multivariate effect on TMPRSS2 in a single regression model. We observed that all variables had an independent effect on TMPRSS2 in HNSCC patients with HPV negative, TP53 mutated status and with elevated TP53-dependent Myc-target genes associated with low TMPRSS2 expression. Investigation of the molecular modulation of TMPRSS2 in both HNSCC and lung cancers revealed that expression of microRNAs targeting TMPRSS2 anti-correlated in both TCGA and IRE HNSCC datasets, while there was not evidence of TMPRSS2 promoter methylation in both tumor cohorts. Interestingly, the anti-correlation between microRNAs and TMPRSS2 expression was corroborated by testing this association in a SARS-CoV-2 positive HNSCC patient.ConclusionsCollectively, these findings suggest that tumoral tissues, herein exemplified by HNSCC and lung cancers might be more resistant to SARS-CoV-2 infection due to reduced expression of TMPRSS2. The protective mechanism might occur, at least partially, through the aberrant activation of TMPRSS2 targeting microRNAs; thereby providing strong evidence on the role of non-coding RNA molecule in host viral infection. These observations may help to better assess the frailty of SARS-CoV-2 positive cancer patients.

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