RESUMEN
The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.
Asunto(s)
Bronquios/citología , Expresión Génica , Pulmón/citología , Peptidil-Dipeptidasa A/genética , Serina Endopeptidasas/genética , Análisis de la Célula Individual , Adulto , Envejecimiento , Enzima Convertidora de Angiotensina 2 , Bronquios/metabolismo , COVID-19 , Células Cultivadas , Enfermedad Crónica/epidemiología , Infecciones por Coronavirus/genética , Células Epiteliales/metabolismo , Femenino , Perfilación de la Expresión Génica , Alemania , Células Caliciformes/metabolismo , Humanos , Pulmón/metabolismo , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/genética , Estándares de Referencia , Análisis de Secuencia de ARN , Caracteres Sexuales , Fumar , Bancos de TejidosRESUMEN
Opportunities for early career members to get involved in ERS activities in 2018 http://ow.ly/rmyd30hDBCN.
RESUMEN
A major part of non-small cell lung cancer (NSCLC) patients treated with mono- or multimodal concept develop therapy resistance. Despite the abundance of biomarkers investigated in the past, there is still a need for valid NSCLC biomarkers. Glycodelin, an immunosuppressive endometrial protein, has been shown to be also expressed in NSCLC. Here, we investigated its potential as a biomarker in metastatic and advanced stage NSCLC. Glycodelin gene and protein expression were measured in 28 therapy-naïve resected tumors as well as in corresponding brain (n = 16) and adrenal gland (n = 12) metastasis by qPCR and IHC. Moreover, we correlated glycodelin gene expression of cryoconserved therapy-naïve biopsies (n = 55) of advanced stage patients with glycodelin serum concentrations and patient survival. Using follow-up samples of the patients, we monitored glycodelin serum concentrations during therapy. Glycodelin expression correlated between primary tumor and distant metastases within the same patients. The gene expression of glycodelin in therapy-naïve biopsies also correlated with the serum concentrations of the patients (r = 0.60). Patients with elevated serum concentrations showed a tendency in lower overall survival (p = 0.088) and measuring of glycodelin indicated a progression of the disease earlier compared to clinical diagnostic. Taken together, we demonstrate that glycodelin is a promising prognostic and follow-up biomarker for metastatic and advanced NSCLC.
RESUMEN
The @ERSTalk ECM Committee present highlights from #ERSLDN16 for Early Career Members http://ow.ly/tRYH305Owmz.
RESUMEN
Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor with a short survival time arising from the mesothelial cells of the pleura. Soluble mesothelin-related peptide (SMRP), osteopontin or EFEMP1 (Fibulin-3) are well described biomarkers for malignant mesothelioma with moderate sensitivity and specificity. In this study, we characterized the expression of glycodelin, a marker for risk pregnancy, in MPM by RNA and protein analyses and investigated its potential as a MPM biomarker. We were able to detect glycodelin in the serum of MPM patients. Compared to benign lung diseases, the serum levels were significant increased. Patients with high glycodelin serum levels revealed a worse overall survival. The glycodelin serum levels correlated with the tumor response to treatment. A comparison of SMRP and glycodelin serum measurement in a large patient cohort demonstrated that the detection of both soluble factors can increase the reliable diagnostic of MPM. Glycodelin was highly expressed in MPM tumors. Analyses of a tissue micro array indicated that the immunomodulatory form glycodelin A was expressed in MPM and correlated with the survival of the patients. Altogether, glycodelin seems to be a new potential biomarker for the aggressive malignant pleural mesothelioma.