Locally advanced adeno- and squamous cell carcinoma of the esophagous (EAC, ESCC) and oral squamous cell carcinoma (OSCC) result in worse prognosis upon late diagnosis. We aim to identify tumor indicating ncRNAs in serum exosomes of tumor patients for earlier non-invasive diagnosis to contribute to a better outcome.
Differential gene and protein expression comparing tumor and normal tissues identified diagnostic, response predictive and prognostic tumor markers. Transfer to liquid biopsies now seems practicable by exosomes, components of the novel communication system of living cells. In addition to protein expressing genes, non-coding (nc-) RNAs like lnc-, circ-, and mi-RNA have been recognized as regulatory active key components with high impact for cancer development. Exosomal cargo provides an imense potential for creation of diagnostic marker signatures for earlier diagnosis. We profiled exosomal miRNAs, identified 80 exosomal miRNAs differentially concentrated between 12 OSCC tumor patients and 8 healthy blood donors. miRNome analysis was performed by TaqMan miRNA arrays. Six miRNA candidates have been selected for verification by 25 OSCC patients and 22 healthy blood donors. miR-409-3p has been identified as potential diagnostic candidate, p=0.001, fold change 0.203.
As an essiential step to detect tumor-indicative differences in exosomal cargo with better sensitivity 1. we need membrane proteins on the surface of the microvesicles, discriminating tumor cell secreted „oncosomes“ from exosomes originating from normal cells, 2. we aim to separate tumor cell derived „oncosomes“ from normal cells secreted exosomes, present in large abundance in serum of tumor patients.
By whole genome gene expression arrays we detected highly overexpressed membrane proteins as diagnostic signature which will be now examined in „oncosomal“ membranes for transfer to liquid biopsies.
Ute Warnecke-Eberz, molecular- and microbiologist, obtained PhD at the Freie University of Berlin, Germany in 1990. As head of lab for antiinfectiva research at Bayer Pharmaceutical Research in Wuppertal, Germany, she develoved screening assays to find antibacterials inhibiting protein-DNA interaction. 1999 establishing the lab for molecular oncology of the General-, Visceral- and Cancer Surgery at University Hospital of Cologne, she started research on diagnostic, response predictive and prognostic tumor markers for esophageal, gastric, oral and lung cancer. Since 2017 Prof. at University Hospital of Cologne focussing on real-time quantification of gene expression, and transfer of tumor marker results to liquid biopsy format. Actually evaluating the diagnostic use of serum exosomes and exosomal non-coding RNAs.