Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Development of gene expression signatures for identifying novel factors that can overcome age-associated reprogramming barriers

ABSTRACT: To investigate the molecular features underlying senescence and rejuvenation during aged cell reprogramming and identify novel factors that can overcome age-associated barriers, we compared gene expression for reprogramming intermediates on D8 of tail-tip fibroblasts (TTFs) from young Wild Type (WT), old WT, and old p16 knockout (KO) mice. We collected TTFs from young WT, old WT, and old p16 KO mice and reprogrammed the cells by introducing four reprogramming factors, including Oct4, Sox2, Klf4, and c-Myc. Gene expression of reprogramming intermediates on D8 were compared. Two independent experiments were performed using different mice donors for each experiment.

ORGANISM(S): Mus musculus

SUBMITTER: Yee Sook Cho

PROVIDER: E-GEOD-79747 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:This is the proteomics part of the above project. Purpose: No blood-based biomarkers to detect OPSCC early before symptoms develop or before clinically visible. Diagnosis is solely based on histology of a visible tumour. Most OPSCC patients are diagnosed at an advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumours could be detected and treated at an earlier stage. Causes of OPSCC include smoking, alcohol misuse, and human papillomavirus (HPV). Tumours are separated according to WHO recommendations into HPV+ OPSCC and HPV- OPSCC using the proxy histological marker p16. We additionally separated our patients into these groups to determine whether the serum glycopeptides would differ between HPV+ and HPV- tumours, as these are distinct clinical entities. Patients and Methods: Pre-treatment sera from 74 patients with OPSCC (including 26 p16- tumours and 48 p16+ tumours) and 12 controls were used, collected between the years 2012 and 2015 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Samples were grouped as follows: early stage p16+ OPSCC (stage I only), early stage p16- OPSCC (stage I-II), p16+ (any stage), p16- (any stage), controls. In-parallel quantitative bulk serum proteomics and serum glycopeptidomics were performed. Results: We identified 78 bulk proteins in the serum, of which 33 significantly differed between early-stage p16- OPSCC and controls, 22 between early-stage p16+ OPSCC and controls, 1 between early-stage p16+ and early-stage p16- OPSCCs, and 30 between all p16+ and p16- OPSCCs. We identified glycopeptides from proteins including but not limited to alpha-1-antitrypsin, haptoglobin, and Immunoglobulin heavy constant alpha 1, and compared these with the protein expression levels in each comparison. Conclusions: We have identified novel serum glycopeptide biomarkers detect early-stage OPSCCs, to be evaluated further as a diagnostic panel to detect preclinical OPSCC in at-risk patients.

Project description:This is the glycopeptide part of the above project. Purpose: No blood-based biomarkers to detect OPSCC early before symptoms develop or before clinically visible. Diagnosis is solely based on histology of a visible tumour. Most OPSCC patients are diagnosed at an advanced stage, which leads to significant morbidity and poor survival. If high-risk patients were identified with blood-based biomarkers before clear clinical manifestations, tumours could be detected and treated at an earlier stage. Causes of OPSCC include smoking, alcohol misuse, and human papillomavirus (HPV). Tumours are separated according to WHO recommendations into HPV+ OPSCC and HPV- OPSCC using the proxy histological marker p16. We additionally separated our patients into these groups to determine whether the serum glycopeptides would differ between HPV+ and HPV- tumours, as these are distinct clinical entities. Patients and Methods: Pre-treatment sera from 74 patients with OPSCC (including 26 p16- tumours and 48 p16+ tumours) and 12 controls were used, collected between the years 2012 and 2015 at the Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland. Samples were grouped as follows: early stage p16+ OPSCC (stage I only), early stage p16- OPSCC (stage I-II), p16+ (any stage), p16- (any stage), controls. In-parallel quantitative bulk serum proteomics and serum glycopeptidomics were performed. Results: We identified 78 bulk proteins in the serum, of which 33 significantly differed between early-stage p16- OPSCC and controls, 22 between early-stage p16+ OPSCC and controls, 1 between early-stage p16+ and early-stage p16- OPSCCs, and 30 between all p16+ and p16- OPSCCs. We identified glycopeptides from proteins including but not limited to alpha-1-antitrypsin, haptoglobin, and Immunoglobulin heavy constant alpha 1, and compared these with the protein expression levels in each comparison. Conclusions: We have identified novel serum glycopeptide biomarkers detect early-stage OPSCCs, to be evaluated further as a diagnostic panel to detect preclinical OPSCC in at-risk patients.

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Development of gene expression signatures for identifying novel factors that can overcome age-associated reprogramming barriers

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