Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We conducted comparative proteomic analysis of osteosarcoma, with hopes of identifying the specific protein markers of osteosarcoma and improve the understanding of tumorigenesis and progression of osteosarcoma. Proteins extracted from osteosarcoma tissue and benign bone tumors, including osteoblastoma, chondroblastoma, and giant cell tumor of bone, were examined using two-dimensional gel electrophoresis followed by mass spectrometry analysis and database searches. We also validated the expression levels of interesting proteins by Western blotting assay and immunohistochemical staining. Intensity alterations of 30 spots were detected in osteosarcoma, and 18 of these spots were finally identified, including 12 up-regulated proteins and 6 down-regulated ones. The up-regulated proteins include VIM, TUBA1C, ZNF133, EZR, ACTG1, TF, and so on. The six down-regulated proteins include ADCY1, ATP5B, TUBB, RCN3, ACTB, and YWHAZ. Subsequent immunohistochemical staining and Western blotting assay for TUBA1C and ZNF133 in osteosarcoma samples confirmed the observation obtained by proteomic analysis. Our results suggest that these identified proteins may be potential biomarkers for osteosarcoma tumorigenesis and therapeutics. Aberrant expression of cytoskeletal- and microtubule-associated proteins in osteosarcoma may provide an advantage for tumor invasion and metastasis by affecting the stability of microtubule, which consequently influences the prognosis of patients.
 ...
PMID:Comparative proteomics analysis of human osteosarcomas and benign tumor of bone. 2036 24

Osteosarcoma (OS), a bone tumor, exhibit a complex karyotype. On the genomic level a highly variable degree of alterations in nearly all chromosomal regions and between individual tumors is observable. This hampers the identification of common drivers in OS biology. To identify the common molecular mechanisms involved in the maintenance of OS, we follow the hypothesis that all the copy number-associated differences between the patients are intercepted on the level of the functional modules. The implementation is based on a network approach utilizing copy number associated genes in OS, paired expression data and protein interaction data. The resulting functional modules of tightly connected genes were interpreted regarding their biological functions in OS and their potential prognostic significance. We identified an osteosarcoma network assembling well-known and lesser-known candidates. The derived network shows a significant connectivity and modularity suggesting that the genes affected by the heterogeneous genetic alterations share the same biological context. The network modules participate in several critical aspects of cancer biology like DNA damage response, cell growth, and cell motility which is in line with the hypothesis of specifically deregulated but functional modules in cancer. Further, we could deduce genes with possible prognostic significance in OS for further investigation (e.g. EZR, CDKN2A, MAP3K5). Several of those module genes were located on chromosome 6q. The given systems biological approach provides evidence that heterogeneity on the genomic and expression level is ordered by the biological system on the level of the functional modules. Different genomic aberrations are pointing to the same cellular network vicinity to form vital, but already neoplastically altered, functional modules maintaining OS. This observation, exemplarily now shown for OS, has been under discussion already for a longer time, but often in a hypothetical manner, and can here be exemplified for OS.
...
PMID:Genomic heterogeneity of osteosarcoma - shift from single candidates to functional modules. 2584 66