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Clinical relevance of cytoskeleton associated proteins for ovarian cancer
- Source :
- Journal of cancer research and clinical oncology. 144(11)
- Publication Year :
- 2018
-
Abstract
- Ovarian cancer has a high mortality rate and up to now no reliable molecular prognostic biomarkers have been established. During malignant progression, the cytoskeleton is strongly altered. Hence we analyzed if expression of certain cytoskeleton-associated proteins is correlated with clinical outcome of ovarian cancer patients. First, in silico analysis was performed using the cancer genome atlas (TCGA), the human expression atlas and Pubmed. Selected candidates were validated on 270 ovarian cancer patients by qRT-PCR and/or by western blotting. In silico analysis revealed that mRNAs of 214 cytoskeleton-associated proteins are detectable in ovarian cancer tissue. Among these, we selected 17 proteins that participate in cancer disease progression and cytoskeleton modulation: KIF14, KIF20A, KIF18A, ASPM, CEP55, DLGAP5, MAP9, EB1, KATNA1, DIAPH1, ANLN, SCIN, CCDC88A, FSCN1, GSN, VASP and CDC42. The first ten candidates interact with microtubules (MTs) and the others bind to actin filaments. Validation on clinical samples of ovarian cancer patients revealed that the expression levels of DIAPH1, EB1, KATNA1, KIF14 and KIF18A significantly correlated with clinical and histological parameters of ovarian cancer. High DIAPH1, EB1, KATNA1 and KIF14 protein levels were associated with increased overall survival (OAS) of ovarian cancer patients, while high DIAPH1 and EB1 protein levels were also associated with low differentiation of respective tumors (G2/3). Moreover, DIAPH1 was the only protein, whose expression significantly correlated with increased recurrence-free interval (RFI). Mainly the expression levels of the MT-associated proteins analyzed in this study, correlated with prolonged survival of ovarian cancer patients. From > 200 genes initially considered, 17 cytoskeletal proteins are involved in cancer progression according to the literature. Among these, four proteins significantly correlated with improved survival of ovarian cancer patients.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
In silico
macromolecular substances
Kaplan-Meier Estimate
Microtubules
ASPM
ANLN
03 medical and health sciences
0302 clinical medicine
Internal medicine
Cell Line, Tumor
medicine
Humans
Clinical significance
DIAPH1
Cytoskeleton
Ovarian Neoplasms
Hematology
business.industry
Gene Expression Profiling
General Medicine
medicine.disease
Prognosis
Blot
Gene Expression Regulation, Neoplastic
Actin Cytoskeleton
Cytoskeletal Proteins
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
Cancer research
Disease Progression
Female
business
Ovarian cancer
Protein Binding
Subjects
Details
- ISSN :
- 14321335
- Volume :
- 144
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Journal of cancer research and clinical oncology
- Accession number :
- edsair.doi.dedup.....14a511a595ed6d85fbd28e8b0106f0fd