Discovery of serum biomarkers implicated in the onset and progression of serous ovarian cancer in a rat model using iTRAQ technique
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY
Authors: Huang, Yiping; Zhang, Xiaoyan; Jiang, Wei; Wang, Yisheng; Jin, Hong; Liu, Xiaohui; Xu, Congjian
Abstract
Objective: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and early tumor detection is the most promising approach for improving the EOC survival rate. The goal of this study was to identify the biomarkers underlying ovarian carcinogenesis. Study design: To mimic the onset and progression of human ovarian cancer, we established a rat model of ovarian neoplasm by implanting 7,12-dimethylbenz(a)anthracene (DMBA)-coated silk cloth strips onto the ovaries. Sera collected from rats bearing serous ovarian carcinoma (SOC) at baseline, 12 and 24 weeks after DMBA treatment and from controls were analyzed using iTRAQ combined with two-dimensional liquid chromatography and tandem mass spectrometry. The data were analyzed with ProteinPilot software for peptide matching, protein identification, and protein quantitation. Ingenuity pathway analysis software was used to identify the canonical pathways and biological interaction networks of differentially expressed proteins. Results: The cumulative ovarian tumor incidence rate reached 75% at 32 weeks after DMBA treatment. Out of all tumors, 94% were EOC, and 51% of the EOC cases were SOC. A total of 225 unique, non-redundant proteins were identified with 95% confidence. Twenty-seven differentially expressed proteins were significantly up- or down-regulated during the early or advanced carcinogenesis of SOC. Fifteen proteins were previously reported to be involved in ovarian cancer, and 12 proteins, including MMRN1, SERPINC1, TLN1, AHSG, PLC, APOA2, HPX, APOC1, APOC2, FERMT3, FETUB and HBB, were identified for the first time in our study. Conclusion: The discovery of these differentially expressed proteins provides valuable clues for understanding the molecular mechanism underlying the dynamic carcinogenic process of ovarian cancer. These proteins could be used as diagnostic biomarkers for early detection, disease monitoring and therapeutic targets. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
Identification and characterization of secreted factors that are upregulated during somatic cell reprogramming
FEBS LETTERS
Authors: Bansho, Yoshimi; Lee, Joonseong; Nishida, Eisuke; Nakajima-Koyama, May
Abstract
The process of cell reprogramming has been characterized considerably since the successful generation of induced pluripotent stem cells. However, the importance of cell-cell communications for cellular reprogramming remains largely unknown. Secreted factors, which are expressed and secreted during reprogramming, may influence the reprogramming efficiency. Here, we have identified Sostdc1, Glb1l2, Fetub, Dpp4, Gdf3, Trh, and Tdgf1 as prominently upregulated secreted factors during reprogramming. Our detailed analysis reveals that these seven factors may be categorized into four groups based on their expression patterns in relation to the reprogramming stages. Remarkably, knockdown of Sostdc1, which is the most prominently upregulated factor and which is expressed earlier than the other six factors, results in reduced reprogramming efficiency, suggesting its involvement in the reprogramming process.