Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label‐free LC/MS‐based protein quantification method

Abstract

Platinum-based chemotherapy, such as cisplatin, is the primary treatment for ovarian cancer. However, drug resistance has become a major impediment to the successful treatment of ovarian cancer. To date, the molecular mechanisms of resistance to platinum-based chemotherapy remain unclear. In this study, we applied an LC/MS-based protein quantification method to examine the global protein expression of two pairs of ovarian cancer cell lines, A2780/A2780-CP (cisplatin-sensitive/cisplatin-resistant) and 2008/2008-C13*5.25 (cisplatin-sensitive/cisplatinresistant). We identified and quantified over 2000 proteins from these cell lines and 760 proteins showed significant expression changes with a false discovery rate of less than 5% between paired groups. Based on the results we obtained, we suggest several potential pathways that may be involved in cisplatin resistance in human ovarian cancer. This study provides not only a new proteomic platform for large-scale quantitative protein analysis, but also important information for discovery of potential biomarkers of cisplatin resistance in ovarian cancer. Furthermore, these results may be clinically relevant for diagnostics, prognostics, and therapeutic improvement for ovarian cancer treatment.

Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

“…Interestingly, APOA1 and PRDX2 have also been found lobe up-regulated in ovarian cyst fluid of patients diagnosed with advanced serous ovarian adenocarcinoma (43). Additionally, studies conducted in Taxol-and platinum-resistant ovarian cancer cell lines have reported CH60, ENOA, ANXA2, CATD, heterogeneous nuclear ribonucleoprotein K (HNRPK) and heterogeneous nuclear ribonucleoproteins A2/B1 (ROA2) to be up-regulated in resistant cells when compared to their sensitive counterparts (24,25,44). Annexins A1 and A2 have been described as major substrates for the tyrosine phosphorylation carried out by the epidermal growth factor receptor (EGFR) (45).…”

Proteomics analysis of regenerating amphibian limbs: changes during the onset of regeneration

“…Peptide concentration in each pool was determined by the Bradford protein assay. All procedures for quantification of proteins, assurance of quality of the results and statistical analysis were carried out according to the detailed steps outlined by Fitzpatrick et al (2007) and Monarch Life Sciences, LLC. Details of the Methods used in this publication are included as supplementary materials.…”

Proteomics, a new tool to monitor cancer therapy?

“…Using LC/MS-based protein quantifi cation in cis-platin-sensitive and -resistant ovarian cancer cell lines, 760 out of 2000 identifi ed proteins showed signifi cant changes when sensitive and resistant cell lines were compared [9]. Not all of these changes are expected to be causative, but responses to causative changes.…”