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Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics.

ABSTRACT: Chemotherapy is an important adjuvant therapy for epithelial ovarian cancer (EOC). The main cause of chemotherapy failure in EOC is paclitaxel resistance. The present study aimed to identify novel biomarkers to predict chemosensitivity to paclitaxel and improve our understanding of the molecular mechanisms underlying paclitaxel resistance in EOC. In the present study, the heterogeneity of EOC was evaluated by adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) in vitro. Fresh samples were collected from 54 EOC cases during cytoreductive surgery. Tumor cells were isolated, cultured, and tested for sensitivity to paclitaxel. Proteins that were differentially expressed between paclitaxel-resistant tissues and paclitaxel-sensitive tissues were identified via isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. Two upregulated proteins, plexin domain containing 2 (Plxdc2) and cytokeratin 7 (CK7), were selected to verify the iTRAQ method using western blot analysis in EOC tissues with different chemosensitivities (sensitive, weakly sensitive and resistant). There was notable heterogeneity of chemosensitivity in the EOC specimens. Highly to mildly-differentiated or early-stage (I/II) EOC specimens had decreased sensitivity to paclitaxel compared with specimens with low differentiation (P<0.05) or an advanced stage (III; P<0.05), respectively. A total of 496 significantly differentially expressed proteins, including 263 that were downregulated (P<0.05) and 233 that were upregulated (P<0.05) in paclitaxel-resistant tissues compared with paclitaxel-sensitive tissues, were identified using iTRAQ in combination with LC-MS/MS. The expression levels of two proteins associated with paclitaxel resistance, Plxdc2 and CK7, were further validated by western blotting, which revealed that they were upregulated in the paclitaxel-resistant tissues. The present study determined candidate proteins associated with paclitaxel resistance in EOC. Plxdc2 and CK7 may be potential makers for distinguishing patients with paclitaxel-resistant EOC from those with paclitaxel-sensitive EOC.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6004651 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics.

Wang Yuanjing Y Li Hongxia H

Oncology letters 20180427 6

Chemotherapy is an important adjuvant therapy for epithelial ovarian cancer (EOC). The main cause of chemotherapy failure in EOC is paclitaxel resistance. The present study aimed to identify novel biomarkers to predict chemosensitivity to paclitaxel and improve our understanding of the molecular mechanisms underlying paclitaxel resistance in EOC. In the present study, the heterogeneity of EOC was evaluated by adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) <i>in vitro</i>. Fresh sa ...[more]

PMID: 29928353

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Project description:Sugarcane can suffer severe yield losses when affected by leaf scald, a disease caused by Xanthomonas albilineans. This bacterial pathogen colonizes the vascular system of sugarcane, which can result in reduced plant growth and plant death. In order to better understand the molecular mechanisms involved in the resistance of sugarcane to leaf scald, a comparative proteomic study was performed with two sugarcane cultivars inoculated with X. albilineans: one resistant (LCP 85-384) and one susceptible (ROC20) to leaf scald. The iTRAQ (isobaric tags for relative and absolute quantification) approach at 0 and 48 h post-inoculation (hpi) was used to identify and annotate differentially expressed proteins (DEPs). A total of 4295 proteins were associated with 1099 gene ontology (GO) terms by GO analysis. Among those, 285 were DEPs during X. albilineans infection in cultivars LCP 85-384 and ROC20. One hundred seventy-two DEPs were identified in resistant cultivar LCP 85-384, and 113 of these proteins were upregulated and 59 were downregulated. One hundred ninety-two DEPs were found in susceptible cultivar ROC20 and half of these (92) were upregulated, whereas the other half corresponded to downregulated proteins. The significantly upregulated DEPs in LCP 85-384 were involved in metabolic pathways, the biosynthesis of secondary metabolites, and the phenylpropanoid biosynthesis pathway. Additionally, the expression of seven candidate genes related to photosynthesis and glycolytic pathways, plant innate immune system, glycosylation process, plant cytochrome P450, and non-specific lipid transfer protein was verified based on transcription levels in sugarcane during infection by X. albilineans. Our findings shed new light on the differential expression of proteins in sugarcane cultivars in response to infection by X. albilineans. The identification of these genes provides important information for sugarcane variety improvement programs using molecular breeding strategies.

Dataset Information

Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics.

Publications

Identification of proteins associated with paclitaxel resistance of epithelial ovarian cancer using iTRAQ-based proteomics.

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