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The prognostic impact of RAP2A expression in patients with early and locoregionally advanced nasopharyngeal carcinoma in an endemic area.

ABSTRACT: BACKGROUND:By data mining from published transcriptomic databases, we identified RAP2A as a significantly upregulated gene in nasopharyngeal carcinoma (NPC) tissues. RAP2A, a member of the RAS oncogene family, is involved in the process of GTP binding and GTPase activity. The aim of this study was to evaluate the expression of RAP2A and its prognostic impact in patients with early and locoregionally advanced NPC. METHODS:RAP2A immunohistochemistry was performed for 124 NPC patients who were receiving standard treatment and had no initial distal metastasis. We also performed Western blotting to evaluate the endogenous protein expression of RAP2A in NPC cells and non-neoplastic mucosal cells. The result of RAP2A expression was further correlated with clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS). RESULTS:High expression of RAP2A was significantly associated with advanced primary tumor status (P = 0.024) and advanced TNM stage (P = 0.006). In univariate analysis, high expression of RAP2A served as a significant prognostic factor for inferior DSS (P < 0.0001), DMeFS (P < 0.0001), and LRFS (P < 0.0001). In multivariate analysis, RAP2A overexpression still independently predicted worse DSS (hazard ratio [HR] = 2.976, P < 0.001), DMeFS (HR = 4.233, P < 0.001), and LRFS (HR = 4.156, P < 0.001). Moreover, Both HONE1 and TW01 NPC cells, but not non-neoplastic DOK cells demonstrated significantly increased RAP2A expression. CONCLUSION:Overexpression of RAP2A is associated with advanced disease status and may therefore be an important prognosticator for poor outcomes in NPC, as well as a potential therapeutic target to aid in developing effective treatment modalities.

SUBMITTER: Lee YE

PROVIDER: S-EPMC4494142 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The prognostic impact of RAP2A expression in patients with early and locoregionally advanced nasopharyngeal carcinoma in an endemic area.

Lee Ying-En YE He Hong-Lin HL Chen Tzu-Ju TJ Lee Sung-Wei SW Chang I-Wei IW Hsing Chung-Hsi CH Li Chien-Feng CF

American journal of translational research 20150515 5

<h4>Background</h4>By data mining from published transcriptomic databases, we identified RAP2A as a significantly upregulated gene in nasopharyngeal carcinoma (NPC) tissues. RAP2A, a member of the RAS oncogene family, is involved in the process of GTP binding and GTPase activity. The aim of this study was to evaluate the expression of RAP2A and its prognostic impact in patients with early and locoregionally advanced NPC.<h4>Methods</h4>RAP2A immunohistochemistry was performed for 124 NPC patient ...[more]

PMID: 26175852

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Project description:BackgroundInduction chemotherapy (IC) can alleviate locoregionally advanced nasopharyngeal carcinoma (LA-NPC), but effectiveness differs between patients, toxicity is problematic, and effective blood-based IC efficacy predictors are lacking. Here, we aimed to identify biomarkers for early identification of IC beneficiaries.MethodsSixty-four pairs of matched plasma samples collected before and after IC from LA-NPC patients including 34 responders and 30 non-responders, as well as 50 plasma samples of healthy individuals, were tested using data-independent acquisition mass spectrometry. The proteins associated with clinical traits or IC benefits were investigated by weighted gene co-expression network analysis (WGCNA) and soft cluster analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional annotations were performed to determine the potential function of the identified proteins. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of candidate biomarkers in predicting IC beneficiaries.ResultsCompared with healthy individuals, 1027 differentially expressed proteins (DEPs) were found in the plasma of LA-NPC patients. Based on feedback from IC outcomes, 463 DEPs were identified in the pre-IC plasma between responders and non-responders. A total of 1212 DEPs represented the proteomic changes before and after IC in responders, while 276 DEPs were identified in post-IC plasma between responders and non-responders. WGCNA identified nine protein co-expression modules correlated with clinical traits. Soft cluster analysis identified four IC benefits-related protein clusters. Functional enrichment analysis showed that these proteins may play a role in IC via immunity, complement, coagulation, glycosaminoglycan and serine. Four proteins differentially expressed in all group comparisons, paraoxonase/arylesterase 1 (PON1), insulin-like growth factor-binding protein 3 (IGFBP-3), rheumatoid factor D5 light chain (v-kappa-3) and RNA helicase (DDX55), were associated with clinical traits or IC benefits. A four-protein model accurately identified potential IC beneficiaries (AUC=0.95) while diagnosing LA-NPC (AUC=0.92), and the prediction performance was verified using the models to confirm the effective IC (AUC=0.97) and evaluate IC outcome (AUC=0.94).ConclusionThe plasma protein profiles among IC responders and non-responders were different. PON1, IGFBP3, v-kappa-3 and DDX55 could serve as potential biomarkers for early identification of IC beneficiaries for individualised treatment of LA-NPC.

Dataset Information

The prognostic impact of RAP2A expression in patients with early and locoregionally advanced nasopharyngeal carcinoma in an endemic area.

Publications

The prognostic impact of RAP2A expression in patients with early and locoregionally advanced nasopharyngeal carcinoma in an endemic area.

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