Identification and characterization of potential biomarkers by quantitative tissue proteomics of primary lung adenocarcinoma

Chiung Hung Hsu, Chia Wei Hsu, Chuen Hsueh, Chih Liang Wang, Yi Cheng Wu, Chih Ching Wu, Chin Ching Liu, Jau Song Yu, Yu Sun Chang, Chia Jung Yu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

64 Scopus citations

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. Both diagnostic and prognostic biomarkers are urgently needed to increase patient survival. In this study, we identified/quantified 1763 proteins from paired adenocarcinoma (ADC) tissues with different extents of lymph node (LN) involvement using an iTRAQ-based quantitative proteomic analysis. Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1.5-fold increase in expression in ADC tumors without LN metastasis compared with adjacent normal tissues. These six proteins were further verified using immunohistochemical staining and Western blot analyses. The protein levels of these six candidates were higher in tumor tissues compared with adjacent normal tissues. The ERO1L and NARS levels were positively associated with LN metastasis. Importantly, ERO1L overexpression in patients with early-stage ADC was positively correlated with poor survival, suggesting that ERO1L overexpression in primary sites of early-stage cancer tissues indicates a high risk for cancer micrometastasis. Moreover, we found that knockdown of either ERO1L or NARS reduced the viability and migration ability of ADC cells. Our results collectively provide a potential biomarker data set for ADC diagnosis/prognosis and reveal novel roles of ERO1L and NARS in ADC progression.

Original languageEnglish
Pages (from-to)2396-2410
Number of pages15
JournalMolecular and Cellular Proteomics
Volume15
Issue number7
DOIs
StatePublished - 07 2016

Bibliographical note

Publisher Copyright:
© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

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