Identification of peroxiredoxin 6 as a potential lung-adenocarcinoma biomarker for predicting chemotherapy response by proteomic analysis.

ABSTRACT

The prognosis of lung cancer remains poor due to the limited biomarker selection for treating patients with optimal chemotherapy. The aim of this study is to discover and identify new biomarkers with the value of predicting chemotherapy responses in a lung adenocarcinoma (AD) specimen. In this study, six pairs of pre-treatment fresh primary lung AD-cancer tumors with varied chemotherapy responses were used to discover new biomarkers by two-dimensional difference gel electrophoresis (2D DIGE). Among the matched protein spots, 19 were up-regulated and 18 were down-regulated in chemo-sensitive tumors versus chemo-resistant tissues. These differentially expressed proteins could be divided into five classes redox regulation protein, the cytoskeletal protein, cell metabolism enzymes or proteins, apoptosis, signal transduction mediated molecules, and other functional proteins. Proteins of interest, including PRDX2, PRDX6, and Gelsolin, were differentially expressed in chemo-sensitive tumors versus chemo-resistant tissues and these observations were validated by immunohistochemistry in 92 formalin-fixed and paraffin-embedded (FFPE) specimens. Our results demonstrated that PRDX6 protein expression was closely related to tumor response (cc2 = 5.57, P < 0.05), whereas no relationship of PRDX2 and Gelsolin were obtained with tumor response (cc2 = 0.51 P > 0.05, cc2 = 0.41 P > 0.05). This tissue proteomics study provides evidence that PRDX6 may be regarded as a predictive biomarker for poor chemotherapy response, which can be helpful in guiding pretreatment protocols.