Nuclear translocation of glutathione transferase omega is a progression marker in Barrett's esophagus
ABSTRACT Barrett's esophagus (BE) represents a major risk factor for esophageal adenocarcinoma (AC). For this reason, patients with BE are subjected to a systematic endoscopic surveillance to detect initial evolution towards non-invasive neoplasia (NiN) and cancer, that eventually occurs only in a small fraction of BE patients. This study was aimed to investigate the possible role of glutathione-S-transferase-omega 1 (GSTO1), a recently discovered member of the glutathione-S-transferase family, as a progression marker in the Barrett's disease in order to improve the diagnosis of NiN in BE and to understand the mechanisms of the progression from BE to AC. We investigated the expression and subcellular localization of GSTO1 in biopsies from patients with BE and in human cancer cell lines subjected to heath shock treatment. A selective nuclear localisation of GSTO1 was found in 16/16 biopsies with low- or high-grade NiN, while it appeared in only 4/22 BE biopsies without signs of NiN (P<0.0001). Among biopsies of BE without NiN, diffuse (nuclear and cytoplasmic) staining was found in 5/22 cases, while selective cytoplasmic localisation was found in 13/22. The 6 cases with indefinite grade of NiN were equally divided between nuclear, cytoplasmic and diffuse staining (2 each, respectively). Experiments in vitro showed that in human HeLa cancer cells, GSTO1 translocates into the nucleus as a consequence of heath shock. These findings suggested that the nuclear translocation of glutathione-S-transferase-omega 1 could be involved in the stress response of human cells playing a role in the cancer progression of Barrett's esophagus. Its immunohistochemical detection could represent a useful tool in the grading of Barrett's disease.
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ABSTRACT: Esophageal squamous cell carcinoma (ESCC) is the main form of esophageal malignancy. The approach for early diagnosis of this malignancy is very limited. In the present study, we first evaluated glutathione S-transferase omega 1 (GSTO1), a protein related to metabolism, as a tumor-associated antigen in ESCC, and we also evaluated its autoantibody as a potential biomarker in early detection of ESCC. First, immunohistochemistry (IHC) analysis of GSTO1 protein expression in esophageal tissues showed that the percentage of positive staining of GSTO1 in ESCC tissues was 87.5 % while there was no positive staining in adjacent tissues or normal tissues, indicating that overexpression of GSTO1 is closely related to ESCC. Then, enzyme-linked immunosorbent assay (ELISA) showed that the frequency of detectable autoantibody against GSTO1 in patients' sera totals 44.8 %. In contrast, the frequency of detectable autoantibody was only 6.7 % in normal human sera (p < 0.01). To further evaluate our ELISA results, western blotting and immunofluorescence assay were also performed. The results were consistent with the data from ELISA. In conclusion, the current study has demonstrated that GSTO1 protein is overexpressed in ESCC and can induce a detectable autoantibody response, which may serve as a potential biomarker in the early detection of ESCC.Tumor Biology 08/2014; 35(11). DOI:10.1007/s13277-014-2394-y · 3.61 Impact Factor