Novel prognostic biomarker, pfetin, in gastrointestinal stromal tumors: Proteomics study

Abstract

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Recently, a c-kit tyrosine kinase inhibitor, imatinib mesylate, was introduced for the treatment of GIST. Imatinib showed dramatic tumor suppressive effects in metastatic or inoperable cases, and adjuvant treatment with imatinib following surgical resection reduced the risk of recurrence. Although the imatinib treatment is obviously beneficial for GIST patients, GIST spans a wide spectrum from a curable disorder to a highly malignant disease leading to metastasis and death, and risk stratification of GIST patients for imatinib therapy is desirable. To address this issue, we aimed to develop a prognostic biomarker for GIST. We conducted a proteomic study using surgically resected primary tumor tissues from GIST patients who underwent surgery and showed variable prognoses. Quantitative comparison resulted in identification of proteins with differential expression among the GIST patient groups. One of the proteins, pfetin, originally discovered as a gene unique to fetal cochlea, was preferentially expressed in patients with a favorable prognosis. Preferential expression of pfetin in GISTs with a favorable prognosis was confirmed by western blotting and immunohistochemistry. Prognostic utility of pfetin was established by immunohistochemical studies in 486 patients from 6 hospitals. Pfetin expression will be beneficial for selection of GIST patients for adjuvant treatment with imatinib.