Pfetin as a prognostic biomarker of gastrointestinal stromal tumors revealed by proteomics.
OBJECTIVE
We aimed to develop prognostic biomarkers for gastrointestinal stromal tumors (GIST) using a proteomic approach.


METHODS
We examined the proteomic profile of GISTs using two-dimensional difference gel electrophoresis. The prognostic performance of biomarker candidates was examined using a large-scale sample set and specific antibodies.


RESULTS
We identified 43 protein spots whose intensity was statistically different between GISTs with good and poor prognosis. Mass spectrometric protein identification showed that the 43 spots corresponded to 25 distinct gene products. Eight of the 43 spots derived from pfetin, a potassium channel protein, and four of the eight pfetin spots had a high discriminative power between the two groups. Western blotting and real-time PCR showed that pfetin expression and tumor metastasis were inversely related. The prognostic performance of pfetin was also examined by immunohistochemistry on 210 GIST cases. The 5-year metastasis-free survival rate was 93.9% and 36.2% for patients with pfetin-positive and pfetin-negative tumors, respectively (P < 0.0001). Univariate and multivariate analyses revealed that pfetin expression was a powerful prognostic factor among the clinicopathologic variables examined, including risk classification and c-kit- or platelet-derived growth factor receptor A mutation status.


CONCLUSIONS
These results establish pfetin as a powerful prognostic marker for GISTs and may provide novel therapeutic strategies to prevent metastasis of GIST.
Suehara
Yoshiyuki
Y
Proteome Bioinformatics Project, National Cancer Center Research Institute, Tokyo, Japan.
Kondo
Tadashi
T
Seki
Kunihiko
K
Shibata
Tatsuhiro
T
Fujii
Kiyonaga
K
Gotoh
Masahiro
M
Hasegawa
Tadashi
T
Shimada
Yasuhiro
Y
Sasako
Mitsuru
M
Shimoda
Tadakazu
T
Kurosawa
Hisashi
H
Beppu
Yasuo
Y
Kawai
Akira
A
Hirohashi
Setsuo
S
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C493175:KCTD12 protein, human; D011506:Proteins