Validation study on pfetin and ATP-dependent RNA helicase DDX39 as prognostic biomarkers in gastrointestinal stromal tumour.
OBJECTIVE
This study aimed to validate two prognostic biomarkers, pfetin and adenosine triphosphate-dependent RNA helicase DDX39 (DDX39), in gastrointestinal stromal tumour. Prognostic biomarkers have long been required for the optimal use of kinase inhibitors in gastrointestinal stromal tumour.


METHODS
The expression level of pfetin was immunohistochemically examined in 72 gastrointestinal stromal tumour cases, being correlated with the clinicopathological parameters. Meta-analysis of the prognostic value of pfetin was performed in a total of 371 cases. The prognostic utility of the combination of pfetin and DDX39 was examined in the 72 gastrointestinal stromal tumour cases.


RESULTS
Immunohistochemical study demonstrated the disease-free survival rate to be 94.7% for pfetin-positive patients and 20.0% for pfetin-negative patients among the 72 gastrointestinal stromal tumour cases (P < 0.0001). In the 371 cases, the disease-free survival rate was 93.8% for pfetin-positive patients and 40.6% for pfetin-negative patients (P < 0.0001). Both univariate and multivariate analyses revealed that pfetin expression was an independent prognostic factor (P< 0.0001). When evaluated in combination with pfetin and DDX39, the disease-free survival rates were 0.0% for the pfetin-negative and DDX39-strong patients.


CONCLUSIONS
These results established the clinical utility of pfetin as a novel prognostic biomarker for gastrointestinal stromal tumour. The combined use of pfetin and DDX39 appeared to have powerful prognostic value. These biomarkers will be useful in deciding whether to administer adjuvant therapy after surgery.
Division of Pharmacoproteomics, National Cancer Center Research Institute, Tokyo, Japan.
Daisuke
D
Kubota
Taketo
T
Okubo
Tsuyoshi
T
Saito
Yoshiyuki
Y
Suehara
Akihiko
A
Yoshida
Kazutaka
K
Kikuta
Hitoshi
H
Tsuda
Hitoshi
H
Katai
Yasuhiro
Y
Shimada
Kazuo
K
Kaneko
Akira
A
Kawai
Tadashi
T
Kondo
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism; D053487:DEAD-box RNA Helicases / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011506:Proteins / Q000032:analysis*
D014408:Biomarkers, Tumor; C493175:KCTD12 protein, human; D011506:Proteins; C498428:DDX39A protein, human; D053487:DEAD-box RNA Helicases