Erythropoietin-Producing Hepatocellular A1 is an Independent Prognostic Factor for Gastric Cancer.
BACKGROUND
Erythropoietin-producing hepatocellular (Eph) receptors are the largest subfamily of receptor tyrosine kinases that have been investigated as a possible target for molecular targeted therapy of various cancers.


METHODS
Patients (n = 222) who underwent gastrectomy for primary gastric cancer were enrolled in this study. Tumor protein expression of EphA1 and EphB6 in surgically resected specimen was investigated using immunohistochemistry. The associations between expression of EphA1 and EphB6 and clinicopathological factors and prognosis were analyzed.


RESULTS
High expression of EphA1 was associated with undifferentiated histology (P = 0.002), depth of tumor (P < 0.001), lymph node metastasis (P = 0.001), venous invasion (P = 0.015), stage (P = 0.001), and remote metastasis or recurrence (P < 0.001). In univariate analysis, patients with high expression of EphA1 had significantly poorer overall survival and relapse-free survival compared with patients with low EphA1 expression. The expression level of EphB6 was not associated with any clinicopathological factors and patient survival. Multivariate analysis indicated that depth of tumor [hazard ratio (HR) 9.26, 95 % confidence interval (CI) 0.03-0.46, P = 0.003], lymph node metastasis (HR 9.26, 95 % CI 0.07-0.39, P < 0.001), and high expression of EphA1 (HR 1.86, 95 % CI 0.29-0.99, P = 0.048) are independent prognostic factors for relapse-free survival.


CONCLUSIONS
EphA1 is a possible target of molecular targeted therapy of gastric cancer.
Department of Surgical Oncology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan, mnaksrg2@tmd.ac.jp.
Masatoshi
M
Nakagawa
Mikito
M
Inokuchi
Yoko
Y
Takagi
Keiji
K
Kato
Hirofumi
H
Sugita
Sho
S
Otsuki
Kazuyuki
K
Kojima
Hiroyuki
H
Uetake
Kenichi
K
Sugihara
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D008297:Male; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D036082:Receptor, EphA1 / Q000235:genetics / Q000378:metabolism*; D036081:Receptors, Eph Family; D013274:Stomach Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015996:Survival Rate
D014408:Biomarkers, Tumor; C106797:EPHB6 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036082:Receptor, EphA1; D036081:Receptors, Eph Family