title: Loss of EphB6 protein expression in human colorectal cancer correlates with poor prognosis.
abstract: Erythropoietin-producing hepatocyte (Eph) receptor family constitutes the largest family of tyrosine kinase receptors in the human genome. Loss of EphB6, a kinase-deficient receptor, correlated with a negative outcome in several carcinomas. This study aimed to investigate the expression of EphB6 protein and mRNA levels in colorectal cancers (CRCs) and possible correlations with clinicopathological variables and prognosis. To assess protein expression level, 124 CRCs and 57 colorectal adenomas samples were examined by immunostaining, the mRNA level of 43 paired CRC and the adjacent normal tissues were detected by using SYBR Green real-time PCR method. Decreased expression of EphB6 protein was found in CRC as compared with adenoma and normal tissues (χ(2) = 10.146, P = 0.001 and χ(2) = 45.333, P < 0.001, respectively). Low EphB6 mRNA expression was detected in 83.8% of cancers with negative or low EphB6 protein expression. The loss of EphB6 protein in CRC was positively associated with poorly differentiation (P < 0.001), lymph node metastasis (P = 0.006), Dukes stage (P = 0.002) and depth of invasion (P = 0.016). The patients with lymph node metastasis had a worse prognosis independently of gender, age, tumor site, stage and differentiation (RR = 0.404, CI 0.267-0.213, P < 0.001). Low levels of EphB6 protein expression are associated with a shorter mean duration of survival in colorectal cancer. Our results demonstrated that EphB6 may represent a novel, useful tissue biomarker for the prediction of survival rate in CRC.
authors.affiliation: Department of Pathology, Jinling Hospital, Southern Medical University, Nanjing, 210002, China.
authors.forename: Libo
authors.initials: L
authors.lastname: Peng
authors.forename: Pin
authors.initials: P
authors.lastname: Tu
authors.forename: Xuan
authors.initials: X
authors.lastname: Wang
authors.forename: Shanshan
authors.initials: S
authors.lastname: Shi
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhou
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D036081:Receptors, Eph Family; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C106797:EPHB6 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D036081:Receptors, Eph Family