title: Overexpression of RalBP1 in colorectal cancer is an independent predictor of poor survival and early tumor relapse.
abstract: The non-ABC transport protein RalBP1 has been shown to be overexpressed in various cancer cell lines and implicated in the process of metastasis formation, but its expression in tissue samples and prognostic significance has not been shown. In this study matched tumor-mucosa tissue samples from 78 CRC patients were investigated. The RalBP1 mRNA and protein levels were quantified by real-time quantitative PCR (qPCR) and ELISA. RalBP1 was found to be overexpressed in tumor at the mRNA level both overall (p = 0.027), and for stages I (p = 0.024), II (p = 0.038) and IV (p = 0.004). At the protein level, RalBP1 was only significantly overexpressed in stage IV patients (p = 0.018). Expression of RalBP1 mRNA and protein were inversely correlated (r = 0.4173; p = 0.0004). Multivariate Cox regression analysis including sex, age, stage, grade, and nodal status as covariates showed that overexpression of RalBP1 protein, but not mRNA, was an independent predictor of both decreased disease free survival (p = 0.016, RR = 6.892) and overall survival (p = 0.039, RR = 5.986). These results suggest that RalBP1 protein is an independent predictor of poor survival and early relapse for CRC patients. Owing to its multifunctional intermediary role in cell survival, chemotherapeutic resistance, and metastasis formation, RalBP1 represents a promising novel therapeutic target.
authors.affiliation: Department of Surgery, University of Illinois at Mount Sinai Hospital, Chicago, IL USA. nathan.mollberg@gmail.com
authors.forename: Nathan M
authors.initials: NM
authors.lastname: Mollberg
authors.forename: Gunnar
authors.initials: G
authors.lastname: Steinert
authors.forename: Maximillian
authors.initials: M
authors.lastname: Aigner
authors.forename: Alexander
authors.initials: A
authors.lastname: Hamm
authors.forename: Fang-Ju
authors.initials: FJ
authors.lastname: Lin
authors.forename: Heike
authors.initials: H
authors.lastname: Elbers
authors.forename: Christoph
authors.initials: C
authors.lastname: Reissfelder
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Markus W
authors.initials: MW
authors.lastname: Buchler
authors.forename: Moritz
authors.initials: M
authors.lastname: Koch
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence
chemical_list: D018528:ATP-Binding Cassette Transporters; D020690:GTPase-Activating Proteins; C095637:RALBP1 protein, human; D012333:RNA, Messenger