title: PRL-3 is essentially overexpressed in primary colorectal tumours and associates with tumour aggressiveness.
abstract: Phosphatase PRL-3 has been involved in different types of cancer, especially in metastases from colorectal carcinoma (CRC). In this study, we explored both isoforms of PRL-3 as a biomarker to predict the recurrence of stage IIIB-C CRC. Overexpression of PRL-3 was investigated in primary human colorectal tumours (n=20) and hepatic metastases (n=36) xenografted in nude mice, samples characterised by absence of human non-tumoral cells, showing a high degree of expression in metastases (P=0.001). In 27 cases of matched normal colonic mucosa/primary tumour/hepatic metastases, PRL-3 overexpression occurs in primary tumours vs normal mucosa (P=0.001) and in hepatic metastases vs primary tumours (P=0.045). Besides, our results in a series of 80 stage IIIB-C CRC primary tumours showed that high levels of PRL-3 were an independent predictor of metastasis (P<0.0001; OR: 9.791) in multivariate analysis of a binary logistic regression and that PRL-3 expression tightly correlates with parameters of bad outcome. Moreover, PRL-3 expression associated with poor outcome in univariate (P<0.0001) and multivariate Cox models (hazard ratio: 3.322, 95%, confidence interval: 1.405-7.852, P=0.006). In conclusion, PRL-3 is a good marker of aggressiveness of locally advanced CRS and a promising predictor of distant metastases. Nevertheless, for prognosis purposes, it is imperative to validate the cutoff value of PRL-3 expression in a larger and consecutive series and adjuvant setting.
authors.affiliation: Translational Research Laboratory, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: D G
authors.initials: DG
authors.lastname: Molleví
authors.forename: A
authors.initials: A
authors.lastname: Aytes
authors.forename: L
authors.initials: L
authors.lastname: Padullés
authors.forename: M
authors.initials: M
authors.lastname: Martínez-Iniesta
authors.forename: N
authors.initials: N
authors.lastname: Baixeras
authors.forename: R
authors.initials: R
authors.lastname: Salazar
authors.forename: E
authors.initials: E
authors.lastname: Ramos
authors.forename: J
authors.initials: J
authors.lastname: Figueras
authors.forename: G
authors.initials: G
authors.lastname: Capella
authors.forename: A
authors.initials: A
authors.lastname: Villanueva
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism* / Q000556:secondary; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases