Molleví D G, Aytes A, Padullés L, Martínez-Iniesta M, Baixeras N, Salazar R, Ramos E, Figueras J, Capella G, Villanueva A
Translational Research Laboratory, Institut Català d'Oncologia-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain.
Br J Cancer. 2008 Nov 18;99(10):1718-25. doi: 10.1038/sj.bjc.6604747. Epub 2008 Oct 28.
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.
磷酸酶PRL-3与多种癌症相关，尤其在结直肠癌（CRC）转移中发挥作用。在本研究中，我们探索了PRL-3的两种同工型作为预测IIIB-C期CRC复发的生物标志物。在裸鼠体内异种移植的原发性人类结直肠癌肿瘤（n = 20）和肝转移瘤（n = 36）中研究了PRL-3的过表达情况，这些样本的特征是不存在人类非肿瘤细胞，结果显示PRL-3在转移瘤中高度表达（P = 0.001）。在27例配对的正常结肠黏膜/原发性肿瘤/肝转移瘤病例中，PRL-3在原发性肿瘤与正常黏膜之间（P = 0.001）以及肝转移瘤与原发性肿瘤之间（P = 0.045）均出现过表达。此外，我们对80例IIIB-C期CRC原发性肿瘤的研究结果表明，在二元逻辑回归的多变量分析中，高水平的PRL-3是转移的独立预测因子（P < 0.0001；OR：9.791），并且PRL-3表达与不良预后参数密切相关。此外，在单变量（P < 0.0001）和多变量Cox模型中，PRL-3表达与不良预后相关（风险比：3.322，95%，置信区间：1.405 - 7.852，P = 0.006）。总之，PRL-3是局部晚期CRS侵袭性的良好标志物，也是远处转移的有前景的预测因子。然而，为了预后目的，必须在更大的连续系列和辅助治疗环境中验证PRL-3表达的临界值。
