Biglycan expression and clinical outcome in patients with pancreatic adenocarcinoma
Biglycan expression and clinical outcome in patients with pancreatic adenocarcinoma
复制标题
DOI：
10.1007/s13277-012-0520-2
复制
发表时间：
2013-02-01
期刊：
影响因子：
--
通讯作者：
Piga, Andrea
中科院分区：
文献类型：
--
作者：
Aprile, Giuseppe;Avellini, Claudio;Piga, Andrea
关于细胞外基质(ECM)蛋白在胰腺癌中的作用，已有相互矛盾的结果报道。临床前研究表明，细胞外基质中一种富含亮氨酸的蛋白质Biglycan(Proteoglycan-I，PG-I)过表达可能导致胰腺癌细胞生长停滞。本研究的目的是评估Biglycan在胰腺癌中的表达对预后的影响。我们还评估了MIB-1和COX-2的表达(作为生长和侵袭性的潜在标志)，以更好地表征肿瘤的生物学特性。检查经典的病理参数(分级、纤维增生、神经周围或血管侵犯)以及影响预后的分子决定因素。采用免疫组织化学和免疫荧光方法检测53例胰腺癌组织标本中MIB-1、COX-2和PG-I的表达，并由两位独立的病理学家复习。为了验证PG-I的表达，我们测试了来自美国国立卫生研究院、马萨诸塞州贝塞斯达的三种兔血清(LF104、LF112和LF121)。统计分析采用LOGRANK检验和COX模型。在53名患者中，40名患者患有III和IV期胰腺癌。14名患者没有表达任何PG-I表位。表达至少两个PG-I表位的患者与表达单一表位或表达任何表位的患者相比，生存期较短(28比44周，P=0.0021)。MIB-1高表达患者生存期较短(25周比41周，P=0.0059)。其他参数与临床结果无关。多因素分析证实PG-I表达和MIB-1是独立的阴性预后因素。在ECM中有PG-I表达的患者比没有表达的患者预后更差。我们的结果与ECM蛋白是局部胰腺癌转移扩散的潜在屏障的假设并不相反。相反，我们强调了癌症晚期肿瘤-间质相互作用的复杂性和进一步研究的必要性。
Conflicting results have been reported on the role of extracellular matrix (ECM) proteins in pancreatic cancer. Preclinical studies suggest that the overexpression of biglycan (proteoglycan-I, PG-I), a leucine-rich protein of the ECM, may induce growth arrest of pancreatic cancer cells. The aim of this study was to assess the prognostic role of biglycan expression in pancreatic cancer. We also evaluated MIB-1 and COX-2 expressions (as potential markers of growth and aggressiveness) to better characterize the biology of the tumors. The classical pathological parameters (grading, desmoplasia, perineural, or vascular invasion) as well as molecular determinants of prognosis were examined. MIB-1 (a proliferative index associated with prognosis in most tumors), COX-2, and PG-I expressions were detected by immunohistochemistry and immunofluorescence on tissue samples from 53 patients with pancreatic cancer and reviewed by two independent pathologists. To verify PG-I expression, three rabbit sera (LF104, LF112, and LF121 from NIH, Bethesda, MA, US) were tested. Logrank test and Cox's model were applied for statistical analysis. Out of 53 patients, 40 had stage III and IV pancreatic cancer. Fourteen patients did not express any of the PG-I epitopes. The patients who expressed at least two PG-I epitopes had shorter survival compared to those with single epitope or lacking any expression (28 vs 44 weeks, P = 0.0021). The MIB-1 higher expression predicted shorter survival (25 vs 41 weeks, P = 0.0059). The other parameters were not associated with clinical outcome. Multivariate analyses confirmed PG-I expression and MIB-1 as independent negative prognostic factors. Patients who presented PG-I expression in the ECM had the worse prognosis compared to those who did not. Our results are not in contrast with the hypothesis that ECM proteins are a potential barrier to metastatic spread in localized pancreatic cancer. Rather, we underline the complexity of tumor-stroma interactions in the advanced stage of cancer and the need of further study.