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足细胞毒素是胰腺导管腺癌预后不良的标志物。

Podocalyxin Is a Marker of Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

作者信息

Saukkonen Kapo, Hagström Jaana, Mustonen Harri, Juuti Anne, Nordling Stig, Fermér Christian, Nilsson Olle, Seppänen Hanna, Haglund Caj

机构信息

Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland; Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland.

Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, FIN-00014 University of Helsinki, Helsinki, Finland; Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, FIN-00014 University of Helsinki, Helsinki, Finland.

出版信息

PLoS One. 2015 Jun 8;10(6):e0129012. doi: 10.1371/journal.pone.0129012. eCollection 2015.

Abstract

AIM OF THE STUDY

Podocalyxin-like 1 is a transmembrane glyco-protein whose overexpression associates in many cancers with poor prognosis and unfavorable clinicopathological characteristics. Until now, its prognostic value has never been studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate podocalyxin expression in PDAC by a novel monoclonal antibody and a commercially available polyclonal antibody.

PATIENTS AND MATERIALS

With tissue microarrays and immuno-histochemistry, podocalyxin expression evaluation involved 168 PDAC patients. The associations of the podocalyxin tumor expression with clinicopathological variables were explored by Fisher's exact test and the linear-by-linear test. Survival analyses were by Kaplan-Meier analysis and the Cox proportional hazard model.

RESULTS

The polyclonal antibody revealed membranous podocalyxin expression in 73 (44.0%) specimens and the monoclonal antibody was highly expressed in 36 (21.8%) cases. Membranous expression by the polyclonal antibody was associated with T classification (p=0.045) and perineural invasion (p=0.005), and high expression by the mono-clonal antibody with poor differentiation (p=0.033). High podocalyxin expression associated significantly with higher risk of death from PDAC by both the polyclonal antibody (hazard ratio (HR) = 1.62; 95% confidence interval (CI) 1.12-2.33; p=0.01) and the monoclonal antibody (HR = 2.10, 95% CI 1.38-3.20; p<0.001). The results remained significant in multivariate analysis, adjusted for age, gender, stage, lymph node ratio (≥/< 20%), and perivascular invasion (respectively as HR = 2.03; 95% CI 1.32-3.13, p=0.001; and as HR = 2.36; 95% CI 1.47-3.80, p<0.001).

CONCLUSION

We found podocalyxin to be an independent factor for poor prognosis in PDAC. To our knowledge, this is the first such report of its prognostic value.

摘要

研究目的

足突细胞粘附分子样1是一种跨膜糖蛋白,其过表达在许多癌症中与预后不良及不利的临床病理特征相关。迄今为止,其在胰腺导管腺癌(PDAC)中的预后价值尚未得到研究。本研究的目的是通过一种新型单克隆抗体和一种市售多克隆抗体来研究足突细胞粘附分子在PDAC中的表达情况。

患者和材料

利用组织微阵列和免疫组织化学,对168例PDAC患者进行了足突细胞粘附分子表达评估。通过Fisher精确检验和线性-线性检验探讨足突细胞粘附分子肿瘤表达与临床病理变量之间的关联。生存分析采用Kaplan-Meier分析和Cox比例风险模型。

结果

多克隆抗体显示73例(44.0%)标本中有膜性足突细胞粘附分子表达,单克隆抗体在36例(21.8%)病例中高表达。多克隆抗体的膜性表达与T分期(p=0.045)和神经周围浸润(p=0.005)相关,单克隆抗体的高表达与低分化(p=0.033)相关。多克隆抗体(风险比(HR)=1.62;95%置信区间(CI)1.12-2.33;p=0.01)和单克隆抗体(HR=2.10,95%CI 1.38-3.20;p<0.001)的高足突细胞粘附分子表达均与PDAC死亡风险显著相关。在对年龄、性别、分期、淋巴结比例(≥/<20%)和血管周围浸润进行校正的多变量分析中,结果仍然显著(分别为HR=2.03;95%CI 1.32-3.13,p=0.001;以及HR=2.36;95%CI 1.47-3.80,p<0.001)。

结论

我们发现足突细胞粘附分子是PDAC预后不良的一个独立因素。据我们所知,这是关于其预后价值的首次此类报告。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ded/4459962/17eccf2feed4/pone.0129012.g001.jpg

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