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神经生长因子受体的表达与人类胰腺癌的进展和预后相关。

Expression of nerve growth factor receptors is correlated with progression and prognosis of human pancreatic cancer.

作者信息

Dang Chengxue, Zhang Yong, Ma Qingyong, Shimahara Yasuyuki

机构信息

Department of Surgical Oncology, First Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

J Gastroenterol Hepatol. 2006 May;21(5):850-8. doi: 10.1111/j.1440-1746.2006.04074.x.

DOI:10.1111/j.1440-1746.2006.04074.x
PMID:16704535
Abstract

BACKGROUND AND AIM

The aim of the present study was to investigate the prognostic value of the two types of nerve growth factor receptors (NGFR), namely high-affinity receptor TrkA and low-affinity receptor p75NGFR, in pancreatic cancer.

METHODS

The mRNA expression of NGFR for TrkA and p75NGFR was examined in 56 human primary pancreatic cancers using real-time quantitative reverse transcription-polymerase chain reaction.

RESULTS

Nerve growth factor (NGF) receptors were found in all tumor specimens. It appears that the growth of pancreatic cancer cells stimulated by NGF depended on the expression levels and the ratio of TrkA to p75NGFR. TrkA and p75NGFR were negatively correlated and both were associated with abdominal or back pain and perineural invasion. Regarding this, patients with high TrkA expression levels exhibited more frequent perineural invasion and a higher degree of pain, whereas the results of p75NGFR were opposite. For Cox univariate analyses in the overall survival study, high expression of p75NGFR was associated with longer overall survival, but TrkA exhibited opposite effects and included an effect on perineural invasion and pain. Histoprognostic grading, tumor size and node involvement were not prognostic factors. In Cox multivariate analyses, TrkA and p75NGFR were both prognostic parameters.

CONCLUSIONS

The present study found that the expression of TrkA in pancreatic cancer is a marker of tumor aggressiveness. Conversely, we also found that elevated p75NGFR expression is associated with a favorable prognosis. We demonstrated that NGF exerts both stimulatory and inhibitory effects on pancreatic cancers, with the overall effect determined by the expression levels and the ratio of TrkA to p75NGFR.

摘要

背景与目的

本研究旨在探讨两种神经生长因子受体(NGFR),即高亲和力受体TrkA和低亲和力受体p75NGFR在胰腺癌中的预后价值。

方法

采用实时定量逆转录-聚合酶链反应检测56例人原发性胰腺癌中TrkA和p75NGFR的NGFR mRNA表达。

结果

在所有肿瘤标本中均发现神经生长因子(NGF)受体。似乎NGF刺激的胰腺癌细胞生长取决于TrkA的表达水平以及TrkA与p75NGFR的比例。TrkA和p75NGFR呈负相关,且均与腹痛或背痛及神经周围侵犯有关。就此而言,TrkA表达水平高的患者神经周围侵犯更频繁且疼痛程度更高,而p75NGFR的结果则相反。在总生存研究的Cox单因素分析中,p75NGFR高表达与更长的总生存相关,但TrkA表现出相反的作用,且对神经周围侵犯和疼痛有影响。组织预后分级、肿瘤大小和淋巴结受累不是预后因素。在Cox多因素分析中,TrkA和p75NGFR均为预后参数。

结论

本研究发现胰腺癌中TrkA的表达是肿瘤侵袭性的标志物。相反,我们还发现p75NGFR表达升高与良好预后相关。我们证明NGF对胰腺癌既有刺激作用又有抑制作用,总体作用由TrkA的表达水平以及TrkA与p75NGFR的比例决定。

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