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胰腺癌的分子标志物:发展与临床相关性

Molecular markers of pancreatic cancer: development and clinical relevance.

作者信息

Fry Lucia C, Mönkemüller Klaus, Malfertheiner Peter

机构信息

Division of Gastroenterology, Otto-von-Guericke University, Magdeburg, Germany.

出版信息

Langenbecks Arch Surg. 2008 Nov;393(6):883-90. doi: 10.1007/s00423-007-0276-0. Epub 2008 Feb 12.

Abstract

BACKGROUND

The prognosis of pancreatic cancer remains poor, mainly because of its aggressive biological behaviour and late clinical diagnosis, which precludes the application of appropriate curative therapies. Therefore, one of the major goals in clinical pancreatology is to find molecular markers, specific and sensitive enough to make an early and correct diagnosis of pancreatic cancer, before it has disseminated and become untreatable.

OBJECTIVE

This overview article explores the potential utility of current molecular markers for the diagnosis of pancreatic cancer.

RESULTS

There is a wide array of serum-based and tissue-based markers for pancreatic cancer. Serum-based molecular markers include CA 19-9, CA 125, M2-PK and secreted proteins. A tissue can be used to test genetic mutations such as K-ras, inactivation of tumour suppressor genes (e.g. p16, p53), mucins, telomerase activity, growth factors, DNA methylation, and global gene expression of cDNA microarrays, mitochondrial mutations and proteomics. None of these markers is currently useful for the detection of early pancreatic cancer. In clinical practice, the most commonly accepted use of CA 19-9 is to assess the prognosis and monitor the response to therapy.

CONCLUSIONS

Many molecular markers have been proposed for the early diagnosis of PC, but most are not ready to be included as part of the routine diagnostic algorithm because they still lack sensitivity, specificity or reproducibility. CA 19-9 remains the most useful molecular marker for the diagnosis and follow-up of clinically and radiological evident pancreatic cancer.

摘要

背景

胰腺癌的预后仍然很差,主要是因为其侵袭性的生物学行为和临床诊断较晚,这使得无法应用适当的根治性治疗方法。因此,临床胰腺病学的主要目标之一是找到足够特异和敏感的分子标志物,以便在胰腺癌扩散并变得无法治疗之前进行早期和正确的诊断。

目的

这篇综述文章探讨了当前分子标志物在胰腺癌诊断中的潜在用途。

结果

有大量基于血清和基于组织的胰腺癌标志物。基于血清的分子标志物包括CA 19-9、CA 125、M2-PK和分泌蛋白。组织可用于检测基因突变,如K-ras、肿瘤抑制基因失活(如p16、p53)、粘蛋白、端粒酶活性、生长因子、DNA甲基化以及cDNA微阵列的整体基因表达、线粒体突变和蛋白质组学。目前这些标志物均无助于早期胰腺癌的检测。在临床实践中,CA 19-9最常用的用途是评估预后和监测治疗反应。

结论

已提出许多分子标志物用于胰腺癌的早期诊断,但大多数尚未准备好纳入常规诊断算法,因为它们仍缺乏敏感性、特异性或可重复性。CA 19-9仍然是临床和影像学确诊的胰腺癌诊断及随访中最有用的分子标志物。

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