据近期网络版《国际癌症杂志》上的一篇文章报告，一类小分子RNA可区分胰腺癌组织和正常或良性胰腺组织，也许将为胰腺癌的诊断和治疗提供新的线索。
在美国，胰腺癌导致的死亡人数在所有癌症中高居第四位。预计今年将会有33700美国人罹患胰腺癌，并且另外将有32300人死于该病。胰腺癌死亡率极高，新发病例数几乎等于死亡人数，这主要是因其难以早期诊断，而且治疗方法有限。
来自俄亥俄州立大学综合性肿瘤中心的癌症研究人员，检测比较了人类胰腺癌组织与周围的正常组织和对照组织中小分子RNA（miRNA）表达水平，发现在肿瘤组织中大约有100种不同的miRNA通常表达水平非常高，而它们在正常胰腺组织中的水平并不高。该结果提示miRNA作为一种标志或表达模式，将为研究胰腺癌的发生提供新的线索。它们可能会导致新的分子技术出现，使医生们能够更好的诊断和治疗胰腺癌。
俄亥俄州立大学综合性肿瘤中心研究员、药学系副教授ThomasD.Schmittgen与俄克拉荷马州大学医学中心外科主任RussellPostier，及其同事们合作完成了此项研究。他们检测比较了225种miRNA在患者胰腺肿瘤组织和邻近正常组织、正常胰腺组织样本以及9个胰腺癌细胞系中的表达水平。由于该方法是基于一种叫做实时PCR表达谱的技术，其敏感性高且只需要极少量的组织。
结果显示，很多miRNA在胰腺癌中的水平与同一患者良性组织或者正常胰腺组织中水平大不相同。大部分miRNA在胰腺癌中处于相当高的水平，这提示开发可以抑制它们的药物将可能为胰腺癌提供新的治疗方法。这也意味着基于miRNA表达水平的检查可能有助于胰腺癌的诊断。
International Journal of Cancer，Volume 120, Issue 9 , Pages 1842 - 1846
Published Online: 31 Jan 2007
HPV16-E6 mRNA is superior to cytokeratin 19 mRNA as a molecular marker for the detection of disseminated tumour cells in sentinel lymph nodes of patients with cervical cancer by quantitative reverse-transcription PCR
Norman Häfner 1, Mieczyslaw Gajda 2, Christopher Altgassen 1 3, Hermann Hertel 1 4, Christiane Greinke 1, Peter Hillemanns 4, Achim Schneider 5, Matthias Dürst 1 *
1Frauenklinik der Friedrich-Schiller-Universität Jena, Jena, Germany
2Institut für Pathologie, Klinikum der Friedrich-Schiller-Universität Jena, Jena, Germany
3Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
4Frauenklinik der Medizinischen Hochschule Hannover, Hannover, Germany
5Frauenklinik mit Hochschulambulanz der Charité, Campus Benjamin Franklin und Campus Mitte, Berlin, Germany
email: Matthias Dürst (matthias.duerst@med.uni-jena.de)
*Correspondence to Matthias Dürst, Frauenklink der FSU Jena, Bachstrasse 18, 07743 Jena, Germany
Fax: +49-3641-934272.
Keywords
cervical cancer ?disseminated tumour cells ?molecular markers ?HPV16-E16 ?cytokeratin 19 ?quantitative RT-PCR
Abstract
About 10-15% of patients with cervical cancer suffer from recurrence despite histologically negative lymph nodes (pN0). Occult micrometastases or small tumour cell clusters may contribute to disease outcome. The aim of this study was to compare at the RNA level 2 known tumour-associated genes, HPV16-E6 and cytokeratin 19 (CK19), as molecular markers for the detection of disseminated tumour cells. Real-time reverse transcription PCR technology was used to quantify gene expression in histologically positive and negative sentinel lymph nodes (SLN) from 70 patients with cervical cancer. Lymph nodes from noncancer patients were used as controls. Calculated copy numbers were normalised to the geometric average of the most stable housekeeping genes. We observed a good correlation (R = 0.915) between the expression of both markers in SLN with histologically confirmed metastases. However, marker gene expression differed considerably in histologically negative nodes: CK19 transcripts were detected in 90 of 112 SLN (80.4%), whereas only 38 nodes (33.9%) were positive for HPV16 E6 mRNA. In particular, 62 of 74 SLN, which were negative by histology, and HPV16 E6 mRNA expressed CK19 mRNA. Moreover, 8 of 10 lymph nodes from noncancer patients expressed CK19 mRNA. Systematic errors due to RNA degradation or incomplete cDNA could be ruled out. It is concluded that HPV16 E6 mRNA is more specific and more sensitive for the detection of tumour cells in SLN than CK19 mRNA. The specificity of CK19 is limited because of low level expression in uninvolved pelvic lymph nodes. © 2007 Wiley-Liss, Inc.
Received: 9 October 2006; Accepted: 6 November 2006
