據(jù)近期網(wǎng)絡(luò)版《國際癌癥雜志》上的一篇文章報(bào)告,，一類小分子RNA可區(qū)分胰腺癌組織和正?；蛄夹砸认俳M織,，也許將為胰腺癌的診斷和治療提供新的線索,。
在美國,，胰腺癌導(dǎo)致的死亡人數(shù)在所有癌癥中高居第四位,。預(yù)計(jì)今年將會(huì)有33700美國人罹患胰腺癌,，并且另外將有32300人死于該病。胰腺癌死亡率極高,，新發(fā)病例數(shù)幾乎等于死亡人數(shù),，這主要是因其難以早期診斷，而且治療方法有限,。
來自俄亥俄州立大學(xué)綜合性腫瘤中心的癌癥研究人員,，檢測(cè)比較了人類胰腺癌組織與周圍的正常組織和對(duì)照組織中小分子RNA（miRNA）表達(dá)水平，發(fā)現(xiàn)在腫瘤組織中大約有100種不同的miRNA通常表達(dá)水平非常高,，而它們?cè)谡Ｒ认俳M織中的水平并不高,。該結(jié)果提示miRNA作為一種標(biāo)志或表達(dá)模式，將為研究胰腺癌的發(fā)生提供新的線索,。它們可能會(huì)導(dǎo)致新的分子技術(shù)出現(xiàn),，使醫(yī)生們能夠更好的診斷和治療胰腺癌。
俄亥俄州立大學(xué)綜合性腫瘤中心研究員,、藥學(xué)系副教授ThomasD.Schmittgen與俄克拉荷馬州大學(xué)醫(yī)學(xué)中心外科主任RussellPostier,，及其同事們合作完成了此項(xiàng)研究,。他們檢測(cè)比較了225種miRNA在患者胰腺腫瘤組織和鄰近正常組織、正常胰腺組織樣本以及9個(gè)胰腺癌細(xì)胞系中的表達(dá)水平,。由于該方法是基于一種叫做實(shí)時(shí)PCR表達(dá)譜的技術(shù),，其敏感性高且只需要極少量的組織。
結(jié)果顯示,，很多miRNA在胰腺癌中的水平與同一患者良性組織或者正常胰腺組織中水平大不相同,。大部分miRNA在胰腺癌中處于相當(dāng)高的水平，這提示開發(fā)可以抑制它們的藥物將可能為胰腺癌提供新的治療方法,。這也意味著基于miRNA表達(dá)水平的檢查可能有助于胰腺癌的診斷,。
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 ([email protected])
*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
