Grochola L F, Greither T, Taubert H, Möller P, Knippschild U, Udelnow A, Henne-Bruns D, Würl P
Department of General, Visceral and Transplantation Surgery, The University of Ulm, Steinhövelstrasse 9, Ulm 89075, Germany.
Br J Cancer. 2008 Oct 7;99(7):1083-8. doi: 10.1038/sj.bjc.6604653. Epub 2008 Sep 9.
Piwi proteins and their interaction with piRNAs have rapidly emerged as important contributors to gene regulation, indicating their crucial function in germline and stem cell development. However, data on the Hiwi 1 (Hiwi) gene, one of the four human Piwi homologues, are still scarce. Therefore, we investigated the Hiwi mRNA expression in microdissected PDAC tissues from patients with ductal adenocarcinoma of the pancreas (PDAC) by quantitative real-time PCR and the protein expression by immunohistochemistry. Elevated levels of Hiwi mRNA transcripts were measured in 40 out of 56 tissues and a positive immunostaining of Hiwi was detected in tumours of 21 out of 78 patients. There was no general impact of elevated Hiwi mRNA transcript levels or protein expression on survival, as tested by multivariate Cox regression and Kaplan-Meier analysis. However, men showed a significantly increased risk for tumour-related death in case of down- or upregulated expression of Hiwi mRNA (relative risk (RR)=2.78; P=0.034). In summary, we report the first analysis of Hiwi expression in PDAC and its impact on prognosis. We suggest that alterations in mRNA expression of Hiwi can increase the risk of tumour-related death in male PDAC patients.
Piwi蛋白及其与piRNA的相互作用已迅速成为基因调控的重要因素,表明它们在生殖系和干细胞发育中具有关键作用。然而,关于人类四种Piwi同源物之一的Hiwi 1(Hiwi)基因的数据仍然很少。因此,我们通过定量实时PCR研究了来自胰腺导管腺癌(PDAC)患者的显微切割PDAC组织中Hiwi mRNA的表达,并通过免疫组织化学研究了蛋白质表达。在56个组织中的40个中检测到Hiwi mRNA转录本水平升高,在78名患者中的21名患者的肿瘤中检测到Hiwi的阳性免疫染色。通过多变量Cox回归和Kaplan-Meier分析测试,Hiwi mRNA转录本水平或蛋白质表达升高对生存率没有普遍影响。然而,在Hiwi mRNA表达下调或上调的情况下,男性显示出肿瘤相关死亡风险显著增加(相对风险(RR)=2.78;P=0.034)。总之,我们报告了首次对Hiwi在PDAC中的表达及其对预后的影响进行的分析。我们认为,Hiwi mRNA表达的改变会增加男性PDAC患者肿瘤相关死亡的风险。