Piwi proteins and their interaction with piRNAs have rapidly emerged as

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. the risk of tumour-related death in male PDAC patients. Keywords: Hiwi, prognosis, pancreatic carcinoma, tissue microdissection Current stem cell genetic research provides only scarce data on Hiwi 1 (Hiwi) C one of four human homologues of the Piwi gene family C despite growing focus of studies around the 360A supplier latter and its interacting RNAs (piRNAs), for which a key function in transcriptional gene silencing and germline/stem cell development in flies and mammals has been exhibited (Aravin et al, 2007; Seto et al, 2007; Farazi et al, 2008). Data on Piwi proteins, a subfamily of Argonaute proteins, highlight their impressive biological capacities, such as biogenesis/regulation of small RNAs, control of protein synthesis and mRNA stability, showing conserved functions in maintenance and self-renewal of stem cells (Seto et al, 2007; Hutvagner et al, 2008). It has been suggested that deregulation of stem cell self-renewal may cause the development of malignancies because normal stem cells share several similarities with so-called tumour stem cells, for example, the ability to self-renew and a relative resistance to drugs (Soltysova et al, 2005; Chen et al, 2007; Taubert et al, 2007a). Besides being expressed abundantly in germline cells of human testes, Hiwi’s 360A supplier enhanced expression was detected in Rabbit polyclonal to AIPL1 testicular seminomas, which 360A supplier originate from embryonic germ cells with retention of a germ cell phenotype (Qiao et al, 2002). This has given rise to the assumption that Hiwi overexpression may be involved in the development of germ cell malignancy, prompting further investigation on other human malignancies. Consequently, it has been shown that expression of the Hiwi gene in human gastric cancer was associated with the proliferation of cancer cells (Liu et al, 2006). Moreover, in patients with soft-tissue sarcoma, elevated Hiwi mRNA transcript levels were associated with a significantly increased risk of tumour-related death (Taubert et al, 2007a, 2007b). However, Hiwi was not detectable in leukaemia cell lines (Sharma et al, 2001). Ductal adenocarcinoma of the pancreas (PDAC), a dismal disease with a late clinical presentation and a very poor overall prognosis (Yeo et al, 2002), seems to be an interesting subject to investigate with regards to the involvement of stem cell-associated genes and Hiwi in particular. The main features of PDACCaggressive biological phenotype, early local invasion with high metastatic potential and a high resistance to radiation and chemotherapy (Yeo et al, 2002)Csuggest the involvement of cells with stem cell characteristics in PDAC. Analysis of the stem cell-associated gene Hiwi in this malignancy might provide important clues to the understanding of this disease. Besides the above listed tumour entities, no studies on other malignancies, particularly on PDAC, around the involvement of Hiwi expression in tumour development have been reported, and the impact of Hiwi expression on patients’ prognosis has only been studied in soft-tissue sarcomas yet (Taubert et al, 2007a, 2007b). Therefore, the aim of our study was to investigate the expression profile of Hiwi and its impact on prognosis in PDAC patients. Materials and methods Patients We analysed a cohort of patients who underwent 360A supplier primary medical procedures for PDAC in the years 2001C2005 in our clinic (Department of Surgery 1, University of Ulm, Germany). Paraffin-embedded tissue of 78 patients (31 females and 47 males, age range 34C80 years; mean age 61.1 years) was obtained. Furthermore, fresh-frozen tissue of 56 patients (22 females and 34 males, age range 34C80 years; mean age 61.7 years) was conserved. All patients from whom fresh-frozen tissue suitable for microdissection (sufficient amount of neoplastic cells per sample (total of >4000 cells per patient) and intact RNA (as tested with Agilent Bioanalyzer, 360A supplier see below) was obtained were included in the study. The mean observation time was 15.99 (range 1C61) months and the median survival rate was 15.26 (range 1C52) months. Four patients died from non-tumour-related causes. None of the patients has received neoadjuvant chemo- or radiotherapeutic treatment. All patients included in the study gave written informed consent. The approval of the local ethics committee was obtained. Microdissection and QRTCPCR analysis Fresh-frozen tissue samples from 56 PDAC patients were microdissected to exclude stromal tissue and highly enrich neoplastic cells.

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