9271

PIWIL1

piwi-like RNA-mediated gene silencing 1;PIWIL1;piwi-like RNA-mediated gene silencing 1

piwi homolog|piwi-like protein 1

12q24.33

protein-coding

INTRODUCTION: Combination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens. METHODS: Immunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome. RESULTS: With the tumor marker positive rate [32.0% (62/225) for SNCG; 76.9% (173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9% (252/407) for SNCG; 82.6% (336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN-), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN+). CONCLUSIONS: Multimarker phenotypes improved tumor positive rate, detecting accuracy and prognostic value. In addition, a subgroup of more aggressive tumors can be identified by evaluating Hiwi level in LN- cancer, and SNCG level in LN+ cancer.

cancer cells have countless behaviors of pluripotent embryonic stem cells and germ line cells, such as unlimited proliferation, self-renewal, and migration. expression of specific germ line and embryonic genes in tumor cells may be associated with indefinite growth and invasiveness of such cells. Developmental pluripotency factor 2 (DPPA2) and HIWI are two important developmental genes which are involved in embryonic and germ line stem cell properties. Deciphering the role of these genes seems to be necessary for understanding cancer initiation and progression. tumoral and normal tissues from 46 colorectal cancer (CRC) patients were subjected to gene expression analysis using quantitative real-time reverse transcription-polymerase chain reaction, prior to any therapeutic intervention. Overexpression of DPPA2 and HIWI was detected in 26.1 and 34.8 % of specimens, respectively. Significant correlation between DPPA2 overexpression and lymph node metastasis of the tumor cells (P=0.049) was seen in the samples with advanced stages (III/IV) of the tumor development. HIWI mRNA expression was significantly associated to the depth of tumor invasion (P=0.020) and the stage of tumorigenesis progression (P=0.030). In samples with overexpression of at least one gene, DPPA2 mRNA expression was significantly correlated to the stage of tumor (P=0.017). In the same samples, a significant correlation was observed between mRNA expression of HIWI and the stage of tumor cells (P=0.034). These results documented the important role of HIWI and DPPA2 in tumorigenesis and also in lymph node metastasis of tumor cells. Further evaluation is required to uncover the detailed role of HIWI and DPPA2 and their interactions in tumorigenesis of CRC.

BACKGROUND: PIWI protein family was found to play an important role in stem cell self-renewal. Overexpression of HIWI, the human homolog of PIWI family proteins, was found in several solid tumors, although the role of HIWI in hepatocellular carcinoma (HCC) and its prognostic value remain unclear. METHODS: HIWI expression was measured in stepwise metastatic HCC cell lines (HCCLM3, MHCC97H, MHCC97L, SMMC7721, and HepG2), the normal liver cell line (L02), and HCC tissue samples (n = 20). Proliferation and invasion were investigated in HCC cell lines undergoing HIWI target small interfering RNA transfection. Also explored was HIWI expression in HCC tissue microarrays (n = 168) for survival analysis. RESULTS: Levels of HIWI protein and mRNA were up-regulated in highly metastatic HCC cell lines (HCCLM3, MHCC97H, and MHCC97L), whereas their proliferation and invasion significantly decreased after depletion of HIWI. Intratumoral HIWI expression was higher than that of peritumoral tissue (P < .001) and positively associated with proliferating cell nuclear antigen expression (P < .001). Positive expression of intratumoral HIWI was associated with larger tumor size (P = .047) and intrahepatic metastasis (P = .027) and was an independent risk factor for overall survival (P = .007) and recurrence-free survival (P = .036), particularly in patients with low serum alpha-fetoprotein and low Edmondson-Steiner grade. CONCLUSIONS: HIWI may play a key role in HCC proliferation and metastasis and can be a potential prognostic factor for HCC after curative resection, particularly with well-differentiated HCC.