Expression of PRUNE2 mRNA and its positive correlation with non-coding RNA PCA3 in leiomyosarcoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Our previous study shows that PURNE2 mRNA plays an important role in the differential diagnosis of leiomyosarcoma and gastrointestinal stromal tumor (GIST). Non-coding RNA PCA3 locates in the intron of PRUNE2 and may play a role in PRUNE2 expression. The aim of this study was to explore the expression of PCA3 mRNA and PRUNE2 in leiomyosarcoma and their correlation.</p><p><b>METHODS</b>The expression of PRUNE2 mRNA was analyzed by agilent gene expression microarray CHIP in 31 leiomyosarcomas and 37 GISTs, and the correlation of the PRUNE2 expression and prognosis of leiomyosarcoma was predicted. Real-Time PCR assay was used to detect the mRNA levels of PCA3 and PRUNE2 in 13 leiomyosarcomas and to investigate their correlation. Seven prostate cancer tissues were used as control of PCA3.</p><p><b>RESULTS</b>The level of PRUNE2 mRNA expression was significantly higher in the 31 leiomyosarcomas than that in the 37 GISTs, and the level of PRUNE2 mRNA expression was correlated with survival of the leiomyosarcoma patients. Compared with prostate cancer, the non-coding RNA PCA3 expression level was significantly lower in leiomyosarcoma, and it had no correlation with the prognosis of leiomyosarcoma. Most importantly, the PRUNE2 and PCA3 mRNA expressions were both upregulated in leiomyosarcoma and showed a significant positive correlation.</p><p><b>CONCLUSIONS</b>Our findings demonstrate for the first time that PRUNE2 expression is correlated with the survival of leiomyosarcoma patients. Furthermore, non-coding RNA PCA3, which locates in the intron of PRUNE2, has a significant positive correlation with PRUNE2 and may play an important role in the pathogenesis of leiomyosarcoma.</p>

Tumor-associated methylation of the putative tumor suppressor AJAP1 gene and association between decreased AJAP1 expression and shorter survival in patients with glioma / 癌症

Allelic loss of the short arm of chromosome 1 has been observed frequently in a wide spectrum of cancers, most frequently in oligodendroglioma. In our previous studies, we evaluated 177 oligodendroglial tumor samples and identified the AJAP1 gene (formerly Shrew1) in the consensus region of deletion. AJAP1 is a transmembrane protein found in adheren junctions and functions to inhibit glioma cell adhesion and migration. Whereas a putative tumor suppressor gene, we did not detect AJAP1 gene mutations. In subsequent studies, we found that AJAP1 was underexpressed in oligodendrogliomas relative to normal brain tissues. Bioinformatic analysis revealed the presence of CpG islands in the promoter of AJAP1. Methylation analysis of the AJAP1 promoter identified hypermethylation in 21% of oligodendrogliomas (n =27), and the degree of methylation correlated with low levels of AJAP1 expression (P = 0.045). The AJAP1 promoter was also highly methylated in a wide spectrum of cell lines (n = 22), including cell lines of glioblastoma. Analysis of the National Cancer Institute's REMBRANDT dataset, which contains 343 glioma samples, indicated that low AJAP1 gene expression was associated with decreased survival. Thus, both genetic (gene deletion) and epigenetic alterations (promoter methylation) are likely mechanisms that inactivate the putative tumor suppressor AJAP1 in gliomas, which contributes to poor prognosis.