YRNA expression predicts survival in bladder cancer patients.

BACKGROUND: Non-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed. RESULTS: All YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients' overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma. CONCLUSIONS: The expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.

Genome-wide expression profiling reveals new insights into pathogenesis and progression of testicular germ cell tumors.

Testicular germ cell tumors (GCT) are the most frequent malignancy in young adults and arise from intratubular germ cell neoplasia undetermined (IGCNU, also referred to as carcinoma in situ, CIS). To determine the transcriptional programs involved in the transition from normal germ cells to GCT, and to further elucidate genetic differences between seminomas and non-seminomatous GCT the global expression profile of 12 neoplastic and 3 normal testicular tissues were investigated by whole genome cDNA microarrays. Transcriptional differences between seminomas and embryonal carcinomas were determined and gene signatures characterizing histological subtypes of GCT were identified. The most significant difference between seminomas and embryonal carcinomas was the expression of spermatogenesis-associated genes (PRAME, MAGEA4, SPAG1, HPX) in seminomas and regulatory genes DNMT3B and SOX2 as well as small molecular weight keratins KRT8, KRT18 in embryonal carcinomas. The expression of several selected genes (CK18, MAGE-A4, SOX2, DNMT3B, CD30, KIT) was studied by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR) in a large collective of GCT. In summary, our data identified tumor type-specific gene signatures of GCT and provided new insights into genetic pathways driving the transition to seminomas and embryonal carcinomas from their respective precursor lesions.

Gene expression profiling identifies new biological markers of neoplastic germ cells.

BACKGROUND: There is only limited knowledge about gene expression in human testicular germ cell tumors of adolescents and adults (TGCTs), and, in particular in its preinvasive stage intratubular germ cell neoplasia unclassified (IGCNU). MATERIALS AND METHODS: Global gene expression was studied in 10 invasive human testicular germ cell tumors (TGCTs), 7 intratubular germ cell neoplasia unclassified (IGCNU) and 3 normal testes. The pattern of expression of several genes was studied by immunohistochemistry on tissue microarrays containing 126 TGCTs, IGCNU, normal testes and in 5 fetal testes. RESULTS: RAS-related genes (KRAS2, RALA, RAB39B) and various core markers of embryonic stem cells were overexpressed in IGCNU compared to normal testes. CD9, PODXL and centromere-specific histone-H3-like protein CENPA were specifically identified in IGCNU, seminomas, embryonal carcinomas and in fetal gonocytes. Embryonic stem cell regulator SOX2 and downstream targets of the Nodal pathway were up-regulated in embryonal carcinoma only but not in IGCNU/seminoma. Preliminary data revealed that the expression profile of IGCNU is dependent on the histology of the adjacent invasive tumor. CONCLUSION: Our study determined the genes involved in early pathogenetic events of neoplastic germ cell formation, provided new insights into genetic pathways driving the transition of embryonal carcinoma and seminoma from IGCNU and identified new biomarkers of neoplastic germ cells such as CD9, CENPA and PODXL.