Microarray-based identification of CUB-domain containing protein 1 as a potential prognostic marker in conventional renal cell carcinoma.

PURPOSE: Renal cell carcinoma (RCC) is characterized by a variable and unpredictable clinical course. Thus, accurate prediction of the prognosis is important in clinical settings. We conducted microarray-based study to identify a novel prognostic marker in conventional RCC. PATIENTS AND METHODS: The present study included the patients surgically treated at Kyoto University Hospital. Gene expression profiling of 39 samples was carried out to select candidate prognostic markers. Quantitative real-time PCR of 65 samples confirmed the microarray experiment results. Finally, we evaluated the significance of potential markers at their protein expression level by immunohistochemically analyzing 230 conventional RCC patients. RESULTS: Using expression profiling analysis, we identified 14 candidate genes whose expression levels predicted unfavorable disease-specific survival. Next, we examined the expression levels of nine candidate genes by quantitative real-time PCR and selected CUB-domain containing protein 1 (CDCP1) for further immunohistochemical analysis. Positive staining for CDCP1 inversely correlated with disease-specific and recurrence-free survivals. In multivariate analysis including clinical/pathological factors, CDCP1 staining was a significant predictor of disease-specific and recurrence-free survivals. CONCLUSIONS: We identified CDCP1 as a potential prognostic marker for conventional RCC. Further studies might be required to confirm the prognostic value of CDCP1 and to understand its function in RCC progression.

Glucocorticoid-induced granzyme A expression can be used as a marker of glucocorticoid sensitivity for acute lymphoblastic leukemia therapy.

The ability of glucocorticoids (GC) to efficiently kill lymphoid cells has led to their inclusion in essentially all chemotherapy procedures used to treat acute lymphoblastic leukemia (ALL). GC sensitivity is an important prognostic factor in ALL treatment, and it is used to classify patients into risk groups. Clinical assessment for GC sensitivity is very time-consuming, however. We have recently found that granzyme A (GZMA) mediates GC-induced apoptosis in ALL-derived cell line 697. In this study we examined the correlation between GC sensitivity and GC-induced GZMA expression by using seven established cell lines derived from ALL patients. The apoptosis assay showed four cell lines were GC-sensitive and three were GC-resistant. GC treatment markedly enhanced GZMA expression in GC-sensitive cell lines only, and not in GC-resistant cell lines. GC-induced GZMA expression also correlated well with the amount of GC-induced apoptosis. GC-induced GZMA expression could thus be a useful early biomarker for "personalized" ALL therapy.

An ultrasensitive new DNA microarray chip provides gene expression profiles for preoperative esophageal cancer biopsies without RNA amplification.

OBJECTIVES: Gene expression profiling using pretreatment biopsies has been limited due to their small sample sizes. This study evaluated the usefulness of an ultrasensitive new DNA microarray chip, which has a unique array structure, for the clinical diagnosis of esophageal cancer using preoperative biopsies. METHODS: Paired cancer and normal esophageal epithelial tissues from 56 patients who underwent esophagectomy and from 48 patients who underwent preoperative endoscopy were studied. Among 2 feature gene sets selected by a reference DNA chip discriminating malignant status of samples, 20 feature genes were selected for the development of the new DNA chip. The new DNA chip was hybridized with 0.1 mug of total RNA per slide without RNA amplification. RESULTS: Twenty feature genes, including RRM-2 and XRCC-3, for the new DNA chip could discriminate cancer from noncancer at a 95.2% rate of accuracy in 42 biopsies (sensitivity 95.7%, specificity 94.7%). A receiver operating characteristic (ROC) curve analysis showed that the area under ROC curve for the prediction was 0.966. CONCLUSIONS: The gene expression profiles from the preoperative biopsies could diagnose esophageal cancer accurately, using the ultrasensitive DNA chip without RNA amplification. This new DNA chip technology might contribute further to the development of customized therapeutic strategies for various cancer patients.

In vitro growth suppression of human glioma cells by a 16-mer oligopeptide: a potential new treatment modality for malignant glioma.

Fibroblast growth factor-2 (FGF-2) is involved as an autocrine growth factor in the autonomous proliferation of glioma cells. To develop a new strategy for treating patients with glioma, we studied the effect on human glioma cells of a 16-mer oligopeptide with conformational similarity to the putative receptor-binding domain of FGF-2. A synthesized oligonucleotide was assessed its receptor-binding activity by BIAcore instrument. Its biological effect on glioma cell lines was examined in vitro by MTT assay. The peptide suppressed the in vitro growth of human glioma cells U87MG, T98G and U251MG cells, but not of A431 cells whose growth is not dependent on FGF-2. Apoptotic bodies were noted after 24-h incubation in the presence of the peptide; Ac-YVAD-CHO, a caspase-3 inhibitor, suppressed apoptosis. Furthermore, we examined the modulation of the cytotoxic effect of anticancer drugs by the oligopeptide. The addition of this oligopeptide to the chemotherapeutic agents CDDP, ACNU and VP16 had additive effects in vitro. These results suggest that the pathway of the FGF-2 autocrine loop through the FGF receptor plays an important role in the proliferation of glioma cells. New drugs targeting this loop may be highly effective in treating FGF-2-dependent tumors. Our results suggest that its addition to the therapeutic arsenal may lead to improved treatment regimens for patients with FGF-2-dependent tumors.