High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer
TRANSLATIONAL ONCOLOGY
Authors: Sikic, Danijel; Breyer, Johannes; Hartmann, Arndt; Burger, Maximilian; Erben, Philipp; Denzinger, Stefan; Eckstein, Markus; Stohr, Robert; Wach, Sven; Wullich, Bernd; Keck, Bastian; Wirtz, Ralph M.; Otto, Wolfgang
Abstract
INTRODUCTION: High-risk non-muscle-invasive bladder cancer (NMIBC) remains challenging given the high probability of progression. Given that the androgen receptor (AR) has been discussed as a possible factor in the development and progression of bladder cancer, we investigated the predictive value of AR in stage pT1 NMIBC. MATERIALS AND METHODS: We retrospectively analyzed the clinical data and AR mRNA expression in 296 patients with stage pT1 NMIBC who underwent a transurethral resection of the bladder. The mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured by reverse transcription quantitative real-time polymerase chain reaction. AR expression was also correlated to KRT5 and KRT20 mRNA expression. RESULTS: Kaplan-Meier analysis indicated that high AR1 mRNA expression >= 35.47 is associated with statistically significant better recurrence-free survival (RFS) (P = .0007), progression-free survival (PFS) (P = .0420), and cancer-specific survival (CSS) (P = .0050). Multivariate Cox regression analysis revealed that high AR1 mRNA expression is an independent prognostic marker for RFS (P = .0029) and CSS (P = .0119). Spearman rank correlation revealed a significant positive association between mRNA expression of AR1 and KRT5 (r(s): 0.3171, P < .0001) as well as a negative association with multifocal tumors (r(s): 0.1478, P < .0109). No association was noted between AR1 expression and tumor grade, concomitant CIS, gender, tumor size, and KRT20 in patients with stage T1 NMIBC. CONCLUSIONS: AR mRNA expression can predict RFS and CSS in patients with stage T1 NMIBC. Further studies are necessary to refine the relevance of AR mRNA expression compared with immunohistochemically detectable AR expression.
Red-emitting FIT-PNAs: "On site" detection of RNA biomarkers in fresh human cancer tissues
BIOSENSORS & BIOELECTRONICS
Authors: Hashoul, Dina; Shapira, Rachel; Falchenko, Maria; Tepper, Odelia; Paviov, Vera; Nissan, Aviram; Yavin, Eylon
Abstract
To date, there are limited approaches for the direct and rapid visualization (on site) of tumor tissues for pathological assessment and for aiding cytoreductive surgery. Herein, we have designed FIT-PNAs (forced-intercalation-peptide nucleic acids) to detect two RNA cancer biomarkers. Firstly, a lncRNA (long noncoding RNA) termed CCAT1, has been shown as an oncogenic lncRNA over-expressed in a variety of cancers. The latter, an mRNA termed KRT20, has been shown to be over-expressed in metastases originating from colorectal cancer (CRC). To these FIT-PNAs, we have introduced the bis-quinoline (BisQ) cyanine dye that emits light in the red region (605-610 nm) of the visible spectrum. Most strikingly, spraying fresh human tissue taken from patients during cytoreductive surgery for peritoneal metastasis of colon cancer with an aqueous solution of CCAT1 FIT-PNA results in bright fluorescence in a matter of minutes. In fresh healthy tissue (from bariatric surgeries), no appreciable fluorescence is detected. In addition, a non-targeted FIT-PNA shows no fluorescent signal after spraying this FIT-PNA on fresh tumor tissue emphasizing the specificity of these molecular sensors. This study is the first to show on-site direct and immediate visualization of an RNA cancer biomarker on fresh human cancer tissues by topical application (spraying) of a molecular sensor.