Family with sequence similarity 13C (FAM13C) overexpression is an independent prognostic marker in prostate cancer

Christoph Burdelski,Alexander Haese,Nathaniel Melling,Guido Sauter,Martina Kluth,Till Krech,Waldemar Wilczak,Frank Jacobsen,Stefan Steurer,Andrea Hinsch,Corinna Wittmer,Thorsten Schlomm,Hans Uwe Michl,Jakob R Izbicki,Ronald Simon,Sarah Minner,Maria Christina Tsourlakis,Laura Borcherding,Patrick Lebok,Philipp Weigand,Franziska Büscheck,Christina Möller‐Koop ,Till S Clauditz ,Claudia Hube‐Magg

doi:10.18632/oncotarget.16357

Abstract

FAM13C, a gene with unknown function is included in several mRNA signatures for prostate cancer aggressiveness. To understand the impact of FAM13C on prognosis and its relationship to molecularly defined subsets, we analyzed FAM13C expression by immunohistochemistry on a tissue microarray containing 12,400 prostate cancer specimens. Results were compared to phenotype, ERG status, genomic deletions of 3p, 5q, 6q and PTEN, and biochemical recurrence. FAM13C was detectable in cell nuclei of cancerous and non-neoplastic prostate cells. 67.5% of 9,633 interpretable cancers showed FAM13C expression: strong in 28.3%, moderate in 24.6% and weak in 14.6%. Strong FAM13C expression was linked to advanced pT stage, high Gleason grade, positive lymph node status, and early biochemical recurrence (p < 0.0001 each). FAM13C expression was associated with TMPRSS2:ERG fusions. It was present in 85% of ERG positive but in only 54% of ERG negative cancers (p < 0.0001), and in 91.1% of PTEN deleted but in only 69.2% of PTEN non-deleted cancers (p < 0.0001). The prognostic role of FAM13C expression was independent of classical and quantitative Gleason grade, pT stage, pN stage, surgical margin status and preoperative PSA. In conclusion, the results of our study demonstrate that expression of FAM13C is an independent prognostic marker in prostate cancer. Finding FAM13C also in non-neoplastic prostate tissues highlights the importance of properly selecting cancer-rich areas for RNA-based FAM13C expression analysis.

Highlights

Prostate cancer is the most prevalent cancer in men in Western society [1]
The results of our study show that FAM13C overexpression is a strong predictor of poor clinical outcome in prostate cancer, and that its prognostic impact is independent of established pathological and clinical parameters
Data on FAM13C expression have never been published in prostate cancer, the gene is a component www.impactjournals.com/oncotarget

Summary

INTRODUCTION

Prostate cancer is the most prevalent cancer in men in Western society [1]. the majority of prostate cancers behave in an indolent manner, a small subset is highly aggressive and requires extensive treatment [2, 3]. Established preoperative prognostic parameters are limited to Gleason grade and tumor extent in biopsies, prostate-specific antigen (PSA), and clinical stage These data are statistically powerful, they are often insufficient for optimal individual treatment decisions. The recent availability of a FAM13C specific antibody facilitates large-scale in-situ analysis in order to clarify whether FAM13C protein expression can serve as a prognostic marker in prostate cancer. Such studies aiming in a systematic analysis of the prognostic value of FAM13C protein expression or its association to cancer phenotype and other molecular features of the disease are lacking. We took advantage of our large prostate cancer prognosis tissue microarray to study FAM13C expression in more than 12,000 individual prostate cancers with pathological and clinical follow-up information

RESULTS

DISCUSSION

MATERIALS AND METHODS