Abstract 5151: Integrative genomic analysis identifies cancer-testis antigen LEMD1 as a prognostic biomarker.

The ability to molecularly distinguish disease states can improve prognostic resolution and therapeutic options. Cancer-testis antigens (CTA), expressed in germ cells of the testis and in a variety of cancers, are of particular interest for their potential use as targets for anti-cancer vaccines. We highlight the application of the NextBio platform, which integrates multiple datatypes such as RNA/miRNA expression, copy number variation, epigenetic changes, and next-generation sequencing with clinical attributes to identify and characterize novel disease associations in multiple myeloma. Genomic and clinical data of 2,546 multiple myeloma patients obtained from public data sources were investigated in the NextBio platform. We initially analyzed the gene expression of various clinical subgroups to the median expression of all groups to identify genes significantly correlated to patient survival. We filtered for patients with advanced disease, defined as those with beta-2 microglobulin blood levels greater than 5.5mg/L, and identified LEMD1, a CTA, as positively correlated with survival (p=2.3E-6). We then analyzed the gene expression of LEMD1 in patients of all disease stages, and found those with increased expression of LEMD1 had improved survival compared to those who did not (p=9.4E-3). Patients with increased expression of LEMD1, however, had concomitant decreased expression in 14/20 CTAs of the MAGE family (p A preliminary exploration of LEMD1 expression in other cancers found increased expression of LEMD1 to be significantly associated with improved survival in ovarian cancer (p=5.4E-3) but reduced survival in renal cancer (p=0.01). Further analysis of LEMD1 expression in normal tissues showed high expression of LEMD1 in spermatozoa and limited expression in 315 other tissue and cell types. As tissue specific antigens behind the blood-testis barrier, the expression of CTAs in cancer can potentially serve as immunogenic targets, and further investigation is warranted to explore their use in tumor immunotherapy. Citation Format: Jenny Park, Beatrice Chiu, Joe Delaney, Cate Paschal, Daniel Roche, James Shima, Anita Umesh, Robert Wisotzkey, Mamatha Shekar, Ilya Kupershmidt. Integrative genomic analysis identifies cancer-testis antigen LEMD1 as a prognostic biomarker. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5151. doi:10.1158/1538-7445.AM2013-5151