Abstract 4344: Olfactomedin 4 plays a tumor-suppressor role and is a novel candidate biomarker in the prostate cancer progression and independent of PSA

Abstract

Abstract Prostate cancer is the most commonly diagnosed solid tumor and the second leading cause of cancer-related death in the American male population. The olfactomedin 4 gene (OLFM4) plays critical tumor suppressor roles in human and murine prostate cancer. We have previously reported that loss or reduce of OLFM4 expression is associated with the progression of human prostate cancer. We further found that loss of Olfm4 leads to prostate neoplastic progression in the Olfm4-knockout mouse model. To study the clinical impacts of OLFM4 gene in the prostate cancer, we have performed bioinformatics analysis from the published datasets, GSE35988, GSE21032 and TCGA as well as immunohistochemical analysis with prostate cancer tissue arrays by using OLFM4 antibody. The copy number variations (CNV) of OLFM4 gene were significantly associated with Gleason scores of prostate cancer. The pattern of OLFM4 CNV is similar with other tumor suppressor genes, RB1, PTEN and P53. We have observed consist reduce or loss of mRNA expression in the castrate resistant and metastatic prostate cancer patient samples. To study the relationship between OLFM4 expression and prostate cancer recurrence, we performed Kaplan-Meier Plots and Log-rank statistic analysis for GSE21032 and TCGA data sets. Overall, there was no significant relationship between OLFM4 expression and prostate cancer recurrence. However, when analysis was restricted to the lower quartile of OLFM4 expression, we obtained a highly significant inverse relationship (p = 0.02) between OLFM4 expression and recurrence. We also observed that alteration of CNV and expression of OLFM4 gene has no relationship with the level of (patient) serum prostate specific antigen (PSA). We performed immunohistochemical analysis with prostate cancer tissue arrays by using OLFM4, PSA and E-cadherin antibodies. Lower or loss of expression of OLFM4 protein is associated with advanced Gleason scores of prostate cancer specimens. The pattern of OLFM4 protein expression in prostate cancer patient samples is similar to that of E-cadherin, but not PSA. Taken together, these results suggest that OLFM4 plays a tumor-suppressor role, and therefore is a likely therapeutic target for prostate cancer interdiction. Citation Format: Hongzhen Li, Ye Chen, Wenli Liu, Jianqiong Zhu, Chin Kay, Xujing Wang, Griffin P. Rodgers. Olfactomedin 4 plays a tumor-suppressor role and is a novel candidate biomarker in the prostate cancer progression and independent of PSA. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4344. doi:10.1158/1538-7445.AM2015-4344