TMEM45B is a novel predictive biomarker for prostate cancer progression and metastasis

Abstract

It is urgently required to explore the clinical relevance of TMEM45B expression and Prostate cancer (PCa), and determine the predictive significance of TMEM45B as a biomarker for PCa patients. Patient-derived xenograft (PDX) models were developed for PCa with different metastatic potential (LTL-418, LTL-313B, LTL-313H and LTL-331). The gene expression microarray of LTL-313H and LTL-313B which derived from a single PCa patient was performed to identify the candidate biomarker gene, TMRM45B. MSKCC and TCGA PCa patient cohorts were introduced to analyze the clinical significance of TMEM45B expression. Quantitative Real-Time PCR (qRT-PCR) revealed that there was a significant increase of TMEM45B expression in the LTL-313H and LTL-331 high metastatic potential tumor lines compared to the LTL-418, LTL-313B low metastatic potential tumor lines. In the MSKCC PCa cohort, the mRNA level of TMEM45B in patients with metastasis was significantly higher than that in primary PCa (p=0.001) and benign prostate hyperplasia patients (BPH) (p<0.001). In addition, the increased TMEM45B expression positively related with higher possibility of biochemical recurrence (p=0.016), distant metastasis (p<0.001) and overall patient survival (p=0.07). Moreover, TMEM45B expression was considered an independent risk factor for metastasis of PCa based on multivariate logistic regression; where Kaplan-Meier analysis showed that patients with elevated TMEM45B had a shorter biochemical recurrence free survival (RFS). In addition, the primary PCa patient subgroup analysis revealed significant association between TMEM45B expression and clinical features, where cases with elevated TMEM45B were more likely to develop metastasis compared to those without it in the N0 primary PCa patient cohort (p=0.010) (Table 3). The primary PCa patient cohort TCGA was used to validate the results, and an obvious relationship was found between TMEM45B and PCa clinical characteristic (T/N stage, Gleason score, Recurrence/Progression). Furthermore, a significant poor disease free survival (DFS) was established in high-level TMEM45B patients compared to those with low levels (p=0.007). The combined results indicate that increased TMEM45B expression appears significantly associated with prostate carcinoma progression and metastasis, and this provides a new prognostic biomarker for predicting metastatic potential in PCa patients; especially those with primary PCa.