Profiling Protein Markers Associated with Lymph Node Metastasis in Prostate Cancer by DIGE-based Proteomics Analysis

Abstract

Current predictive tools and imaging modalities are not accurate enough for preoperative diagnosis of lymph node metastatic prostate cancer (LNM PCa). Proteomic analysis is introduced to screen potential biomarkers for early detection of LNM PCa. In our initial study, protein samples from localized and LNM PCa as well as benign prostatic hyperplasia tissues were analyzed using two-dimensional fluorescence difference in gel electrophoresis (2-D DIGE) coupled with MALDI-TOF/TOF MS. We identified 58 proteins that were differentially expressed in the LNM PCa group relative to the localized PCa group. Six of these proteins, e-FABP5, MCCC2, PPA2, Ezrin, SLP2, and SM22, are functionally relevant to cancer metastasis. Expression of these proteins was therefore further validated in tissue samples from the original cohort and also from a larger, independent cohort of patients using real time PCR, Western blotting, and immunohistochemistry staining. In addition, the serum levels of e-FABP5 were also examined by ELISA. Relative to localized PCa tissues, LNM PCa tissues had increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22. Patients with LNM PCa had significantly higher levels of serum e-FABP5. This study presents evidence that increased expression of e-FABP5, MCCC2, PPA2, Ezrin, and SLP2 and decreased expression of SM22 are useful diagnostic markers for the existence of LNM PCa.

Comparative Serum Proteomic Analysis of Serum Diagnosis Proteins of Colorectal Cancer Based on Magnetic Bead Separation and MALDI-TOF Mass Spectrometry

“…Another recent study confirmed the decreased serum levels of apolipoprotein C-1 in CRC (Engwegen et al, 2008). Additionally, protein markers associated with lymph node metastases in colorectal and prostate cancer have been profiled (Pang et al, 2010;Fan et al, 2011).…”

Prostate cancer research in China

“…Six of these protein expression patterns, including the increased expression of e-FABP5, MCCC2, PPA2, Ezrin and SLP2 and the decreased expression of SM22, have a functional relation to PCa progression. 27 HoxB3 was found to promote PCa progression by transactivating CDCA3. 28 CRPC is the result of the regrowth of PCa cells that have adapted to the hormone-deprived environment of the prostate.…”

FABP5 (fatty acid binding protein 5 (psoriasis-associated))

“…Cancer FABP5 is involved in signaling pathways controlling differentiation, metabolism, proliferation, and resistance to apoptosis (Tan et al, 2001) and is highly expressed in several human tumors including breast, prostate, oral, and hepatocellular carcinomas (Adamson et al, 2003;Fujii et al, 2005;Fang et al, 2010). The majority of malignancies associated with elevated FABP5 are of apparent epithelial origin, where FABP5 is believed to contribute to proliferation, metastasis, and resistance to therapy.…”

“…High levels of FABP5 are associated with a poorer prognosis in prostate cancer (Morgan et al, 2008;Forootan et al, 2014). Significantly higher levels of FABP5 protein were found in the serum of patients with lymph node metastatic prostate cancer compared to patients with localized prostate cancer (Pang et al, 2010). As in other cancers, FABP5 appears to influence tumor progression through PPARβ, and levels of both FABP5 and PPARβ correlate with the tumorigenic potential of prostate cancer cell lines by inducing the expression of genes which promote anchorage independence and proliferation (Morgan et al, 2008).…”

“…Overexpression of FABP5 increased invasion, proliferation and production of matrix metalloproteinase-9 (MMP-9) in OSCC cell lines (Fang et al, 2010). Drug-resistant adenocarcinoma of the pancreas is associated with high levels of FABP5, with FABP5 proposed to facilitate the sequestration and removal of cytotoxic drugs in these tumors (Sinha et al, 1999).…”