Increased expression of Golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer

Abstract

BackgroundTo investigate the expression of Golgi phosphoprotein-3 (GOLPH3) in prostate cancer and determine its prognostic value.MethodsImmunohistochemical staining for GOLPH3 was performed on tissue microarrays of 342 prostate patients. The correlation between GOLPH3 expression with its clinicopathologic factors was also analyzed in order to determine its prognostic significance.ResultsGOLPH3 expression of normal prostate tissues, benign prostate hyperplasia, high-grade prostatic intraepithelial neoplasia, and hormone-dependent prostate cancer (HDPC) did not show any statistically significant difference. In contrast, statistically significant difference was reported in moderate/intense GOLPH3 expression in cases diagnosed with HDPC and castration resistant prostate cancer (CRPC) (P < 0.0005). Moderate /intense expression of GOLPH3 was associated with androgen independence (P = 0.012), higher Gleason score (P = 0.017), bone metastasis (P = 0.024), higher baseline prostate-specific antigen (PSA) (P = 0.038), and higher PSA nadir (P = 0.032). A significantly negative correlation was found between moderate/intense GOLPH3 expression and disease-free survival (DFS) (HR = 0.28, P = 0.012) and overall survival (OS) (HR = 0.42, P = 0.027). Univariated analysis indicated that moderate/intense GOLPH3 expression created a significantly prognostic impact in patients with CRPC. On the other hand, multivariate analysis indicated that GOLPH3 was a significantly independent prognostic factor of DFS (P = 0.027) in all prostate cancer patients.ConclusionsIn this study, it was discovered that the overexpression of GOLPH3 is associated with the transition of prostate cancer from hormone sensitive phase to hormone refractory phase. GOLPH3 might be an important prognostic factor of DFS and OS in patients with prostate cancer. In totality, GOLPH3 could be used as a novel candidate in devising a more effective therapeutic strategy to tackle CRPC.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1452541171722856.

Functional Heterogeneity of Cancer-Associated Fibroblasts from Human Colon Tumors Shows Specific Prognostic Gene Expression Signature

“…Surprisingly, differences in pathways relating to "protein targeting to Golgi" between CAF subtypes were observed. In line with the data presented, recent studies have shown that overexpression of Golgi proteins, such as Golgi phosphoprotein 3 in cancer cells, correlated with their proliferation and tumorigenicity in vitro (35)(36)(37)(38)(39). In addition, descriptions of the molecular network, connecting the Golgi to other organelles, demonstrate the essential roles of the Golgi in different cellular activities, indicating their possible role in prostate tumors (40).…”

Phosphatidylinositol 4-Phosphate in the Golgi Apparatus Regulates Cell–Cell Adhesion and Invasive Cell Migration in Human Breast Cancer

“…For example, GOLPH3 upregulated and promotes proliferation and tumorigenicity in breast cancer (15). Recent studies have demonstrated the clinical significance of GOLPH3 in several cancers (13,14,43). A very recent study reported that GOLPH3 contributes to the migration and invasion of glioma cells through RhoA expression (44).…”

“…Recently, GOLPH3 was shown to be involved in cancer progression. Human chromosome 5p13, on which the GOLPH3 gene is located, is amplified in several cancers (10), and expression of GOLPH3 is increased in several cancer cell lines and in some patients with cancer (11)(12)(13)(14). GOLPH3 enhances cell proliferation and tumorigenicity (10,15).…”

Mitochondria “fuel” breast cancer metabolism: Fifteen markers of mitochondrial biogenesis label epithelial cancer cells, but are excluded from adjacent stromal cells

“…For example, GOLPH3, which is a marker of increased mitochondrial lipid synthesis, has already been shown to predict poor clinical outcome in oral, esophageal and prostate cancers as well as glioblastomas. [49][50][51][52] Similarly, we have recently demonstrated that overexpression of GOLPH3 in the triple-negative breast cancer cell line, MDA-MB-231 cells, increases mitochondrial function and promotes tumor growth, without a significant increase in tumor angiogenesis.…”