High GOLPH3 expression is associated with a more aggressive behavior of epithelial ovarian carcinoma

Abstract

Overexpression of GOLPH3 (Golgi phosphoprotein 3, 34 kDa) is associated with the progression of many solid tumor types leading to an unfavorable clinical outcome. The present study examined the association between GOLPH3 expression and tumor development, clinicopathological factors, and prognosis of epithelial ovarian carcinoma. GOLPH3 expression was examined by immunohistochemistry in 18 normal ovarian samples, 28 benign tumors, 55 serous borderline ovarian tumors, and 135 epithelial ovarian carcinomas. The association of GOLPH3 expression with clinical characteristics, response to chemotherapy, and overall survival of epithelial ovarian carcinoma patients was analyzed on fresh tissue samples. GOLPH3 mRNA and protein expression in ovarian cancer and normal ovarian tissues were detected by real-time quantitative RT-PCR and Western blotting, respectively. The results are the following: (1) GOLPH3 immunostaining localized to the cytoplasm in two patterns, condensed into large granules with perinuclear distribution, and dispersed in the cytoplasm as fine granules. (2) GOLPH3 expression was higher in epithelial ovarian carcinoma than in normal ovarian tissues at the mRNA and protein level. The frequency of high-level expression of GOLPH3 increased progressively from benign (cystadenoma) to borderline neoplasms to malignant lesions. (3) Dispersed cytoplasmic GOLPH3 expression in epithelial ovarian carcinoma patients was highly correlated with FIGO stage (p < 0.001), tumor histological grade (p = 0.003), lymph node involvement (p = 0.001), and chemotherapy response (p = 0.034). (4) A dispersed pattern of GOLPH3 expression was an independent prognostic factor for poor overall survival. Patients with low dispersed cytoplasmic GOLPH3 expression had significantly longer overall survival than patients with high dispersed cytoplasmic expression. In contrast, GOLPH3 condensed expression was not correlated with clinicopathological features, chemotherapy response, or prognosis. GOLPH3 gene expression might play a role in tumorigenesis in epithelial ovarian carcinoma as upregulation of GOLPH3 expression is associated with a more aggressive tumor phenotype. GOLPH3 immunohistochemistry may be of value to predict the outcome of ovarian carcinoma patients.

GOLPH3 high expression predicts poor prognosis in patients with resected non-small cell lung cancer: an immunohistochemical analysis

“…Moreover, DFS of patients with NSCLC and high GOLPH3 overexpression was poorer compared with that of patients with NSCLC and low GOLPH3 expression. Subsequently, we found that GOLPH3 expression in NSCLC was notably Previous studies revealed that GOLPH3 is closely related to the occurrence and development of malignant solid tumours, such as renal, ovarian, breast, and oesophageal cancers [17][18][19][20]. To our knowledge, this study is the first to indicate an association between GOLPH3 positivity in patients with NSCLC and poor prognosis and to suggest that GOLPH3 expression may be an independent prognostic factor for patients with NSCLC.…”

Oncogenic Roles of GOLPH3 in the Physiopathology of Cancer

“…An increasing number of papers has shown that GOLPH3 drives cancer in several other solid tumors such as Neuroblastoma (NB) [42], Non-Small Cell Lung Cancer (NSLC) [89], epithelial ovarian carcinoma [90], prostate cancer [91,92], gastric cancer [93], and hepatocellular carcinoma [94,95] ( Figure 2). Recent reports indicate that GOLPH3 overexpression can be used as a positive biomarker for tumor progression and poor survival in these cancer types [89][90][91][92][93][94][95][96][97][98]. Experimental data in cancer cell lines or in nude mice revealed the role of GOLPH3 in cell proliferation, metastasis formation and angiogenesis ( Figure 2).…”

Mechanisms of GOLPH3 Associated with the Progression of Gastric Cancer: A Preliminary Study

“…This protein localizes to the cytoplasmic face of the trans-Golgi and has been closely associated with tumorigenicity [3] , [8] . Large studies have found that GOLPH3 overexpression occurs in several human cancers, including epithelial ovarian carcinoma, renal cell carcinoma, glioblastoma multiforme, esophageal squamous cell carcinoma, and oral tongue cancer [12] – [16] . Evidence suggests that GOLPH3 is involved in tumorigenesis and correlates with poor prognosis.…”