High Golgi Phosphoprotein 3 Expression Research Articles

Comparative analysis of GOLPH3 expression in lymph node-positive prostate cancer: immunohistochemistry staining patterns and clinical significance.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression. The study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed. A positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP - the higher the expression of GOLPH3, the lower the efficacy of RP was (p<0.05). GOLPH3 is expressed in both prostate and metastatic lymph nodes, with higher expression in metastatic lymph nodes. High GOLPH3 expression was associated with the occurrence of LVI, higher-risk group in the EAU classification, and lower efficacy of the RP, but there was no significant correlation with other pathological features or postoperative outcomes.

Golgi phosphoprotein-3 (GOLPH3) promote metastasis of nasopharyngeal carcinoma through regulating E-cadherin.

The purpose of this study was to investigate GOLPH3 expression in nasopharyngeal carcinoma (NPC) and its influence on the metastatic ability of NPC cells; meanwhile, the underlying mechanism of GOLPH3 promoting the malignant progression of NPC was also explored. In this study, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression of GOLPH3 in 34 pairs of tumor tissue and paracancerous tissue specimens collected from NPC patients, and the interplay between GOLPH3 expression and clinical indicators was analyzed, as well as the prognosis of NPC patients. Meanwhile, GOLPH3 expression in NPC cell lines was further verified by qRT-PCR assay. Furthermore, GOLPH3 knockdown model was constructed in NPC cell lines, including SUNE2 and CNE. Then, cell counting kit-8 (CCK-8), transwell invasion, and cell wound healing assays were applied to analyze the effect of GOLPH3 on the biological function of NPC cells. In addition, an in-depth study of the relationship between GOLPH3 and E-cadherin was conducted. QRT-PCR results indicated that the expression level of GOLPH3 in NPC was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with patients with low expression of GOLPH3, those with high expression of GOLPH3 had a higher incidence of lymph node metastasis. Compared with sh-NC group, the proliferation and invasive ability of NPC cells decreased remarkably after knockdown of GOLPH3. Subsequently, E-cadherin expression was found to be remarkably reduced and negatively correlated with GOLPH3 in NPC cell lines and tissues. Finally, the recovery experiment demonstrated that GOLPH3 might have a mutual regulatory relation with E-cadherin, both of which jointly affect the malignant progression of NPC. GOLPH3 expression is remarkably associated with lymph node metastasis and poor prognosis of NPC patients; in addition, it may promote the proliferation and metastatic ability of NPC cells by regulating E-cadherin.

Expression of GOLPH3 in patients with non-small cell lung cancer and xenografts models.

Increased expression of Golgi phosphoprotein 3 (GOLPH3) has been reported to be associated with several types of human cancer. Patient-derived cancer xenograft models have demonstrated great potential in preclinical studies. In the present study, the link between GOLPH3 expression and survival was examined in patients with non-small cell lung cancer (NSCLC). Patient-derived lung cancer xenograft models were established with two different methods. Lastly, the association between GOLPH3 expression and establishment of the xenograft models was explored. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry analysis were used to examine GOLPH3 expression in 60 NSCLC tissues and matched adjacent non-cancerous tissues (ANT). In addition, tumor pieces from the 60 NSCLC tissues were implanted in the subcutaneous layer and in the subrenal kidney capsule of nude mice. RT-qPCR, histopathology and immunohistochemistry were used to confirm the human origin of the xenograft tumors. RT-qPCR was also used to research the mutation status of GOLPH3 in the xenograft tumors. The results demonstrated that NSCLC tissues had higher expression of GOLPH3, at the mRNA and protein level, compared with ANT. High expression of GOLPH3 correlated with poor survival in patients with NSCLC. Successful engraftment was established for 27 tissues in the subrenal kidney capsule and for 16 in the subcutaneous layer of nude mice. The subrenal kidney capsule group demonstrated significantly higher engraftment rates than the subcutaneous layer group. In addition, higher GOLPH3 expression in the tumor tissues was significantly correlated with higher engraftment rates in mice. In both groups, few xenografts lost the GOLPH3 mutation. In summary, GOLPH3 may be an important diagnosis and prognosis indicator in patients with NSCLC. The genotype and phenotype of the xenograft tumors derived from patient lung cancer tissues exhibited significant similarities to the originating primary tumors. High GOLPH3 expression may promote the successful establishment of xenograft models for NSCLC.

GOLPH3: a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

The association between Golgi phosphoprotein 3 (GOLPH3) and clinical pathological characteristics, as well as the clinical outcomes of both neoadjuvant and adjuvant chemotherapies in breast cancer, remain largely unknown. In this study, we investigated the biological role and clinical significance of GOLPH3 in breast cancer. We found that GOLPH3 expression in tumor tissue was higher than that in adjacent noncancerous tissue (ANT) and fibroadenoma. GOLPH3 silencing reduced the migration, invasion, and proliferation of breast cancer cells and promoted apoptosis of the cells. Importantly, patients with high GOLPH3 expression had worse disease-free survival (DFS) and overall survival (OS), and GOLPH3 expression was correlated with clinical pathological characteristics such as molecular subtype, tumor-node-metastasis classification, and age but was not associated with surgery type. Patients with high GOLPH3 expression had poor DFS and OS in every molecular subtype, and an increase in tumor invasion and lymph node metastasis. The risk of recurrence increased with age in patients with high GOLPH3 expression, and surgery type had no influence on patient survival. This is the first study to investigate the correlation between GOLPH3 and response to chemotherapy in breast cancer. Patients with high GOLPH3 expression showed resistance to neoadjuvant and adjuvant chemotherapies, and GOLPH3 overexpression indicated a high risk of recurrence in patients who received adjuvant chemotherapy. These data suggest that GOLPH3 may be a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

GOLPH3 overexpression correlates with poor response to neoadjuvant therapy and prognosis in locally advanced rectal cancer

Neoadjuvant chemoradiotherapy (nCRT) combined with surgery is a standard therapy for locally advanced rectal cancer (LARC). The aim of this study was to assess the expression of GOLPH3 (Golgi phosphoprotein 3), a newly found oncogene, in LARC as well as its relationship with nCRT sensitivity and prognosis. We retrospectively analyzed 148 LARC cases receiving nCRT and total mesorectal excision (TME). Immunohistochemistry was used to assess GOLPH3 and mTOR (mammalian target of rapamycin) in tumor tissues. Then, the associations of GOLPH3 with pathological characteristics and prognosis of rectal cancer were assessed. The 148 cases included 77 with high GOLPH3 expression (52.03%), which was associated with tumor invasive depth and lymphatic metastasis. Cases with high GOLPH3 expression had 2.58 and 2.71 fold higher local relapse and distant metastasis rates compared with the low expression group. Correlation analyses showed that GOLPH3 was an independent indicator for judging tumor down-staging and postoperative TRG (tumor regression grade), indicating it could predict nCRT sensitivity. In addition, GOLPH3 expression was associated with mTOR levels. Multiple-factor analysis indicated that GOLPH3 was an independent prognosis indicator for 5 year-DFS (disease free survival) and OS (overall survival) in LARC. These results reveal that GOLPH3 is an independent predictive factor for nCRT sensitivity and prognosis in LARC, with a mechanism related to mTOR.

Letter of Retraction

It has come to our attention that the a manuscript published in CIM: JianXin J, Cha Y, ZhiPeng L, Jie X, Hao Z, Meiyuan C, ChengYi S "GOLP3 is a predictor of survival in patients with hepatocellular carcinoma" Clin Invest Med. 2014 Aug 1;37(4):E233-42 contains text identical to a manuscript published in Tumour Biology: Hu GS, Li YQ, Yang YM, Shi W, Liao AJ, Yao YH, Zeng B, Yuan J "High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma" Tumour Biol. 2014 Sep;35(9):8625-32. doi: 10.1007/s13277-014-2105-8. Epub 2014 May 28. For this reason, the publication in CIM has been retracted. Jonathan Angel, MD Editor, CIM.

High GOLPH3 expression is associated with poor prognosis and invasion of hepatocellular carcinoma.

Golgi phosphoprotein3 (GOLPH3) overexpression has previously been associated with the progression of several solid tumors, which resulted in adverse clinical outcomes. The present study aimed to determine the expression and prognostic significance of GOLPH3 in human hepatocellular carcinoma (HCC). GOLPH3 expression was examined using western blot analysis of 30 paired samples of HCC and adjacent non‑cancerous liver tissues. GOLPH3 expression levels were also assessed using immunohistochemistry in 180 HCC samples and paired controls. In addition, the association of GOLPH3 expression with clinicopathological features and clinical outcome was analyzed. Furthermore, the effect of GOLPH3 on HCC cell proliferation and invasion were determined. Western blot analysis revealed that GOLPH3 expression was significantly elevated in HCC tissue compared with that of the matched adjacent non‑cancerous liver tissue. In addition, the results of the immunohistochemical analysis demonstrated that GOLPH3 expression was positively correlated with the Edmondson‑Steiner grade (P=0.006), vascular invasion (P=0.002) and serum αfeto‑protein levels (P=0.015). GOLPH3 expression was found to be an independent factor for predicting the poor overall survival of HCC patients (hazard ratio, 2.01; 95% confidence interval, 1.26‑3.64; P=0.025). In addition, GOLPH3 silencing inhibited the proliferation, invasion and migration of HCC cell lines invitro. In conclusion, the results of the present study demonstrated that high GOLPH3 levels may be a potential biomarker for the poor prognosis of patients with HCC.

Overexpression of GOLPH3 is associated with poor prognosis and clinical progression in pancreatic ductal adenocarcinoma.

BackgroundGolgi phosphoprotein 3 (GOLPH3) has been identified as an oncoprotein in various human cancers; however, its role in pancreatic ductal adenocarcinoma (PDAC) is unknown. We examined GOLPH3 expression levels and relationship with survival in patients with PDAC to establish the significance of GOLPH3 in the development and progression of PDAC.MethodsReal-time qPCR and Western blotting were performed to analyze the expression levels of GOLPH3 mRNA and protein in paired PDAC tumor and adjacent non-tumor tissues. Immunohistochemistry was used to analyze the expression levels of GOLPH3 protein in paraffin-embedded tissues from 109 cases of PDAC. Univariate and multivariate analyses were performed to identify correlations between the immunohistochemical data for GOLPH3 expression and the clinicopathologic characteristics in PDAC.ResultsExpression levels of GOLPH3 mRNA and protein were upregulated in PDAC lesions compared to paired adjacent noncancerous tissues. Expression of GOLPH3 was significantly correlated with clinical stage (P = 0.006), T classification (P = 0.021), N classification (P = 0.049) and liver metastasis (P = 0.035). Patients with high GOLPH3 expression had shorter overall survival times compared to those with low GOLPH3 expression (P = 0.007). Multivariate analysis revealed that GOLPH3 overexpression was an independent prognostic factor in PDAC.ConclusionsOur findings suggest that GOLPH3 expression status may be a potential prognostic biomarker and therapeutic target in PCAC.

High expression of Golgi phosphoprotein-3 is associated with poor survival in patients with hepatocellular carcinoma

Golgi phosphoprotein 3 (GOLPH3) is recently demonstrated to function as an oncogene involved in the development and progression of cancers. However, little is known about GOLPH3 expression and its clinical significance in hepatocellular carcinoma (HCC). The levels of GOLPH3 messenger RNA (mRNA) and protein in HCC cell lines and fresh tissues were determined by quantitative RT-PCR and western blotting. Additionally, the protein expression of GOLPH3 was detected in 167 paraffin-embedded HCC samples by immunohistochemistry. GOLPH3 mRNA and protein was overexpressed in HCC cell lines and tissues than the immortalized normal hepatocyte cell line LO2 and the adjacent nontumorous live tissues, respectively. High GOLPH3 expression was positively correlated with high serum AFP level (P = 0.015) and more tumor recurrence or metastasis (P = 0.010). In addition, HCC patients with high GOLPH3 expression had poorer overall survival (hazard ratio (HR), 1.87; 95 % confidence interval (CI), 1.19-2.94; P = 0.006) and poorer disease-free survival (HR, 1.90; 95 % CI, 1.21-2.98; P = 0.005) than those with low GOLPH3 expression. The cumulative 5-year survival rate was only 35.19 % (95 % CI, 26.18-44.20 %) in the high GOLPH3 expression group, whereas it was 55.93 % (95 % CI, 43.26-68.60 %) in the low GOLPH3 expression group. Furthermore, multivariate Cox regression analysis demonstrated that the expression of GOLPH3, tumor size, and tumor multiplicity were independent prognostic predictors for HCC patients. GOLPH3 was overexpressed in HCC at both the mRNA and protein levels, and high expression of GOLPH3 could be served as a novel and potential prognostic biomarker for HCC patients.

High Expression of GOLPH3 in Esophageal Squamous Cell Carcinoma Correlates with Poor Prognosis

BackgroundWhether the expression of Golgi phosphoprotein 3 (GOLPH3) correlates with esophageal cancer tumorigenesis is currently unclear. The aim of this study was to examine GOLPH3 expression in patients with esophageal squamous cell cancer (ESCC) and explore its clinical significance.MethodsDifferences in the expression of GOLPH3 at the mRNA and protein level were examined via quantitative reverse transcriptase PCR and western blotting, respectively. GOLPH3 expression levels in ESCC tissue were determined through immunohistochemistry, and were compared in accordance with specific clinicopathological features of the patients and tissue specimens. Factors associated with patient survival were also analyzed.ResultsA notably higher level of GOLPH3 expression was found in ESCC cell lines and tissues at both mRNA and protein levels. High expression of GOLPH3 in ESCC patients was positively associated with clinical stage, TNM classification, histological differentiation and vital status (all P<0.0001). Expression of GOLPH3 was found to be an independent prognostic factor in ESCC patients. ESCC patients expressing high levels of GOLPH3 exhibited a substantially lower 5-year overall survival than GOLPH3-negative patients. Furthermore, a significant correlation between high GOLPH3 expression and shorter overall survival time was found in different subgroups of ESCC patients stratified by the clinical stage, T classification, and lymph node metastasis.ConclusionsExperiments demonstrated potential involvement of GOLPH3 in the development, differentiation, and tumorigenesis of ESCC, and concludes the possibility of its use as a diagnostic and prognostic marker in patients with ESCC.

Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis

Golgi phosphoprotein-3 (GOLPH3), an important protein in mammalian target of rapamycin (mTOR) signaling, is overexpressed in and correlates with the pathological grade of glioma. However, the potential correlation between GOLPH3 and clinical outcome in patients with glioblastoma multiforme (GBM) remains unknown. In this study, we examined GOLPH3 expression in GBM by tissue microarray and correlated this measure to patient outcome. GOLPH3 expression in tumor tissue from 97 primary GBM patients was examined by tissue microarray and immunohistochemistry. Potential effects of GOLPH3 on tumor growth were also examined in representative cell lines (U251 and U87) by downregulating GOLPH3 with RNA interference. For this cohort, the median overall survival (OS) was 12 months [95 % confidence interval (CI): 10.31-13.69 months], and the median progression-free survival (PFS) was 10 months (95 % CI: 7.33-12.67 months). Tissue microarray analysis revealed high GOLPH3 expression in 40 patients (40/97, 41.2 %) and low GOLPH3 expression in the remaining 57 patients (57/97, 58.8 %). Log-rank test showed that patients with low GOLPH3 expression had significantly longer median OS (15 versus 10 months in patients with high GOLPH3 expression, p = 0.009) and median PFS (12 versus 7 months, p = 0.015). Univariate and Cox analysis indicated that GOLPH3 was an independent prognostic factor for OS and PFS. In in vitro experiments, GOLPH3 downregulation by small interfering RNA (siRNA) suppressed proliferation and clonogenic growth in cultured cell lines. These findings demonstrate that high GOLPH3 expression is associated with poor outcome of GBM patients.

Overexpression of GOLPH3 Promotes Proliferation and Tumorigenicity in Breast Cancer via Suppression of the FOXO1 Transcription Factor

Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in various biologic processes. The clinical significance and biologic role of GOLPH3 in breast cancer, however, remains unknown. Expression of GOLPH3 in normal breast cells, breast cancer cells, and 6-paired breast cancer and adjacent noncancerous tissues were quantified using real-time PCR and Western blotting. GOLPH3 protein expression was analyzed in 258 archived, paraffin-embedded breast cancer samples using immunohistochemistry. The role of GOLPH3 in breast cancer cell proliferation and tumorigenicity was explored in vitro and in vivo. Western blotting and luciferase reporter analyses were used to investigate the effect of GOLPH3 overexpression and silencing on the expression of cell-cycle regulators and FOXO1 transcriptional activity. GOLPH3 was significantly upregulated in breast cancer cells and tissues compared with normal cells and tissues. Immunohistochemical analysis revealed high expression of GOLPH3 in 133 of 258 (51.6%) breast cancer specimens. Statistical analysis showed a significant correlation of GOLPH3 expression with advanced clinical stage and poorer survival. Overexpression and ablation of GOLPH3 promoted and inhibited, respectively, the proliferation and tumorigenicity of breast cancer cells in vitro and in vivo. GOLPH3 overexpression enhanced AKT activity and decreased FOXO1 transcriptional activity, downregulated cyclin-dependent kinase (CDK) inhibitor p21(Cip1), p27(Kip1), and p57(Kip2), and upregulated the CDK regulator cyclin D1. Our results suggest that high GOLPH3 expression is associated with poor overall survival in patients with breast cancer and that GOLPH3 overexpression increases the proliferation and tumorigenicity of human breast cancer cells.