Golgi Phosphoprotein 3 Represents a Novel Tumor Marker for Gastric and Colorectal Cancers.

BACKGROUND: Early diagnosis is very important for the clinical treatment of gastric cancer (GC) and colorectal cancer (CRC). We aimed to detect Golgi phosphoprotein 3 (GOLPH3) and evaluate its diagnostic value. MATERIALS AND METHODS: Serum concentrations of GOLPH3 were detected by ELISA in 136 CRC patients, 102 GC patients, and 50 healthy controls at the Second Affiliated Hospital of Fujian Medical University from June 2016 to December 2019. Serum concentrations of CEA and CA19-9 were detected by ECLIA. RESULTS: Serum concentrations of GOLPH3, CEA, and CA19-9 were higher in GC and CRC patients than in healthy controls (P < 0.001). Serum GOLPH3 concentrations were increased in GC and CRC patients with tumors greater than 5 cm, poor differentiation, greater depth of tumor invasion, and increased lymphatic and distant metastases (P < 0.05). In the GC and CRC groups, the AUCs of GOLPH3 were higher than those of CEA and CA19-9 (P < 0.05), while the AUCs of the marker combination were higher than those of GOLPH3 (P < 0.05), and postoperative serum GOLPH3 levels were lower than preoperative levels (P < 0.001). Serum GOLPH3 concentrations in CRC patients correlated positively with CEA and CA19-9 concentrations (P < 0.05). CONCLUSION: Serum GOLPH3 concentrations in GC and CRC patients are related to TNM stage. GOLPH3 may represent a novel biomarker for the diagnosis of GC and CRC. The combination of serum GOLPH3, CEA, and CA19-9 concentrations can improve diagnostic efficiency for GC and CRC. GOLPH3 is expected to become an indicator for the early diagnosis and evaluation of surgical effects.

Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways.

Golgi phosphorylated protein (GOLPH)3 is overexpressed in colorectal cancer tissues and promotes the proliferation of colon cancer cells. A previous study by the authors demonstrated that GOLPH3 was associated with poor prognosis in colorectal cancer. However, the association between GOLPH3 gene overexpression and resistance to platinum-based drugs in colon cancer remains unknown. In the present study, the association between GOLPH3 overexpression and resistance of HT29 colon cancer cells to cisplatin and the mechanism underlying the development of chemoresistance were investigated. HT29 cells were divided into five groups. The expression of GOLPH3 mRNA was measured in the control and siRNA transfection groups. Reverse transcription-quantitative polymerase chain reaction analysis, cell proliferation, colony formation assay, tumor sphere formation and apoptosis (Annexin V) assays, western blotting and a nude mouse tumorigenicity assay were performed. HT29 cells were resistant to 10 µM cisplatin treatment, whereas the expression of GOLPH3, P-glycoprotein, phosphorylated extracellular signal-regulated kinase (pERK)1/2 and ß-catenin protein was significantly upregulated compared with the control group. With cisplatin treatment, silencing GOLPH3 gene expression downregulated the expression of these proteins, reduced cell proliferation and tumorigenicity, induced apoptosis and reversed the resistance of HT29 cells to cisplatin. In addition, the change in pERK1/2 and ß-catenin expression demonstrated that the mechanism of GOLPH3 overexpression involved in cisplatin resistance was associated with activation of the mitogen-activated protein kinase/ERK and Wnt/ß­catenin signaling pathways in HT29 cells. The tumorigenicity experiment in nude mice also demonstrated that silencing GOLPH3 expression increased the sensitivity of HT29 cells to cisplatin in vivo. Therefore, overexpression of GOLPH3 may be involved in the resistance of HT29 colon cancer cells to cisplatin chemotherapy by activating multiple cell signaling pathways.