The clinical significance of FRAT1 and ABCG2 expression in pancreatic ductal adenocarcinoma.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with intrinsic resistance to cytotoxic agents. The molecular mechanisms associated with high malignancy and resistance to chemotherapy and radiotherapy have not been fully elucidated. This study investigated the clinicopathological significances of frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) and ATP-binding cassette subfamily G member 2 (ABCG2) expression in PDAC. FRAT1 and ABCG2 protein expression in 106 PDAC, 35 peritumoral tissues, 55 benign pancreatic tissues, and 13 normal pancreatic tissues was measured by immunohistochemistry. FRAT1 and ABCG2 protein was overexpressed in PDAC tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P < 0.01). The percentage of cases with positive FRAT1 and ABCG2 overexpression was significantly higher in PDAC patients with poor differentiation, lymph node metastasis, invasion, and TNM stage III/IV disease than in patients with well-differentiated tumor, no lymph node metastasis and invasion, and TNM stage I/II disease (P < 0.05 or P < 0.01). In pancreatic tissues with benign lesions, tissues with positive FRAT1 and ABCG2 protein expression exhibited dysplasia or intraepithelial neoplasia. Kaplan-Meier survival analysis showed that PDAC patients with positive FRAT1 and ABCG2 expression survived significantly shorter than patients with negative FRAT1 and ABCG2 expression (P < 0.05 or P < 0.001). Cox multivariate analysis revealed that positive FRAT1 and ABCG2 expression was an independent poor prognosis factor in PDAC patients. FRAT1 and ABCG2 overexpression is associated with carcinogenesis, progression, and poor prognosis in patients with PDAC.

• Authors: Yuan Yuan, Zhulin Yang, Xiongying Miao, Daiqiang Li, Ziru Liu, Qiong Zou
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 36 Issue 12 Pg. 9961-8 (Dec 2015) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26178481 (Publication Type: Journal Article)

Chemical References

• ABCG2 protein, human
• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters
• Adaptor Proteins, Signal Transducing
• Biomarkers, Tumor
• FRAT1 protein, human
• Intracellular Signaling Peptides and Proteins
• Neoplasm Proteins
• Proto-Oncogene Proteins

Topics

• ATP Binding Cassette Transporter, Subfamily G, Member 2
• ATP-Binding Cassette Transporters (biosynthesis, genetics)
• Adaptor Proteins, Signal Transducing
• Adenocarcinoma (genetics, pathology)
• Aged
• Biomarkers, Tumor (biosynthesis, genetics)
• Carcinoma, Pancreatic Ductal (genetics, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Intracellular Signaling Peptides and Proteins (biosynthesis, genetics)
• Kaplan-Meier Estimate
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Proteins (biosynthesis, genetics)
• Neoplasm Staging
• Prognosis
• Proto-Oncogene Proteins (biosynthesis, genetics)