title: 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.affiliation: Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People's Republic of China. zhulinyang@yahoo.com.
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Xiongying
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Daiqiang
authors.initials: D
authors.lastname: Li
authors.affiliation: Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, 410011, Hunan, People's Republic of China.
authors.forename: Ziru
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zou
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis* / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C491819:FRAT1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins
keywords: ABCG2; Dysplasia; FRAT1; Immunohistochemistry; Pancreatic ductal adenocarcinoma; Pancreatic intraepithelial neoplasia