Glypican-3 and KRT19 are markers associating with metastasis and poor prognosis of pancreatic ductal adenocarcinoma.
OBJECTIVE
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor with metastasis in most patients at diagnosis. The molecular mechanisms associated with its high malignancy have not been fully elucidated. This study investigated the clinicopathological significances of GPC3 and KRT19 expression in PDAC.


METHODS
GPC3, KRT19, and CA19-9 protein expression were measured by immunohistochemistry.


RESULTS
GPC3 and KRT19 protein levels were overexpressed in PDAC tumors compared to normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P< 0.01). The percentage of positive GPC3 and KRT19 expression were significantly higher in PDAC patients with larger tumor size, poorly differentiated tumor, lymph node metastasis, invasion, and TNM stage III/IV disease than in patients with small tumor size, well-differentiated tumor, no lymph node metastasis and invasion, as well as TNM stage I/II stage disease (P< 0.05 or P< 0.01). Benign pancreatic lesions with positive GPC3 and KRT19 protein expression exhibited dysplasia or intraepithelial neoplasia. Kaplan-Meier survival analysis showed that PDAC patients with positive GPC3 and KRT19 expression survived significantly shorter than patients with negative GPC3 and KRT19 expression (P < 0.05 or P< 0.001). Cox multivariate analysis revealed that positive GPC3 and KRT19 expression were independent poor prognosis factors in PDAC patients.


CONCLUSIONS
GPC3 and KRT19 overexpression are associated with carcinogenesis, progression, and poor prognosis in patients with PDAC and a valuable biomarker for diagnosis of PDAC.
Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hongliang
H
Yao
Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhulin
Z
Yang
Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ziru
Z
Liu
Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiongying
X
Miao
Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Leping
L
Yang
Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Daiqiang
D
Li
Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Qiong
Q
Zou
Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yuan
Y
Yuan
D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D053673:Glypicans / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis
D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D053539:Keratin-19
CA19-9; GPC3; KRT19; Pancreatic ductal adenocarcinoma; dysplasia; immunohistochemistry; pancreatic intraepithelial neoplasia