Glypican-3 and KRT19 are markers associating with metastasis and poor prognosis of pancreatic ductal adenocarcinoma

Article type: Research Article

Authors: Yao, Hongliang^a | Yang, Zhulin^{b; *} | Liu, Ziru^b | Miao, Xiongying^b | Yang, Leping^b | Li, Daiqiang^c | Zou, Qiong^d | Yuan, Yuan^d

Affiliations: [a] Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China | [b] Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, Changsha, Hunan, China | [c] Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China | [d] Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, Hunan, China

Correspondence: [*] Corresponding author: Zhulin Yang, Research Laboratory of Hepatobiliary Diseases, Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha 410011, Hunan, China. Tel.: +86 731 88187376; Fax: +86 731 85295163; E-mail:[email protected]

Abstract: 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.

Keywords: Pancreatic ductal adenocarcinoma, dysplasia, pancreatic intraepithelial neoplasia, GPC3, KRT19, CA19-9, immunohistochemistry

DOI: 10.3233/CBM-160655

Journal: Cancer Biomarkers, vol. 17, no. 4, pp. 397-404, 2016