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Zhai L.-L.,Anhui Medical University | Zhai L.-L.,Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery | Cai C.-Y.,Anhui Medical University | Wu Y.,Anhui Medical University | And 2 more authors.
International Journal of Clinical and Experimental Pathology | Year: 2015

Aberrant expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 not only correlate with tumorigenesis, but also with tumor invasion and metastasis. This study aims to investigate the correlation and prognostic significance of MMP-2 and TFPI-2 differential expression in pancreatic carcinoma. Immunohistochemistry was used to evaluate MMP-2 and TFPI-2 expression in tumor tissues and corresponding non-tumor tissues from 122 patients with pancreatic carcinoma. The results showed that the expression of MMP-2 was significantly (P < 0.05) higher in tumor tissues (78.7%) than in adjacent non-tumor tissues (27.9%), whereas the expression of TFPI-2 was significantly (P < 0.001) lower in tumor tissues (27.9%) than in adjacent non-tumor tissues (79.5%). Spearman's rank correlation test showed a negative correlation between MMP-2 and TFPI-2 expression (r = -0.346, P < 0.001). Kaplan-Meier survival analysis showed that high MMP-2 expression was significantly correlated with decreased disease-free survival (DFS) (P < 0.001) and overall survival (OS) (P < 0.001), while high TFPI-2 expression was significantly associated with increased DFS (P < 0.001) and OS (P < 0.001) of the patients. Multivariate analysis showed that high MMP-2 expression can act as an independent predictive factor for poor DFS (P = 0.01); and low TFPI-2 expression as an independent prognostic factor for poor DFS (P < 0.001) and OS (P < 0.001). In conclusion, our findings suggested that the differential expression of MMP-2 and TFPI-2 have a negative correlation in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for prognosis of pancreatic carcinoma.


Chen J.,Anhui Medical University | Chen J.,Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery | Xu H.,Anhui Medical University | Xu H.,Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery | And 2 more authors.
Therapeutics and Clinical Risk Management | Year: 2016

Soluble major histocompatibility complex class I-related chain A molecules (sMICA) and natural-killer group 2 member D (NKG2D) not only correlate with tumorigenesis and progression, but also with tumor invasion and metastasis. In this study, we used immunohistochemistry to investigate the correlation and prognostic significance of the differential expression of sMICA and NKG2D in pancreatic carcinoma and paracarcinoma tissues from 70 patients with pancreatic carcinomas. The results showed that sMICA expression was significantly (P<0.05) higher in tumor tissues (67.1%) than that in adjacent nontumor tissues (31.4%), whereas NKG2D expression was significantly (P<0.001) lower in tumor tissues (32.9%) than that in adjacent nontumor tissues (60.0%). Spearman’s rank correlation test showed a negative correlation between the expression of sMICA and that of NKG2D (r=-0.676, P<0.001). Kaplan–Meier survival analysis showed that a high sMICA expression was significantly correlated with decreased disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001), while a high NKG2D expression was significantly associated with increased DFS (P=0.001) and OS (P=0.001) of the patients. Multivariate analysis showed that a high sMICA expression was an independent predictive factor for poor DFS (P<0.001) and OS (P=0.012); but low NKG2D expression was not an independent prognostic factor for poor DFS (P=0.238) and OS (P=0.574). In conclusion, our findings suggest that the expression levels of sMICA and NKG2D are abnormal and negatively correlated with one another in pancreatic carcinoma tissues; they may be considered as valuable biomarkers for the prognosis of pancreatic carcinoma. © 2016 Chen et al.


Sun Q.-K.,Anhui Medical University | Zhu J.-Y.,Anhui Medical University | Wang W.,Anhui Medical University | Lv Y.,Anhui Medical University | And 8 more authors.
Medical Oncology | Year: 2014

Peroxiredoxin 1 (Prdx1) is a member of the peroxiredoxin family of antioxidant enzymes and implicated in cell differentiation, proliferation, and apoptosis. The aim of the present study was to determine the expression and diagnostic and prognostic significance of Prdx1 in human hepatocellular carcinoma (HCC). Prdx1 expression was examined in 76 HCC patients and 20 healthy volunteers. The relationships between Prdx1 expression and clinicopathological features were analyzed. Receiver operating characteristics analysis was used to calculate the diagnostic accuracy of serum Prdx1, serum alpha-fetoprotein (AFP), and their combination. The prognostic impact of Prdx1 on overall survival (OS) and disease-free survival (DFS) of HCC patients was investigated. Prdx1-positive rate was significantly (p < 0.05) higher in HCC (77.1 %) than in adjacent non-tumorous liver tissues (18.4 %). Prdx1 immunoreactivity was positively correlated with tumor vascular endothelial growth factor expression and microvessel density. Prdx1 expression was significantly associated with tumor size, microvascular invasion, Edmondson grade, tumor capsula status, serum AFP, and tumor-node-metastasis stage. The combination of serum Prdx1 and AFP had a markedly higher area under the curve than serum Prdx1 alone. Positive Prdx1 expression was associated with unfavorable OS (p = 0.004) and DFS (p = 0.001). Multivariate analysis revealed intra-tumoral Prdx1 staining as an independent poor prognostic marker for OS (p = 0.006) and DFS (p = 0.002). Taken together, our data suggest that increased Prdx1 expression is associated with tumor angiogenesis and progression in HCC and serves as a promising biomarker for detection and prognosis of this malignancy. © 2013 Springer Science+Business Media New York.


Ma J.,Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery | Ma J.,Anhui Medical University | Sheng Z.,Anhui University of Science and Technology | Lv Y.,Anhui Medical University | And 9 more authors.
OncoTargets and Therapy | Year: 2016

Objective: Nectin-4 is a member of the Nectin family of four Ca+-independent immunoglobulin-like cell adhesion molecules and implicated in cell adhesion, movement, proliferation, differentiation, polarization, and survival. The aberrant expression of Nectin-4 has been found in a variety of tumors; however, its expression in hepatocellular carcinoma (HCC) is still poorly understood. This study was to investigate the expression of Nectin-4 and its clinical significance in the patients with HCC. Methods: The expression of Nectin-4 was assessed at mRNA and protein levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting assays in 20 HCC specimens and adjacent non-tumor live tissues. Furthermore, the clinical significance of Nectin-4 in 87 cases of HCC was confirmed by immunohistochemistry. Results: The mRNA and protein levels of Nectin-4 were higher in HCC tumor tissues than in the matched non-tumor tissues. Nectin-4 was located in the cytoplasm of tumor cells and over-expressed in 67.82% (59/87) HCC tissues by immunohistochemical staining. Positive Nectin-4 expression was significantly correlated with tumor size (P=0.029), status of metastasis (P=0.023), vascular invasion (P=0.018) and tumor-node-metastasis stage (P=0.003). In addition, Kaplan-Meier survival analysis indicated that positive Nectin-4 expression was associated with worse recurrence-free survival (RFS) and overall survival (OS) (P=0.006 and P=0.005, respectively). In multivariate analysis, Nectin-4 was an independent prognostic factor for RFS and OS in the patients with HCC. Conclusion: Nectin-4 is upregulated in HCC and may be a novel prognostic biomarker for the patients after surgical resection. © 2016 Ma et al.


Zhai L.-L.,Anhui Medical University | Zhai L.-L.,Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery | Wu Y.,Anhui Medical University | Wu Y.,Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery | And 4 more authors.
OncoTargets and Therapy | Year: 2015

Background: Dysregulated expression of matrix metalloproteinase (MMP)-2 and tissue factor pathway inhibitor (TFPI)-2 is closely associated with tumorigenesis and tumor progression. The aim of this work was to determine the predictive values of MMP-2 and TFPI-2 in identifying lymph node metastasis (LNM) and perineural invasion (PNI) in pancreatic carcinoma. Methods: Formalin-fixed and paraffin-embedded tissue samples containing pancreatic carcinoma tissues and their corresponding para-carcinoma tissues were obtained from 122 patients with pancreatic carcinoma. The expression levels of MMP-2 and TFPI-2 were evaluated by immunohistochemistry. The roles of MMP-2 and TFPI-2 in predicting LNM and PNI in pancreatic carcinoma were analyzed. Results: The level of MMP-2 expression was markedly increased in pancreatic carcinoma tissues (76.9%) compared with para-carcinoma tissues (29.2%; P<0.05). In contrast, there was obviously decreased TFPI-2 expression level in pancreatic carcinoma tissues (29.2%) compared with para-carcinoma tissues (77.7%; P<0.001). Additionally, MMP-2 expression was significantly positively correlated with LNM (r=0.468, P<0.01) and PNI (r=0.637, P<0.01). In contrast, TFPI-2 expression was strongly negatively correlated with LNM (r=-0.396, P<0.001) and PNI (r=-0.460, P<0.001). Logistic regression analysis showed that high MMP-2 expression and low TFPI-2 expression acted as independent predictors for LNM and PNI in pancreatic carcinoma. Conclusion: Taken together, our findings suggest that upregulated MMP-2 and downregulated TFPI-2 serve as useful predictors for a high risk of LNM and PNI. Obtaining information on the expression of MMP-2 and TFPI-2 before surgery may predict the occurrence of LNM and PNI, thereby permitting reasonable and effective surgical treatment for patients with pancreatic carcinoma. © 2015 Zhai et al.

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