Phosphomannose Isomerase High Expression Associated with Better Prognosis in Pancreatic Ductal Adenocarcinoma

Background. Pancreatic cancer is a malignant tumor of the digestive tract, which is difficult to diagnose and treat due to bad early diagnosis. We aimed to explore the role of kinesin superfamily 4A (KIF4A) in pancreatic ductal adenocarcinoma (PDAC). Methods. We first used the bioinformatic website to screen the data of pancreatic cancer in TCGA, and KIF4A protein was detected among the 86 specimens of patients in our hospital combined with clinic-pathological characteristics and survival analysis. KIF4A loss-expression cell lines were established by RNA interference (RNAi). In addition, we performed in vitro cell assays to detect the changes in cell proliferation, migration, and invasion. The proteins involved in the proliferation and metastasis of cancer cells were also detected by western blot. The above results could be proved in vivo. Further, the correlation between KIF4A and CDC5L was analyzed by TCGA and IHC data. Results. We first found a high expression of KIF4A in pancreatic cancer, suggesting a role of KIF4A in the development of pancreatic cancer. KIF4A was found to be differentially expressed ( P < 0.05 ) among the 86 specimens of patients in our hospital and was significantly associated with PDAC TNM stages and tumor size. High KIF4A expression also significantly worsened overall survival (OS) and disease-free survival rate (DFS) ( P < 0.05 , respectively). In addition, cell proliferation, migration, and invasion were inhibited by the KIF4A-shRNA group compared with the control ( P < 0.05 , respectively). In the end, knockdown of KIF4A could inhibit tumor development and metastasis in vivo. Further, the positive correlation between KIF4A and CDC5L existed, and KIF4A might promote pancreatic cancer proliferation by affecting CDC5L expression. Conclusion. In conclusion, the high expression level of KIF4A in PDAC was closely related to poor clinical and pathological status, lymphatic metastasis, and vascular invasion. KIF4A might be involved in promoting the development of PDAC in vitro and in vivo, which might be a new therapeutic target of PDAC.

Download Full-text

High Expression of Cancer-Derived Glycosylated Immunoglobulin G Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma

Journal of Cancer ◽

10.7150/jca.39800 ◽

2020 ◽

Vol 11 (8) ◽

pp. 2213-2221

Author(s):

Ming Cui ◽

Lei You ◽

Bang Zheng ◽

Xinmei Huang ◽

Qiaofei Liu ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Immunoglobulin G ◽

Poor Prognosis ◽

High Expression ◽

Ductal Adenocarcinoma

Download Full-text

High expression of CDK1 and BUB1 predicts poor prognosis of pancreatic ductal adenocarcinoma

Gene ◽

10.1016/j.gene.2019.02.081 ◽

2019 ◽

Vol 701 ◽

pp. 15-22 ◽

Cited By ~ 17

Author(s):

Junjie Piao ◽

Lianhua Zhu ◽

Jie Sun ◽

Nan Li ◽

Bing Dong ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Poor Prognosis ◽

High Expression ◽

Ductal Adenocarcinoma

Download Full-text

Analysis of associations of CXCR3 ligands with immune microenvironment and aggressiveness in murine and human pancreatic ductal adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.762 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 762-762

Author(s):

Andrew Cannon ◽

Christopher M Thompson ◽

Pranita Atri ◽

Rakesh Bhatia ◽

Sushil Kumar ◽

...

Keyword(s):

Overall Survival ◽

T Cell ◽

Pancreatic Ductal Adenocarcinoma ◽

Nk Cell ◽

Cd8 T Cell ◽

High Expression ◽

Ductal Adenocarcinoma ◽

Bioinformatics Analyses ◽

Dismal Prognosis ◽

M1 Macrophage

762 Background: The complex milieu of cytokines within pancreatic ductal adenocarcinoma (PDAC) promotes tumor progression and immune suppression thereby contributing to the dismal prognosis of patients with PDAC. However, the roles of many cytokines, including CXCR3 ligands, in PDAC have not been thoroughly investigated. Methods: Bioinformatics analyses of PDAC microarray and TCGA datasets were used to identify cytokines overexpressed in PDAC, their association with patient survival as well as the expression of cognate cytokine receptors. Comparative analysis of cytokine expression in KrasLSL-G12D-P53LSL-R172H-Pdx1-Cre (KPC) and KrasLSL-G12D-Pdx1-Cre (KC) murine PDAC models were used to validate these findings. Pathway and CIBERSORT analyses were employed to determine mechanistic basis of altered survival associated with cytokines of interest. Results: Of the 149 cytokines analyzed, CXCR3 ligands CXCL9 and CXCL10 were highly and consistently overexpressed in PDAC datasets. Concurrently, CXCL9, CXCL10 and PF4 were overexpressed in the aggressive KPC murine model compared to the indolent KC model. CXCR3 showed robust expression in PDAC in microarray, TCGA and IHC analyses. Interestingly, high expression of CXCR3 ligands was associated with shorter overall survival (p = 0.04 for CXCL9, 10 and 11 and p = 0.02 for PF4) while high expression of CXCR3 was associated with increased overall survival (p = 0.03). Pathway analysis of genes correlated with CXCR3 and/or its ligands showed that CXCR3 ligands may promote T-cell exhaustion (p < 0.001). Finally, CIBERSORT analysis of TCGA data demonstrated that high CXCR3 expression was associated with increased CD8 T-cell and naïve B-cell signatures and loss of plasma cells signatures. High CXCR3 ligand expression was associated with increased CD8 T-cell, and M1 macrophage, and loss of NK-cell signatures(p < 0.05). Conclusions: CXCR3 ligands are overexpressed in PDAC and are associated with poor survival, likely related to alterations in tumor immune infiltrate/activity and may represent targets to augment anti-tumor immunity.

Download Full-text

High Expression of FAM83B Predicts Poor Prognosis in Patients with Pancreatic Ductal Adenocarcinoma and Correlates with Cell Cycle and Cell Proliferation

Journal of Cancer ◽

10.7150/jca.20086 ◽

2017 ◽

Vol 8 (16) ◽

pp. 3154-3165 ◽

Cited By ~ 11

Author(s):

Chao-qin Shen ◽

Ting-Ting Yan ◽

Wei Liu ◽

Xiao-qiang Zhu ◽

Xiang-long Tian ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Pancreatic Ductal Adenocarcinoma ◽

Poor Prognosis ◽

High Expression ◽

Ductal Adenocarcinoma

Download Full-text

High expression of Annexin A2 is associated with DNA repair, metabolic alteration, and worse survival in pancreatic ductal adenocarcinoma

Surgery ◽

10.1016/j.surg.2019.04.011 ◽

2019 ◽

Vol 166 (2) ◽

pp. 150-156 ◽

Cited By ~ 13

Author(s):

Hideo Takahashi ◽

Eriko Katsuta ◽

Li Yan ◽

Subhamoy Dasgupta ◽

Kazuaki Takabe

Keyword(s):

Dna Repair ◽

Pancreatic Ductal Adenocarcinoma ◽

Annexin A2 ◽

High Expression ◽

Ductal Adenocarcinoma ◽

Metabolic Alteration

Download Full-text

DNA-Methylation-Caused Downregulation of miR-30 Contributes to the High Expression of XPO1 and the Aggressive Growth of Tumors in Pancreatic Ductal Adenocarcinoma

Cancers ◽

10.3390/cancers11081101 ◽

2019 ◽

Vol 11 (8) ◽

pp. 1101 ◽

Cited By ~ 1

Author(s):

Asfar S. Azmi ◽

Yiwei Li ◽

Amro Aboukameel ◽

Irfana Muqbil ◽

Philip A. Philip ◽

...

Keyword(s):

Pancreatic Cancer ◽

Pancreatic Ductal Adenocarcinoma ◽

Cancer Cells ◽

Nuclear Export ◽

The United States ◽

High Expression ◽

Ductal Adenocarcinoma ◽

Multiple Tumor ◽

Pancreatic Cancer Cells

Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, with high mortality in the United States. One of the important signal transduction proteins involved in the regulation of pancreatic cancer’s aggressive progression is the nuclear export protein (XPO1). High expression of XPO1 has been found in pancreatic, lung, breast and other cancers and lymphomas with a poor prognosis of patients with tumors and high proliferative activity of cancer cells. Because XPO1 exports multiple tumor suppressor proteins simultaneously from the nucleus, the inhibition of XPO1 may retain multiple tumor suppressors in the nucleus, resulting in the suppression of cell proliferation and the induction of apoptosis in tumors. In this study, we found that the high expression of XPO1 in pancreatic cancer cells could be, in part, due to the methylation of the miR-30 gene, leading to the low expression level of the miR-30 family. By co-transfection of the XPO1 3′-UTR-Luc target vector with miR-30 mimic, we found that XPO1 is a direct target of the miR-30 family. We also observed that the enforced expression of the miR-30 family inhibited the expression of XPO1, resulting in the suppression of pancreatic cancer growth both in vitro and in vivo. These findings could help to design a novel therapeutic strategy for the treatment of pancreatic cancer by introducing miR-30 into cancer cells.

Download Full-text