scholarly journals High JAK2 Protein Expression Predicts a Poor Prognosis in Patients with Resectable Pancreatic Ductal Adenocarcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yang Song ◽  
Mei-Yue Tang ◽  
Wei Chen ◽  
Zhe Wang ◽  
Si-Liang Wang

Background. Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies worldwide. The JAK/STAT signaling pathway is involved in pancreatic cancer tumorigenesis. However, the prognostic value of JAK2 expression in resectable PDAC is unclear. Method. In this study, we performed a clinicopathological analysis of 62 resectable PDAC cases with a primary focus on survival. JAK2 expression was examined by immunohistochemistry. The relationship between JAK2 expression and clinicopathological features and prognosis was analyzed. Results. Survival curve analyses revealed that high levels of JAK2 expression predict a poor prognosis in resectable PDAC patients. Multivariate analysis confirmed that JAK2 expression can predict the prognosis of PDAC. Conclusions. Assessment of JAK2 protein expression may be a promising method to predict prognosis in patients with resectable PDAC.

2021 ◽  
Author(s):  
Hao Yu ◽  
Xiaoping Mei ◽  
Xueming Zhang ◽  
Neng Qian ◽  
Qingjiang Yu ◽  
...  

Abstract Objective: Pancreatic ductal adenocarcinoma (PDAC) serves as a prevailing tumor type with high mortality and poor prognosis. The study aims to explore the mechanism of gemcitabine resistance in PDAC patients. Methods: Immunohistochemistry(IHC)was used to analyze the expression of SLC39A1 in PDAC samples. PDAC cells were culture and transfected with siSLC39A1 and siNC, respectively. Cell proliferation analysis was performed using CCK-8 assay. And qPCR and Western blotting was used to analysis the expression level of SLC39A1 and related signal molecular in cells. Results: IHC results demonstrated that the SLC39A1 expression was significantly up-regulated in the gemcitabine-resistant PDAC samples compared with gemcitabine-sensitive PDAC samples. The treatment of gemcitabine dose-dependently inhibited the viability of the PDAC cells. Meanwhile, the mRNA and protein expression of SLC39A1 were elevated in the gemcitabine-resistant PDAC. The treatment of gemcitabine remarkably decreased viability of PDACs, in which SLC39A1 depletion could reverse this effect. SLC39A1 knockdown could reverse the gemcitabine-induced phosphorylation of AMPK enhanced and gemcitabine-inhibited S6K expression. Conclusion: SLC39A1 contributed to gemcitabine resistance of PDAC by activating AMPK signaling.


2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Hong Luan ◽  
Chuang Zhang ◽  
Tuo Zhang ◽  
Ye He ◽  
Yanna Su ◽  
...  

Pancreatic ductal adenocarcinoma (PDAC) is an extremely malignant tumor. The immune profile of PDAC and the immunologic milieu of its tumor microenvironment (TME) are unique; however, the mechanism of how the TME engineers the carcinogenesis of PDAC is not fully understood. This study is aimed at better understanding the relationship between the immune infiltration of the TME and gene expression and identifying potential prognostic and immunotherapeutic biomarkers for PDAC. Analysis of data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases identified differentially expressed genes (DEGs), including 159 upregulated and 53 downregulated genes. Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment were performed and showed that the DEGs were mainly enriched for the PI3K-Akt signaling pathway and extracellular matrix organization. We used the cytoHubba plugin of Cytoscape to screen out the most significant ten hub genes by four different models (Degree, MCC, DMNC, and MNC). The expression and clinical relevance of these ten hub genes were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the Human Protein Atlas, respectively. High expression of nine of the hub genes was positively correlated with poor prognosis. Finally, the relationship between these hub genes and tumor immunity was analyzed using the Tumor Immune Estimation Resource. We found that the expression of SPARC, COL6A3, and FBN1 correlated positively with infiltration levels of six immune cells in the tumors. In addition, these three genes had a strong coexpression relationship with the immune checkpoints. In conclusion, our results suggest that nine upregulated biomarkers are related to poor prognosis in PDAC and may serve as potential prognostic biomarkers for PDAC therapy. Furthermore, SPARC, COL6A3, and FBN1 play an important role in tumor-related immune infiltration and may be ideal targets for immune therapy against PDAC.


Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769912 ◽  
Author(s):  
Xin Luo ◽  
Zhulin Yang ◽  
Xiao Liu ◽  
Ziru Liu ◽  
Xiongying Miao ◽  
...  

Pancreatic ductal adenocarcinoma is a highly malignant tumor with poor prognosis, and the biomarkers for the early diagnosis, targeting therapy, and prognosis are still not clinically available. This study investigated the expression of forkhead box P1 and forkhead box O3a proteins in human pancreatic ductal adenocarcinoma tumor tissues and pancreatic tissues with and without benign lesions using immunohistochemical staining. Results showed that the positive rates of forkhead box P1 and forkhead box O3a protein expression were significantly lower in pancreatic ductal adenocarcinoma tumors compared to peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (p < 0.01). Pancreatic tissues with negative forkhead box P1 and forkhead box O3a protein expression exhibited dysplasia or intraepithelial neoplasia. The positive rates of forkhead box P1 and forkhead box O3a expression were significantly lower in cases with tumor mass >5 cm, lymph node metastasis, invasion to surrounding tissues and organs, and tumor–node–metastasis III + IV stage disease compared to cases with tumor mass ⩽5 cm (p < 0.05), no lymph node metastasis (p < 0.001 and p = 0.001, respectively), no invasion (p = 0.003 and p = 0.004, respectively), and tumor–node–metastasis I or II stage disease (p < 0.05). Kaplan–Meier survival analysis showed that pancreatic ductal adenocarcinoma patients with negative forkhead box P1 and forkhead box O3a expression survived significantly shorter than patients with positive forkhead box P1 and forkhead box O3a expression (p = 0.000). Cox multivariate analysis revealed that negative forkhead box P1 and forkhead box O3a expression was an independent poor prognosis factor in pancreatic ductal adenocarcinoma patients. The area under the curve of a receiver operating characteristic curve was 0.642 for forkhead box P1 (95% confidence interval: 0.553–0.730) and 0.655 for forkhead box O3a (95% confidence interval: 0.6568–0.742). Loss of forkhead box P1 and forkhead box O3a protein expression is associated with carcinogenesis, progression, and poor prognosis in patients with pancreatic ductal adenocarcinomas.


2017 ◽  
Vol 99 (2) ◽  
pp. 101-106 ◽  
Author(s):  
M Elshaer ◽  
G Gravante ◽  
M Kosmin ◽  
A Riaz ◽  
A Al-Bahrani

BACKGROUND Pancreatic ductal adenocarcinoma is the most common pancreatic cancer. Five-year overall survival is currently 3.3–6.0%. The aim of this review was to evaluate the prognostic value of lymph node ratio, number of positive nodes and total nodes examined on overall survival rate following pancreatic resection. MATERIALS AND METHODS A literature search was conducted of MEDLINE, EMBASE, the Cochrane Library and Central Register of Controlled Trials and the Cochrane Database of Systematic Review databases, from January 1996 to January 2016. RESULTS Overall, 19 studies including 4,883 patients examined the relationship between lymph node ratio and overall survival. A high lymph node ratio was associated with decreased overall survival in 17 studies. A total of 12 studies examined the relationship between the number of positive nodes and overall survival, and 11 studies revealed that an increase in the number of positive nodes was associated with decreased overall survival. In 15 studies examining the relationship between the total nodes examined and overall survival, there was no association with overall survival in 12 studies. CONCLUSIONS Lymph node ratio and number of positive nodes are factors associated with overall survival in pancreatic ductal adenocarcinoma, but not total nodes examined.


Cancer ◽  
2006 ◽  
Vol 107 (2) ◽  
pp. 251-257 ◽  
Author(s):  
Norihiro Sato ◽  
Noriyoshi Fukushima ◽  
Hiroyuki Matsubayashi ◽  
Christine A. Iacobuzio-Donahue ◽  
Charles J. Yeo ◽  
...  

Tumor Biology ◽  
2015 ◽  
Vol 36 (12) ◽  
pp. 9189-9199 ◽  
Author(s):  
Chen Gong ◽  
Yixin Zhang ◽  
Yinji Chen ◽  
Haifeng Zhang ◽  
Xiaorong Liu ◽  
...  

2020 ◽  
Author(s):  
xuyang ma ◽  
Ying Ding ◽  
Li Zeng

Abstract Background: The potential correlation between H2AFY (also known as MacroH2A1) and the clinical characteristics of hepatocellular carcinoma (HCC) patients was analysed through gene expression profiles and clinical data in The Cancer Genome Atlas (TCGA) database, and the diagnostic and prognostic value of H2AFY in HCC was discussed. Methods: The gene expression data of HCC and the corresponding clinical characteristics of HCC patients were downloaded from the TCGA database. The differences in H2AFY in normal liver tissues and HCC were analysed. The relationship between H2AFY and clinical characteristics was analysed by Wilcoxon signed-rank test, logistic regression and Kruskal-Wallis test. The Kaplan-Meier method and the Cox regression method were used to analyse the relationship between overall survival and clinical characteristics of the patients. An ROC curve was used to predict the diagnostic value of H2AFY in HCC. Gene set enrichment analysis (GSEA) was used to analyse the pathway enrichment of H2AFY. Result: Compared with normal liver tissues, H2AFY was significantly highly expressed in HCC. H2AFY was positively correlated with the age, clinical stage, G stage (grade) and T stage (tumor stage) of liver cancer patients. Higher H2AFY expression predicted a poor prognosis in HCC patients. Cox regression analysis suggested that H2AFY was an independent risk factor for the prognosis of HCC patients. The ROC curve suggested that H2AFY had certain diagnostic value in HCC. GSEA suggested that H2AFY was correlated with lipid metabolism and a variety of tumour pathways. Conclusion: Our study showed that H2AFY was significantly overexpressed in HCC. H2AFY may be a potential diagnostic and prognostic marker for HCC, and high expression of H2AFY predicts a poor prognosis in patients with HCC.


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