scholarly journals DAPK1 as an independent prognostic marker in liver cancer

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3568 ◽  
Author(s):  
Ling Li ◽  
Libin Guo ◽  
Qingshui Wang ◽  
Xiaolong Liu ◽  
Yongyi Zeng ◽  
...  

The death-associated protein kinase 1 (DAPK1) can act as an oncogene or a tumor suppressor gene depending on the cellular context as well as external stimuli. Our study aims to investigate the prognostic significance of DAPK1 in liver cancer in both mRNA and protein levels. The mRNA expression of DAPK1 was extracted from the Gene Expression Omnibus database in three independent liver cancer datasets while protein expression of DAPK1 was detected by immunohistochemistry in our Chinese liver cancer patient cohort. The associations between DAPK1 expression and clinical characteristics were tested. DAPK1 mRNA expression was down-regulated in liver cancer. Low levels of DAPK1 mRNA were associated with shorter survival in a liver cancer patient cohort (n = 115; p = 0.041), while negative staining of DAPK1 protein was significantly correlated with shorter time to progression (p = 0.002) and overall survival (p = 0.02). DAPK1 was an independent prognostic marker for both time to progression and overall survival by multivariate analysis. Liver cancer with the b-catenin mutation has a lower DAPK1 expression, suggesting that DAPK1 may be regulated under the b-catenin pathway. In addition, we also identified genes that are co-regulated with DAPK1. DAPK1 expression was positively correlated with IRF2, IL7R, PCOLCE and ZBTB16, and negatively correlated with SLC16A3 in both liver cancer datasets. Among these genes, PCOLCE and ZBTB16 were significantly down-regulated, while SLC16A3 was significantly upregulated in liver cancer. By using connectivity mapping of these co-regulated genes, we have identified amcinonide and sulpiride as potential small molecules that could potentially reverse DAPK1/PCOLCE/ZBTB16/SLC16A3 expression. Our study demonstrated for the first time that both DAPK1 mRNA and protein expression levels are important prognostic markers in liver cancer, and have identified genes that may contribute to DAPK1-mediated liver carcinogenesis.

2020 ◽  
Vol 21 (12) ◽  
pp. 4418
Author(s):  
Alaleh Zati Zehni ◽  
Udo Jeschke ◽  
Anna Hester ◽  
Thomas Kolben ◽  
Nina Ditsch ◽  
...  

The aim of this study was to evaluate the prognostic impact of prostaglandin E2 receptor 3 (EP3) receptor expression might have on the two different breast cancer entities: multifocal/multicentric versus unifocal. As the prognosis determining aspects, we investigated the overall- and disease-free survival by uni-and multivariate analysis. To underline the study’s conclusion, we additionally considered the histopathological grading and the tumor node metastasis (TNM) staging system. A retrospective statistical analysis was performed on survival related events in a series of 289 sporadic breast cancer (BC) patients treated at the Department of Obstetrics and Gynecology at the Ludwig–Maximillian’s University in Munich between 2000 and 2002. The EP3 receptor expression was analyzed by immunohistochemistry and showed to have a significantly positive association with breast cancer prognosis for both entities, although with major differences. Patients with unifocal BC with EP3 receptor expression showed a significant improved overall survival, in contrast to the patient cohort with multifocal/multicentric BC. In this group, EP3 expression revealed its positive impact merely five years after initial diagnosis. Underlining the positive influence of EP3 as a positive prognosticator notably for unifocal breast cancer, only this patient cohort showed favorable outcomes in staging and grading. Especially EP3 expression in unifocal breast cancer was identified as an independent prognostic marker for the overall survival, when adjusted for age, grading, and staging. Altogether, our results strengthen the need to further investigate the behavior of EP3 in breast cancer and understand why markers linked to inflammation show different effects on prognosis and clinicopathological parameters on each focality type.


2013 ◽  
Vol 108 (2) ◽  
pp. 278-284 ◽  
Author(s):  
R Bertorelle ◽  
M Briarava ◽  
E Rampazzo ◽  
L Biasini ◽  
M Agostini ◽  
...  

2014 ◽  
Vol 50 ◽  
pp. 25
Author(s):  
M. Fabre ◽  
D. Nicolle ◽  
A. Gorse ◽  
O. Déas ◽  
C. Mussini ◽  
...  

2020 ◽  
Author(s):  
Xiao-Han Cui ◽  
Bei Zhu ◽  
Li Fu ◽  
Yuan-Xiang Lao ◽  
Chun-Fu Zhu ◽  
...  

Abstract Cancer is the leading cause of death worldwide, despite advances in the treatment of cancer, mortality of liver cancer remains high. The Microliposome maintenance (MCM) family has been reported to be involved in a variety of diseases. However, little is known about its expression and prognostic value in liver cancer. In this study, we analyzed the expression of the MCM family in liver cancer tissues and normal liver tissues. Oncomine and GEPIA were used to analyze the mRNA expression level of MCM family in liver cancer and other cancers. We observed that the mRNA expression levels of MCM1-8 and MCM10 are higher than normal tissues in most cancers. In addition, the expression levels of MCM1-10 were highly expressed in liver cancer cell lines, analyzed by Cancer Cell Line Encyclopedia (CCLE) and European Bioinformatics Institute (EMBL-EBI) databases. Furthermore, LinkedOmics and GEPIA databases were used to evaluate correlation between MCM1-10 and overall survival of patients. In the LinkedOmics-based survival analysis, high expressions of MCM2-8 and MCM10 were associated with worse patient prognosis (OS). The results showed that there was no correlation between the expression levels of MCM1 and MCM9 and prognosis of patients’ prognosis. The GEPIA dataset was also used for overall survival analysis, and the results also support the results of LinkedOmics.In conclusion, the MCM family has the potential to become a biomarker, especially MCM2-8 and MCM10 are probably the most promising biomarkers for liver cancer prognosis.


2021 ◽  
Author(s):  
Meihua Jin ◽  
Woo Kyung Lee ◽  
Mi-Hyeon You ◽  
Ahreum Jang ◽  
Sheue-yann Cheng ◽  
...  

Background: Catabolism of serine via serine hydroxymethyltransferase2 (SHMT2) through the mitochondrial one-carbon unit pathway is important in tumorigenesis. Therefore, SHMT2 may play a role in thyroid cancer. Methods: Thyroid tissue samples and The Cancer Genome Atlas (TCGA) database were used to evaluate SHMT2 expression in thyroid tissues and the association with clinical outcomes. Results: SHMT2 protein expression was evaluated in thyroid tissues consisting of 52 benign nodules, 129 papillary thyroid carcinomas (PTC) and matched normal samples, and 20 anaplastic thyroid carcinomas (ATC). ATCs presented the highest (95.0%) positivity of SMHT2 protein expression. PTCs showed the second highest (73.6%) positivity of SHMT2 expression, which was significantly higher than that of benign nodules (19.2%, P =0.016) and normal thyroid tissues (0%, P<0.001). Analysis of TCGA data showed that SHMT2 messenger ribonucleic acid (mRNA) expression was significantly higher in tumors than normal tissues (P<0.001). When we classified thyroid cancer into high and low groups according to SHMT2 mRNA expression levels, the thyroid differentiation score for the high SHMT2 group was significantly lower than that of the low SHMT2 group (P<0.001). There was also a significant correlation between SHMT2 mRNA expression and the stemness index (r=0.41, P<0.001). High SHMT2 group had more advanced TNM stages and shorter progression-free survival rates than low SHMT2 group (P<0.01 and P =0.007, respectively). Conclusion: SHMT2 expression is higher in thyroid cancers than normal or benign tissues and is associated with dedifferentiation and poor clinical outcomes. Thus, SHMT2 might be useful as a diagnostic and prognostic marker for thyroid cancer.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15568-e15568
Author(s):  
Guoqin Zheng ◽  
Yan Han ◽  
Jian Zhang ◽  
Bian Li ◽  
Dong Chen ◽  
...  

e15568 Background: To investigate the sustaining time of 99mTc labeled cytarabine in the tumor of liver cancer patients by ROS under ECT imaging instrument. Methods: A liver cancer patient with 2 lesions in the liver was enrolled in this study. After obtaining informed consent and excluding relevant contraindications, two tumors in the liver of the patient were guided by single photon emission computed tomography (ECT). Injecting the drug, the tumor was injected with 99m TC-labeled cytarabine solution as control, the tumor was injected with 99m TC-labeled cytarabine + hydrogen peroxide solution (ROS) as experimental, and the two tumor masses were detected by ECT imaging, with an intensity of 1h as background. The drug retention rate was calculated by caculated of deduction of the baseline (minus background) at 1h, 3h, and 23h. Results: The patient was detected by ECT on the right laid down position. The area of the region of interest was 679 account by Gama detector, and the background level of the liver was 494 account. The acquisition time was about 400 seconds as a standard acquisition. The ECT imaging showed that the labeling rate of 99mTC-labeled cytarabine was about 100%. The drug of 99mTC-labeled cytarabineretentionrates in tumor lesions with ROS at 1 hours, 3 hours, and 23 hours were 97.83%, 81.63%, and 60.72%, respectively; the drug retention rates in tumor lesions without ROS at 1 hours, 3 hours, and 23 hours were 44.74%, 15.87%, and 0, respectively. Conclusions: The ROS can hold drug in the tumor long time after the intratumoral injection of drugs with ROS whichoxidant with the extracellular matrix and interstitial of the tumor to cause degeneration and deformation so that drug of Ara-C sustaining in tumor for a long time, and the tumor cells are also degenerated and necrotic and died, so that high concentrations of cytarabine are embedded between the denatured tumor tissues and cells. The drug slowly released from the inside to the outside to kill tumor cells. IT is further confirmed that the ROS is a sustained release agent intratumorally injection and it can significantly increase the residence time of 99mTc-labeled cytarabine in the tumor, prolong the drug action time of cytarabine, and improve the effect of killing tumor cells.


2018 ◽  
Vol 96 (12) ◽  
pp. 1246-1254 ◽  
Author(s):  
Kaikun Liu ◽  
Yumin Li ◽  
Bo Yu ◽  
Furong Wang ◽  
Taiyu Mi ◽  
...  

The present study was designed to investigate the significance of non–structural maintenance of chromosomes (non-SMC) chromosome-associated polypeptide G (NCAPG), a subunit of condensin complex I, in the development of hepatocellular carcinoma (HCC). NCAPG protein expression in human HCC and paracancerous hepatic tissues were examined using immunohistochemistry, and NCAPG mRNA expression in HCC cell lines were quantified using quantitative RT–PCR. Lentivirus-mediated RNA interference was used to silence NCAPG in HCC cells. Cell proliferation was monitored by MTT assay. Cell colony-forming capacity was measured by colony formation assay. Apoptosis was determined by flow cytometry. The results showed that increased protein expression of NCAPG was found in HCC tissues compared with the matched paracancerous hepatic tissues. At the mRNA level, increased expression of NCAPG was found in HCC cells as opposed to the normal hepatocytes. Silencing of NCAPG in BEL-7404 and SMMC-7721 cells led to decreased cell proliferation and increased apoptosis. These changes were associated with increased mRNA expressions of P53, P27, and Bad, but decreased mRNA expression of EGFR, Akt, survivin, and JNK. NCAPG might play an oncogenic role in the development of liver cancer. Further studies to clarify its role and underlying mechanisms in the development of liver cancer are warranted.


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