scholarly journals High Trophinin‑Associated Protein Expression and Its Role in Prognosis of Pancreatic Cancer

2020 ◽  
Author(s):  
Ruobing Wang ◽  
Yan Jiao ◽  
Yanqing Li ◽  
Yueyuan Wang ◽  
Yang Li ◽  
...  

Abstract Background: Trophinin‑associated protein (TROAP) was known as the tastin, which originally recognized as a cytosolic protein involved in embryo implantation. Increasing studies have revealed that high expression of TROAP is related with poor outcomes in cancers. However, there have been few studies on the correlation of TROAP and pancreatic cancer. This study aimed to explore the prognostic significance of TROAP in pancreatic cancer by mining the data collected from The Cancer Genome Atlas (TCGA) dataset. Methods: Clinical information and the RNA expression data were obtained from the TCGA dataset. The correlations between clinical information and TROAP mRNA expression were performed by chi-square and Fisher exact tests. Univariate Cox analyses were used to filter the potential prognostic factors. The correlations between TROAP expression and clinical characteristics of patients with pancreatic cancer were confirmed by multivariate Cox analyses.Results: Analysis of tumor data showed that high expression of TROAP was correlated with poor outcomes in pancreatic cancer patients. Univariate and multivariate Cox analyses demonstrated that TROAP mRNA expression played an important role in shorting overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for pancreatic cancer. Conclusions: TROAP was an independent risk factor for pancreatic cancer. TROAP has the potential to be a biomarker, especially in predicting prognosis.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ruobing Wang ◽  
Yan Jiao ◽  
Yanqing Li ◽  
Siyang Ye ◽  
Guoqiang Pan ◽  
...  

Liver cancer is a devastating disease for humans with poor prognosis. Although the survival rate of patients with liver cancer has improved in the past decades, the recurrence and metastasis of liver cancer are still obstacles for us. Inositol polyphosphate-5-phosphatase K (INPP5K) belongs to the family of phosphoinositide 5-phosphatases (PI 5-phosphatases), which have been reported to be associated with cell migration, polarity, adhesion, and cell invasion, especially in cancers. However, there have been few studies on the correlation of INPP5K and liver cancer. In this study, we explored the prognostic significance of INPP5K in liver cancer through bioinformatics analysis of data collected from The Cancer Genome Atlas (TCGA) database. Chi-square and Fisher exact tests were used to evaluate the relationship between INPP5K expression and clinical characteristics. Our results showed that low INPP5K expression was correlated with poor outcomes in liver cancer patients. Univariate and multivariate Cox analyses demonstrated that low INPP5K mRNA expression played a significant role in shortening overall survival (OS) and relapse-free survival (RFS), which might serve as the useful biomarker and prognostic factor for liver cancer. In conclusion, low INPP5K mRNA expression is an independent risk factor for poor prognosis in liver cancer.


Cancers ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 126 ◽  
Author(s):  
Remy Nicolle ◽  
Jerome Raffenne ◽  
Valerie Paradis ◽  
Anne Couvelard ◽  
Aurelien de Reynies ◽  
...  

Data from the Cancer Genome Atlas (TCGA) are now easily accessible through web-based platforms with tools to assess the prognostic value of molecular alterations. Pancreatic tumors have heterogeneous biology and aggressiveness ranging from the deadly adenocarcinoma (PDAC) to the better prognosis, neuroendocrine tumors. We assessed the availability of the pancreatic cancer TCGA data (TCGA_PAAD) from several repositories and investigated the nature of each sample and how non-PDAC samples impact prognostic biomarker studies. While the clinical and genomic data (n = 185) were fairly consistent across all repositories, RNAseq profiles varied from 176 to 185. As a result, 35 RNAseq profiles (18.9%) corresponded to a normal, inflamed pancreas or non-PDAC neoplasms. This information was difficult to obtain. By considering gene expression data as continuous values, the expression of the 5312 and 4221 genes were significantly associated with the progression-free and overall survival respectively. Considering the cohort was not curated, only 4 and 14, respectively, had prognostic value in the PDAC-only cohort. Similarly, mutations in key genes or well-described miRNA lost their prognostic significance in the PDAC-only cohort. Therefore, we propose a web-based application to assess biomarkers in the curated TCGA_PAAD dataset. In conclusion, TCGA_PAAD curation is critical to avoid important biological and clinical biases from non-PDAC samples.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Meng Cao ◽  
Peng-Bo Zhang ◽  
Peng-Fei Wu ◽  
Qun Chen ◽  
Wan-Li Ge ◽  
...  

DUOX2 has been reported to highly express in several types of cancers. However, the prognostic significance and the biological function of DUOX2 expression with pancreatic cancer (PC) still remain unclear. The present study is aimed at investigating whether DUOX2 could act as a novel biomarker of prognosis and evaluating its effect on PC cell progression. The mRNA and protein expression of DUOX2 in PC cells and tissues were assessed by quantitative real-time PCR (RT-qPCR) and immunohistochemistry. The effect of DUOX2 expression on PC cell motility and proliferation was evaluated in vitro. The correlation between DUOX2 mRNA expression and clinicopathological features and its prognostic significance were analyzed according to the Gene Expression Profiling Interactive Analysis (GEPIA) website based on The Cancer Genome Atlas (TCGA) and the GTEx databases combined with our clinical information. According to bioinformatics analysis, we forecasted the upstream transcription factors (TFs) and microRNA (miRNA) regulatory mechanism of DUOX2 in PC. The expression of DUOX2 at transcriptional and protein level was dramatically increased in PC specimens when compared to adjacent nontumor specimens. Functionally, DUOX2 knockdown inhibited cell motility and proliferation activities. Our clinical data revealed that the patients had better postoperative overall survival (OS) with lower expression of DUOX2, which is consistent with GEPIA data. Multivariate analysis revealed that high DUOX2 expression was considered as an independent prognostic indicator for OS ( P = 0.031 ). Based on Cistrome database, the top 5 TFs of each positively and negatively association with DUOX2 were predicted. hsa-miR-5193 and hsa-miR-1343-3p targeting DUOX2 were forecasted from TargetScan, miRDB, and DIANA-TarBase databases, which were negatively correlated with OS ( P = 0.043 and P = 0.0088 , respectively) and DUOX2 expression ( P = 0.0093 and P = 0.0032 , respectively) in PC from TCGA data. These findings suggest that DUOX2 acts as a promising predictive biomarker and an oncogene in PC, which could be a therapeutic target for PC.


Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 217-223
Author(s):  
Xin Song ◽  
Shidong Zhang ◽  
Run Tian ◽  
Chuanjun Zheng ◽  
Yuge Xu ◽  
...  

Abstract Background CKLF Like Marvel Transmembrane Domain Containing 1 (CMTM1) plays a role in breast cancer and lung cancer, but studies on the occurrence and development of CMTM1 in hepatocellular carcinoma (HCC) have not been reported. Methods The Cancer Genome Atlas (TCGA) database and immunohistochemistry (IHC) were used to detect CMTM1 expression in HCC tissues. The relationship between CMTM1 expression and the clinicopathological characteristics of HCC patients was analyzed by chi-square test, and the relationship between CMTM1 expression and the prognosis of HCC patients was tested by the Kaplan–Meier model. Results Bioinformatics analysis showed that the mRNA expression of CMTM1 was upregulated in HCC tissues, and low expression of CMTM1 is associated with longer disease-free survival in patients with HCC. Similarly, the survival time of HCC patients in CMTM1 high expression group was significantly shorter than that in CMTM1 low expression group. IHC detection indicated that CMTM1 protein was highly expressed in both HCC and adjacent non-tumor tissues, with a positive expression in 84% (63/75) of HCC tissues and 89.3% (67/75) of adjacent non-tumor tissues. Moreover, CMTM1 expression was related to family history and TNM stage of HCC patients (P < 0.05), but had no relationship with other clinicopathological characteristics. The survival analysis based on IHC results showed that the prognosis of HCC patients in CMTM1 negative group was significantly poorer than that in CMTM1 positive group (P < 0.05). Conclusion CMTM1 has a high expression in HCC tissues and is related to the prognosis of HCC patients.


2021 ◽  
Vol 11 ◽  
Author(s):  
Guo Zu ◽  
Jiacheng Gao ◽  
Tingting Zhou

BackgroundThe clinicopathological and prognostic significance of SRY-box transcription factor 9 (SOX9) expression in gastric cancer (GC) patients is still controversial. Our aim is to investigate the clinicopathological and prognostic value of SOX9 expression in GC patients.MethodsA systemic literature search and meta-analysis were used to evaluate the clinicopathological significance and overall survival (OS) of SOX9 expression in GC patients. The Cancer Genome Atlas (TCGA) dataset was used to investigate the relationship between SOX9 expression and OS of stomach adenocarcinoma (STAD) patients.ResultsA total of 11 articles involving 3,060 GC patients were included. In GC patients, the SOX9 expression was not associated with age [odds ratio (OR) = 0.743, 95% CI = 0.507–1.089, p = 0.128], sex (OR = 0.794, 95% CI = 0.605–1.042, p = 0.097), differentiation (OR = 0.728, 95% CI = 0.475–1.115, p = 0.144), and lymph node metastasis (OR = 1.031, 95% CI = 0.793–1.340, p = 0.820). SOX9 expression was associated with depth of invasion (OR = 0.348, 95% CI = 0.247–0.489, p = 0.000) and TNM stage (OR = 0.428, 95% CI = 0.308–0.595, p = 0.000). The 1-year OS (OR = 1.507, 95% CI = 1.167–1.945, p = 0.002), 3-year OS (OR = 1.482, 95% CI = 1.189–1.847, p = 0.000), and 5-year OS (OR = 1.487, 95% CI = 1.187–1.862, p = 0.001) were significantly shorter in GC patients with high SOX9 expression. TCGA analysis showed that SOX9 was upregulated in STAD patients compared with that in normal patients (p &lt; 0.001), and the OS of STAD patients with a high expression of SOX9 is poorer than that in patients with low expression of SOX9, but the statistical difference is not obvious (p = 0.31).ConclusionSOX9 expression was associated with the depth of tumor invasion, TNM stage, and poor OS of GC patients. SOX9 may be a potential prognostic factor for GC patients but needs further study.Systematic Review RegistrationPROSPERO, ID NUMBER 275712.


2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.


Author(s):  
Lei Feng ◽  
Jieqing Wang ◽  
Jianmin Zhang ◽  
Jingfang Diao ◽  
Longguang He ◽  
...  

Pancreatic cancer is one of the major malignancies and causes of mortality worldwide. E3 ubiquitin–protein ligases transfer activated ubiquitin from ubiquitin-conjugating enzymes to protein substrates and confer substrate specificity in cancer. In this study, we first downloaded data from The Cancer Genome Atlas pancreatic adenocarcinoma dataset, acquired all 27 differentially expressed genes (DEGs), and identified genomic alterations. Then, the prognostic significance of DEGs was analyzed, and eight DEGs (MECOM, CBLC, MARCHF4, RNF166, TRIM46, LONRF3, RNF39, and RNF223) and two clinical parameters (pathological N stage and T stage) exhibited prognostic significance. RNF223 showed independent significance as an unfavorable prognostic marker and was chosen for subsequent analysis. Next, the function of RNF223 in the pancreatic cancer cell lines ASPC-1 and PANC-1 was investigated, and RNF223 silencing promoted pancreatic cancer growth and migration. To explore the potential targets and pathways of RNF223 in pancreatic cancer, quantitative proteomics was applied to analyze differentially expressed proteins, and metabolism-related pathways were primarily enriched. Finally, the reason for the elevated expression of RNF223 was analyzed, and KLF4 was shown to contribute to the increased expression of RNF233. In conclusion, this study comprehensively analyzed the clinical significance of E3 ligases. Functional assays revealed that RNF223 promotes cancer by regulating cell metabolism. Finally, the elevated expression of RNF223 was attributed to KLF4-mediated transcriptional activation. This study broadens our knowledge regarding E3 ubiquitin ligases and signal transduction and provides novel markers and therapeutic targets in pancreatic cancer.


2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yong Joon Suh ◽  
Jung Ho Park ◽  
Sanchir-Erdene Bilegsaikhan ◽  
Dong Jin Lee

Prediction of malignant behavior of pheochromocytoma (PC) or paraganglioma (PG) is of limited value. The Cancer Genome Atlas (TCGA) and the French ‘Cortico et Médullosurrénale: les Tumeurs Endocrines’ (COMETE) network in Paris (France) facilitate accurate differentiation of malignant PC/PG based on genetic information. Therefore, the objective of this transcriptome analysis is to identify the prognostic genes underlying the differentiation of malignant PC/PG in the TCGA and COMETE databases. TCGA carries data pertaining to multigenomic analysis of 173 PC/PG surgical resection samples while the COMETE cohort contains data involving 188 PC/PG surgical resection samples. Clinical information and mRNA expression datasets were downloaded from TCGA and COMETE databases. Based on eligibility criteria, 58 of 173 PC/PG samples in TCGA and 171 of 188 PC/PG samples collected by the COMETE network were selected. Using Ingenuity Pathway Analysis, the mRNA expression of malignant and benign PC/PG was compared. The 58 samples in TCGA included 11 malignant and 47 benign cases. Among the 171 samples obtained from the COMETE cohort, 19 were malignant and 152 were benign. A comparative analysis of the mRNA expression data of the two databases revealed that 11 up/downregulated pathways involved in malignant PC/PG were related to cancer signaling, metabolic alteration, and prominent mitosis, whereas 6 upregulated genes and 1 downregulated gene were significantly enriched in the functional annotation pathways. The TCGA and COMETE databases showed differences in mRNA expression associated with malignant and benign PC/PG. Improved recognition of prognostic genes facilitates the diagnosis and treatment of PC/PG.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Fan Li ◽  
Weifeng Hu ◽  
Wei Zhang ◽  
Guohao Li ◽  
Yonglian Guo

Renal cell carcinoma (RCC), which was one of the most common malignant tumors in urinary system, had gradually increased incidence and mortality in recent years. Although significant advances had been made in molecular and biology research on the pathogenesis of RCC, effective treatments and prognostic indicators were still lacking. In order to predict the prognosis of RCC better, we identified 17 genes that were associated with the overall survival (OS) of RCC patients from The Cancer Genome Atlas (TCGA) dataset and a 17-gene signature was developed. Through SurvExpress, we analyzed the expression differences of the 17 genes and their correlation with the survival of RCC patients in five datasets (ZHAO, TCGA, KIPAN, KIRC, and KIRP), and then evaluated the survival prognostic significance of the 17-gene signature for RCC. Our results showed that the 17-gene signature had a predictive prognostic value not only in single pathologic RCC, but also in multiple pathologic types of RCC. In conclusion, the 17-gene signature model was related to the survival of RCC patients and could help predict the prognosis with significant clinical implications.


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