scholarly journals Comprehensive Analysis of the Expression of Sodium/Potassium-ATPase α Subunits and Prognosis of Ovarian Serous Cystadenocarcinoma

2020 ◽  
Author(s):  
Wei Huang ◽  
Yongjian Zhang ◽  
Ye Xu ◽  
Shaoyou Yang ◽  
Bing Li ◽  
...  

Abstract Background: Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide; however, biomarkers to diagnose and predict prognosis of OSC remain limited. Therefore, the present study aimed to investigate whether sodium/potassium adenosine triphosphate (Na+/K+-ATP)ase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC.Methods: Gene expression data (RNA-Seq) of 376 patients with OSC were downloaded from The Cancer Genome Atlas (TCGA) program database. Additional databases used in our analysis included the Gene Expression Omnibus, International Cancer Genome Consortium, Genotype–Tissue Expression, the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia.Results: The expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression levels of ATP1A2 and ATP1A4 were lower in OSC tissues than in normal ovarian tissues. Overexpression of ATP1A2 was significantly associated with a higher Federation of Gynecology and Obstetrics (FIGO) stage and histological grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in patients with OSC, whereas higher expression of ATP1A4 was associated with favorable OS and DSS. Multivariate analysis showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS in patients with OSC. Moreover, ATP1A1 staining was abundant in tumor tissues. A high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years and with FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As were 3%–5%.Conclusions: These results indicate that the ATP1A gene family could be potential diagnostic or prognostic markers of OSC. In addition, ATP1As may be effective therapeutic targets in the treatment of OSC.

2020 ◽  
Author(s):  
Wei Huang ◽  
Yongjian Zhang ◽  
Ye Xu ◽  
Shaoyou Yang ◽  
Bing Li ◽  
...  

Abstract Background Ovarian serous cystadenocarcinoma (OSC) is the most common and lethal gynecological cancer in women worldwide. Biomarkers to diagnose and predict prognosis of OSC remain limited. We therefore aimed to investigate whether Na+/K+-ATPase α-subunits (ATP1As) are helpful diagnostic and prognostic markers of OSC. Methods Gene expression data (RNA-Seq) of 376 patients with ovarian serous cystadenocarcinoma were downloaded from The Cancer Genome Atlas (TCGA) program database. Further databases used in our analysis included Genotype-Tissue Expression (GTEx), the Human Protein Atlas, cBioPortal for Cancer Genomics, and Cancer Cell Line Encyclopedia (CCLE). Results Expression levels of ATP1A1 and ATP1A3 were higher in OSC tissues than in normal ovarian tissues, whereas the expression level of ATP1A2 and ATP1A4 were lower in the former than in the latter. Overexpression of ATP1A2 was significantly associated with higher Federation of Gynecology and Obstetrics (FIGO) stage and histologic grade. Increased mRNA expression of ATP1A3 was significantly associated with shorter overall survival (OS) and disease-specific survival (DSS) in OSC patients, while greater ATP1A4 levels were associated with favorable OS and DSS. Multivariate analysis also showed that primary therapy outcome, residual tumor, and mRNA expressions of ATP1A3 and ATP1A4 were independent prognostic factors for both OS and DSS of OSC patients. Moreover, ATP1A1 staining was abundant in tumor tissues. Furthermore, a high expression of ATP1A3 was significantly correlated with poor OS and DSS in the subgroup of patients aged ≥ 60 years, FIGO stage III, histological grade G3, and TP53 mutation. Mutation frequencies of the ATP1As ranged 3%-5%. Conclusions In conclusion, these results indicate that the ATP1As gene family could be potential diagnostic or prognostic markers for OSC. In addition, ATP1As may be effective therapeutic targets for the treatment of OSC.


2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Xiaofei Wang ◽  
Jie Qiao ◽  
Rongqi Wang

Abstract The present study aimed to construct a novel signature for indicating the prognostic outcomes of hepatocellular carcinoma (HCC). Gene expression profiles were downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) databases. The prognosis-related genes with differential expression were identified with weighted gene co-expression network analysis (WGCNA), univariate analysis, the least absolute shrinkage and selection operator (LASSO). With the stepwise regression analysis, a risk score was constructed based on the expression levels of five genes: Risk score = (−0.7736* CCNB2) + (1.0083* DYNC1LI1) + (−0.6755* KIF11) + (0.9588* SPC25) + (1.5237* KIF18A), which can be applied as a signature for predicting the prognosis of HCC patients. The prediction capacity of the risk score for overall survival was validated with both TCGA and ICGC cohorts. The 1-, 3- and 5-year ROC curves were plotted, in which the AUC was 0.842, 0.726 and 0.699 in TCGA cohort and 0.734, 0.691 and 0.700 in ICGC cohort, respectively. Moreover, the expression levels of the five genes were determined in clinical tumor and normal specimens with immunohistochemistry. The novel signature has exhibited good prediction efficacy for the overall survival of HCC patients.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Chuanhui Sun ◽  
Changsong Han ◽  
Peng Wang ◽  
Yinji Jin ◽  
Yanan Sun ◽  
...  

The purpose of this study was to investigate the HOX gene expression profile in laryngeal squamous cell carcinoma (LSCC) and assess whether some genes are associated with the clinicopathological features and prognosis in LSCC patients. The HOX gene levels were tested by microarray and validated by qRT-PCR in paired cancerous and adjacent noncancerous LSCC tissue samples. The microarray testing data of 39 HOX genes revealed 15 HOX genes that were at least 2-fold upregulated and 2 that were downregulated. After qRT-PCR evaluation, the three most upregulated genes (HOXB9, HOXB13, and HOXD13) were selected for tissue microarray (TMA) analysis. The correlations between the HOXB9, HOXB13, and HOXD13 expression levels and both clinicopathological features and prognosis were analyzed. Three HOX gene expression levels were markedly increased in LSCC tissues compared with adjacent noncancerous tissues (P<0.001). HOXB9 was found to correlate with histological grade (P<0.01) and prognosis (P<0.01) in LSCC. In conclusion, this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in LSCC. Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients.


2020 ◽  
Author(s):  
Ji Yun Lee ◽  
Joo Hyun Kim ◽  
Heejin Bang ◽  
Junhun Cho ◽  
Young Hyeh Ko ◽  
...  

Abstract Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI, 13.0–69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.


Blood ◽  
2011 ◽  
Vol 118 (22) ◽  
pp. 5905-5913 ◽  
Author(s):  
Anna Staffas ◽  
Meena Kanduri ◽  
Randi Hovland ◽  
Richard Rosenquist ◽  
Hans Beier Ommen ◽  
...  

Abstract Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ji Yun Lee ◽  
Joo Hyun Kim ◽  
Heejin Bang ◽  
Junhun Cho ◽  
Young Hyeh Ko ◽  
...  

AbstractExtranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI 13.0–69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hao Zhang ◽  
Renzheng Liu ◽  
Lin Sun ◽  
Xiao Hu

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. This study aimed to establish a reliable prognostic model for HCC using histological grades and the expression levels of related genes. The histological grade of a tumor provides prognostic information. The expression data of HCC samples were downloaded from The Cancer Genome Atlas (TCGA) database. We employed the univariate and multivariate Cox regression analyses, as well as the least absolute shrinkage and selection operator (LASSO) regression to establish the prognostic model. After verification of the proposed model using data downloaded from the International Cancer Genome Consortium (ICGC) database, we found that the model was highly reliable, and it was revealed that the prognosis in the high-risk group was significantly worse than that in the low-risk group. Next, we explored the correlation of RiskScore with patients’ clinicopathological characteristics, and we found that the RiskScore could be used as an independent prognostic factor, which further confirmed the reliability of our model. In summary, the proposed model could accurately predict the prognosis of HCC patients, assisting clinicians to study the roles of different histological grades of HCC.


2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Carlos Henrique Foncesca Peiró ◽  
Jéssica Freitas Araújo Encinas ◽  
Glauco Sérgio Avelino Aquino ◽  
Glaucia Luciano Veiga ◽  
Matheus Moreira Perez ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Weiting Kang ◽  
Meng Zhang ◽  
Qiang Wang ◽  
Da Gu ◽  
Zhilong Huang ◽  
...  

Clear cell renal cell carcinoma (ccRCC) is the most common lethal subtype of renal cancer, and changes in tumor metabolism play a key role in its development. Solute carriers (SLCs) are important in the transport of small molecules in humans, and defects in SLC transporters can lead to serious diseases. The expression patterns and prognostic values of SLC family transporters in the development of ccRCC are still unclear. The current study analyzed the expression levels of SLC family members and their correlation with prognosis in ccRCC patients with data from Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), The Cancer Genome Atlas (TCGA), cBioPortal, the Human Protein Atlas (HPA), the International Cancer Genome Consortium (ICGC), and the Gene Expression Omnibus (GEO). We found that the mRNA expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly lower in ccRCC tissues than in normal tissues and the protein expression levels of SLC22A6, SLC22A7, SLC22A13, and SLC34A1 were also significantly lower. Except for SLC22A7, the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were correlated with the clinical stage of ccRCC patients. The lower the expression levels of SLC22A6, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were, the later the clinical stage of ccRCC patients was. Further experiments revealed that the expression levels of SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 were significantly associated with overall survival (OS) and disease-free survival (DFS) in ccRCC patients. High SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 expression predicted improved OS and DFS. Finally, GSE53757 and ICGC were used to revalidate the differential expression and clinical prognostic value. This study suggests that SLC22A6, SLC22A7, SLC22A13, SLC25A4, SLC34A1, and SLC44A4 may be potential targets for the clinical diagnosis, prognosis, and treatment of ccRCC patients.


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