scholarly journals Transcriptome Analysis Reveals Significant Differences in Gene Expression of Malignant Pheochromocytoma or Paraganglioma

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.

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 662
Author(s):  
Mario Mischkulnig ◽  
Barbara Kiesel ◽  
Daniela Lötsch ◽  
Thomas Roetzer ◽  
Martin Borkovec ◽  
...  

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.


2020 ◽  
Vol 16 (1) ◽  
pp. 4279-4288 ◽  
Author(s):  
Qiangwei Wang ◽  
Zhiliang Wang ◽  
Zhaoshi Bao ◽  
Chuanbao Zhang ◽  
Zheng Wang ◽  
...  

Aim: We aimed at investigating molecular features and potential clinical value of PABPC1 in gliomas. Materials & methods: We assembled totally 1000 glioma samples with mRNA expression data from Chinese Glioma Genome Atlas and The Cancer Genome Atlas. We utilized R language as the main analysis tool. Gene Ontology was performed for functional analysis. Results: PABPC1 was downregulated in gliomas with higher malignance and PABPC1 may contribute as potential predictor of proneural subtype in gliomas. Higher expression of PABPC1 was significantly related to better prognosis and related to biological process of translation. Conclusion: Our finding improves the understanding of PABPC1 as a novel biomarker with potential therapeutic connotations.


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.


2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Rui-min Ma ◽  
Fan Yang ◽  
Du-ping Huang ◽  
Min Zheng ◽  
Yi-luan Wang

Aim. To investigate the mRNA expression and clinical significance of structural maintenance of chromosomes protein 4 (SMC4) in breast cancer. Methods. A total of 23 paired samples were sequenced, and data from the Cancer Genome Atlas were analyzed. Results. SMC4 mRNA level was significantly upregulated in breast cancer tissues (P<0.001). Patients with high mRNA expression of SMC4 had significantly poor survival (P=0.012). Subgroup analyses show that in nontriple negative breast cancer (non-TNBC) patients, the high SMC4 mRNA expression, older age (>65), negative progesterone receptor, and advanced stages (III-IV) were independent risk factors (HR=3.293, 95% CI 1.257-8.625, P=0.015). In patients with TNBC, high mRNA expression of SMC4 correlated with better survival rate (P<0.046). Conclusion. SMC4 mRNA level is a good prognostic biomarker for patients with breast cancer.


2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 537-537
Author(s):  
Yasuhiro Hashimoto ◽  
Hayato Yamamoto ◽  
Shingo Hatakeyama ◽  
Takahiro Yoneyama ◽  
Chikara Ohyama

537 Background: Programmed cell death ligand-1 (PD-L1) is a key target molecule of immunotherapy that is frequently overexpressed in several neoplasms. But there were few reports about PD-L1 expression of pheochromocytoma. In the present study, we examined PD-L1 expression in pheochromocytoma. Methods: PD-L1 mRNA expression was compared across 184 pheochromocytoma, 492 prostate cancer cases and 404 bladder cancer cases based on The Cancer Genome Atlas (TCGA). Furthermore, we enrolled 32 pheochromocytoma patients treated with surgery at our hospital between June 2005 and February 2016. We conducted an immunohistochemistry (IHC) of PD-L1 using the SP142 assay. PD-L1 expression was scored at three diagnostic levels (0/1/2). Results: Comparison of PD-L1 mRNA expression based on the TCGA revealed that PD-L1 expression was significantly higher in pheochromocytoma than in bladder cancer and in prostate cancer (p < 0.001). In the SP 142 assay of our 32 pheochromocytoma, the prevalence of positive PD-L1 expression (IHC score 1 or 2 (1/2)) in tumor-infiltrating immune cells (TICs) was 8 patients (25%). The prevalence of positive PD-L1 expression in tumor cells (TCs) was 9 patients (28.1%). Tumor diameter of PD-L1 (+) in TICs patients was 3.36±0.35 cm and that of PD-L1 (-) in TCs patients was 5.37±0.50cm, there was statistically significance between two groups. (unpaired t test: p=0.044) In our cohort, there were two malignant pheochromocytoma. But there were not PD-L1 positive cases in malignant pheochromocytoma. Conclusions: PD-L1 expression is relatively high in pheochromocytoma compared to bladder cancer and prostate cancer based on TCGA. In the SP142 assay of our 32 pheochromocytoma cases, tumor diameter of PD-L1 (-) in TICs cases was larger than that of PD-L1 (+) cases. In our cohort, there were not PD-L1 (+) cases in malignant pheochromocytoma. These findings suggest that PD-L1 expression of pheochromocytoma was comparatively common and PD-L1 positive expression of pheochromocytoma may not be associated with tumor aggressiveness.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Nicole Pinto ◽  
Morgan Black ◽  
Krupal Patel ◽  
John Yoo ◽  
Joe S. Mymryk ◽  
...  

Thyroid cancer is an endocrine malignancy with an incidence rate that has been increasing steadily over the past 30 years. While well-differentiated subtypes have a favorable prognosis when treated with surgical resection and radioiodine, undifferentiated subtypes, such as anaplastic thyroid cancer (ATC), are far more aggressive and have a poor prognosis. Conventional therapies (surgical resection, radiation, chemotherapy, and radioiodine) have been utilized for treatment of ATC, yet these treatments have not significantly improved the overall mortality rate. As cancer is a genetic disease, genetic alterations such as mutations, fusions, activation of oncogenes, and silencing of tumor suppressors contribute to its aggressiveness. With the use of next-generation sequencing and the Cancer Genome Atlas, mutation-directed therapy is recognized as the upcoming standard of care. In this review, we highlight the known genetic landscape of ATC and the need for a comprehensive genetic characterization of this disease in order to identify additional therapeutic targets to improve patient outcomes.


Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3609
Author(s):  
Bing-Ze Lin ◽  
Shen-Ying Wan ◽  
Min-Ying Lin ◽  
Chih-Hsien Chang ◽  
Ting-Wen Chen ◽  
...  

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.


2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Cheng Zhang ◽  
Chunlin Ge

Background. Cholangiocarcinoma (CCA) is the second most common malignant primary liver tumor and has shown an alarming increase in incidence over the last two decades. However, the mechanisms behind tumorigenesis and progression remain insufficient. The present study aimed to uncover the underlying regulatory mechanism on CCA and find novel biomarkers for the disease prognosis. Method. The RNA-sequencing (RNA-seq) datasets of lncRNAs, miRNAs, and mRNAs in CCA as well as relevant clinical information were obtained from the Cancer Genome Atlas (TCGA) database. After pretreatment, differentially expressed RNAs (DERNAs) were identified and further interrogated for their correlations with clinical information. Prognostic RNAs were selected using univariate Cox regression. Then, a ceRNA network was constructed based on these RNAs. Results. We identified a total of five prognostic DEmiRNAs, 63 DElncRNAs, and 90 DEmRNAs between CCA and matched normal tissues. Integrating the relationship between the different types of RNAs, an lncRNA-miRNA-mRNA network was established and included 28 molecules and 47 interactions. Screened prognostic RNAs involved in the ceRNA network included 3 miRNAs (hsa-mir-1295b, hsa-mir-33b, and hsa-mir-6715a), 7 lncRNAs (ENSG00000271133, ENSG00000233834, ENSG00000276791, ENSG00000241155, COL18A1-AS1, ENSG00000274737, and ENSG00000235052), and 18 mRNAs (ANO9, FUT4, MLLT3, ABCA3, FSCN2, GRID2IP, NCK2, MACC1, SLC35E4, ST14, SH2D3A, MOB3B, ACTL10, RAB36, ATP1B3, MST1R, SEMA6A, and SEL1L3). Conclusions. Our study identified novel prognostic makers and predicted a previously unknown ceRNA regulatory network in CCA and may provide novel insight into a further understanding of lncRNA-mediated ceRNA regulatory mechanisms in CCA.


2021 ◽  
Vol 22 (4) ◽  
pp. 2134
Author(s):  
Liting Huang ◽  
Jie Zhu ◽  
Weikaixin Kong ◽  
Peifeng Li ◽  
Sujie Zhu

Colon cancer is a common and leading cause of death and malignancy worldwide. N6-methylation of adenosine (m6A) is the most common reversible mRNA modification in eukaryotes, and it plays a crucial role in various biological functions in vivo. Dysregulated expression and genetic changes of m6A regulators have been correlated with tumorigenesis, cancer cell proliferation, tumor microenvironment, and prognosis in cancers. This study used RNA-seq and colon cancer clinical data to explore the relationship between N6-methylation and colon cancer. Based on the seven m6A regulators related to prognosis, three molecular subgroups of colon cancer were identified. Surprisingly, we found that each subgroup had unique survival characteristics. We then identified three subtypes of tumors based on 299 m6A phenotype-related genes, and one subtype was characterized as an immunosuppressive tumor and patients in this subtype may be more suitable for immunotherapy than other subtypes. Finally, using m6A-related genes and clinical information from The Cancer Genome Atlas cohort, we constructed a prognosis model, and this model could be used to predict the prognosis of patients in clinics.


2021 ◽  
Vol 11 ◽  
Author(s):  
Rodolfo Bortolozo Serafim ◽  
Patrick da Silva ◽  
Cibele Cardoso ◽  
Luis Fernando Macedo Di Cristofaro ◽  
Renato Petitto Netto ◽  
...  

Glioblastoma (GBM) is the most lethal and frequent type of brain tumor, leading patients to death in approximately 14 months after diagnosis. GBM treatment consists in surgical removal followed by radio and chemotherapy. However, tumors commonly relapse and the treatment promotes only a slight increase in patient survival. Thus, uncovering the cellular mechanisms involved in GBM resistance is of utmost interest, and the use of cell lines has been shown to be an extremely important tool. In this work, the exploration of RNAseq data from different GBM cell lines revealed different expression signatures, distinctly correlated with the behavior of GBM cell lines regarding proliferation indexes and radio-resistance. U87MG and U138MG cells, which presented expressively reduced proliferation and increased radio-resistance, showed a particular expression signature encompassing enrichment in many extracellular matrix (ECM) and receptor genes. Contrasting, U251MG and T98G cells, that presented higher proliferation and sensibility to radiation, exhibited distinct signatures revealing consistent enrichments for DNA repair processes and although several genes from the ECM-receptor pathway showed up-regulation, enrichments for this pathway were not detected. The ECM-receptor is a master regulatory pathway that is known to impact several cellular processes including: survival, proliferation, migration, invasion, and DNA damage signaling and repair, corroborating the associations we found. Furthermore, searches to The Cancer Genome Atlas (TCGA) repository revealed prognostic correlations with glioma patients for the majority of genes highlighted in the signatures and led to the identification of 31 ECM-receptor genes individually correlated with radiation responsiveness. Interestingly, we observed an association between the number of upregulated genes and survivability greater than 5 years after diagnosis, where almost all the patients that presented 21 or more upregulated genes were deceased before 5 years. Altogether our findings suggest the clinical relevance of ECM-receptor genes signature found here for radiotherapy decision and as biomarkers of glioma prognosis.


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