scholarly journals Characterization of bidirectional gene pairs in The Cancer Genome Atlas (TCGA) dataset

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7107 ◽  
Author(s):  
Juchuanli Tu ◽  
Xiaolu Li ◽  
Jianjun Wang

The “bidirectional gene pair” indicates a particular head-to-head gene organization in which transcription start sites of two genes are located on opposite strands of genomic DNA within a region of one kb. Despite bidirectional gene pairs are well characterized, little is known about their expression profiles and regulation features in tumorigenesis. We used RNA-seq data from The Cancer Genome Atlas (TCGA) dataset for a systematic analysis of the expression profiles of bidirectional gene pairs in 13 cancer datasets. Gene pairs on the opposite strand with transcription end site distance within one kb or on the same strand with the distance of two genes between 1–10 kb and gene pairs comprising two randomly chosen genes were used as control gene pairs (CG1, CG2, and random). We identified and characterized up-/down-regulated genes by comparing the expression level between tumors and adjacent normal tissues in 13 TCGA datasets. There were no consistently significant difference in the percentage of up-/down-regulated genes between bidirectional and control/random genes in most of TCGA datasets. However, the percentage of bidirectional gene pairs comprising two up- or two down-regulated genes was significantly higher than gene pairs from CG1/2 in 12/11 analyzed TCGA datasets and the random gene pairs in all 13 TCGA datasets. Then we identified the methylation correlated bidirectional genes to explore the regulatory mechanism of bidirectional genes. Like the differentially expressed gene pairs, the bidirectional genes in a pair were significantly prone to be both hypo- or hyper-methylation correlated genes in 12/13 TCGA datasets when comparing to the CG2/random gene pairs despite no significant difference between the percentages of hypo-/hyper-methylation correlated genes in bidirectional and CG2/random genes in most of TCGA datasets. Finally, we explored the correlation between bidirectional genes and patient’s survival, identifying prognostic bidirectional genes and prognostic bidirectional gene pairs in each TCGA dataset. Remarkably, we found a group of prognostic bidirectional gene pairs in which the combination of two protein coding genes with different expression level correlated with different survival prognosis in survival analysis for OS. The percentage of these gene pairs in bidirectional gene pair were significantly higher than the gene pairs in controls in COAD datasets and lower in none of 13 TCGA datasets.

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Bi Lin ◽  
Yangyang Pan ◽  
Dinglai Yu ◽  
Shengjie Dai ◽  
Hongwei Sun ◽  
...  

Background. Pancreatic cancer is one of the most malignant tumors of the digestive system, and its treatment has rarely progressed for the last two decades. Studies on m6A regulators for the past few years have seemingly provided a novel approach for malignant tumor therapy. m6A-related factors may be potential biomarkers and therapeutic targets. This research is focused on the gene characteristics and clinical values of m6A regulators in predicting prognosis in pancreatic cancer. Methods. In our study, we obtained gene expression profiles with copy number variation (CNV) data and clinical characteristic data of 186 patients with pancreatic cancer from The Cancer Genome Atlas (TCGA) portal. Then, we determined the alteration of m6a regulators and their correlation with clinicopathological features using the log-rank tests, Cox regression model, and chi-square test. Additionally, we validated the prognostic value of m6A regulators in the International Cancer Genome Consortium (ICGC). Results. The results suggested that pancreatic cancer patients with ALKBH5 CNV were associated with worse overall survival and disease-free survival than those with diploid genes. Additionally, upregulation of the writer gene ALKBH5 had a positive correlation with the activation of AKT pathways in the TCGA database. Conclusion. Our study not only demonstrated genetic characteristic changes of m6A-related genes in pancreatic cancer and found a strong relationship between the changes of ALKBH5 and poor prognosis but also provided a novel therapeutic target for pancreatic cancer therapy.


2014 ◽  
Vol 36 (4) ◽  
pp. E23 ◽  
Author(s):  
David D. Gonda ◽  
Vincent J. Cheung ◽  
Karra A. Muller ◽  
Amit Goyal ◽  
Bob S. Carter ◽  
...  

Differentiating between low-grade gliomas (LGGs) of astrocytic and oligodendroglial origin remains a major challenge in neurooncology. Here the authors analyzed The Cancer Genome Atlas (TCGA) profiles of LGGs with the goal of identifying distinct molecular characteristics that would afford accurate and reliable discrimination of astrocytic and oligodendroglial tumors. They found that 1) oligodendrogliomas are more likely to exhibit the glioma-CpG island methylator phenotype (G-CIMP), relative to low-grade astrocytomas; 2) relative to oligodendrogliomas, low-grade astrocytomas exhibit a higher expression of genes related to mitosis, replication, and inflammation; and 3) low-grade astrocytic tumors harbor microRNA profiles similar to those previously described for glioblastoma tumors. Orthogonal intersection of these molecular characteristics with existing molecular markers, such as IDH1 mutation, TP53 mutation, and 1p19q status, should facilitate accurate and reliable pathological diagnosis of LGGs.


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