scholarly journals Screening and Identifying m6A Regulators as an Independent Prognostic Biomarker in Pancreatic Cancer Based on The Cancer Genome Atlas Database

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.

2020 ◽  
Author(s):  
Bi Lin ◽  
Hongwei Sun ◽  
Dinglai Yu ◽  
Yukai Xiang ◽  
Jie Zhang ◽  
...  

Abstract 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 portal (TCGA). 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. 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. 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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bai-Quan Qiu ◽  
Xia-Hui Lin ◽  
Song-Qing Lai ◽  
Feng Lu ◽  
Kun Lin ◽  
...  

Abstract Background Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study. Methods Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells. Results We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes. Conclusion Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.


Author(s):  
Xudong Tang ◽  
Mengyan Zhang ◽  
Liang Sun ◽  
Fengyan Xu ◽  
Xin Peng ◽  
...  

Long non-coding RNAs (lncRNAs) play key roles in tumors and function not only as important molecular markers for cancer prognosis, but also as molecular characteristics at the pan-cancer level. Because of the poor prognosis of pancreatic cancer, accurate assessment of prognosis is a key issue in the development of treatment plans for pancreatic cancer. Here we analyzed pancreatic cancer data from The Cancer Genome Atlas and The Genotype Tissue Expression database using Cox regression and lasso regression in analyses using a combination of the two databases as well as only The Cancer Genome Atlas database (Cancer Genome Atlas Research Network et al., 2013). A prognostic risk score model with significant correlation with pancreatic cancer survival was constructed, and two lncRNAs were investigated. Additional analysis of 33 cancers using the two lncRNAs showed that lncRNA TsPOAP1-AS1 was a prognostic marker of seven cancers, among which pancreatic cancer was the most significant, and lncRNA mi600hg was a prognostic marker of ovarian cancer and pancreatic cancer. LncRNA TsPOAP1-AS1 is associated with clinical stage and tumor mutation burden of some cancers as well as a strong degree of immune infiltration in many cancers, while a strong correlation between lncRNA mi600hg and microsatellite instability was observed in several cancers. The results of this study help further our understanding of the different functions of lncRNAs in cancer and may aid in the clinical application of lncRNAs as prognostic factors for cancer.


2019 ◽  
Vol 16 (3) ◽  
pp. 217-230
Author(s):  
Nurdina CHARONG ◽  
Moltira PROMKAN

ST7 (Suppression of Tumorigenicity 7) was reported as a protein playing a role in maintaining cellular structure. This study aims to investigate the ST7 alteration profiles and frequency of alteration in different cancers using data from The Cancer Genome Atlas (TCGA). The correlation between alterations of ST7 and angiogenesis-related genes, SERPINE1, MMP13, and VEGFA, was determined and the relation between ST7 and genes involved in suppression of ST7 transcription, PRMT5 and SMARCA4, were also analyzed. Data of 6 cancer groups from The Cancer Genome Atlas (TCGA) including ovarian serous cystadenocarcinoma (OSC), liver hepatocellular carcinoma (LHC), bladder urothelial adenocarcinoma (BUA), stomach adenocarcinoma (SC), prostate adenocarcinoma (PRAD) and glioblastoma multiforme (GBM) were downloaded for this study. The results indicated that 3 alteration patterns including amplification, missense mutation, and deletion were observed in 6 cancer studies. Gene pair between ST7 and SERPINE1 indicated the co-occurrent alteration in BUC, OSC and SC (p < 0.05). However, no association between alterations of these 2 genes and survival events in our study was observed. Shorter overall survival rate and disease-free survival were found in BUC patients with ST7, PRMT5, and  SMARCA4 alterations. These findings suggest that using TCGA data can target the potential genes involved in carcinogenesis. Combining ST7 with PRMT5 and SMARCA4 could be used as indicators for analyzing the patient survival in BUC patients and may serve as the potential therapeutic target for cancer in the future.


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.


Epigenomics ◽  
2021 ◽  
Author(s):  
Junyu Huo ◽  
Liqun Wu ◽  
Yunjin Zang

Aims: To investigate the prognostic significance of hypoxia- and ferroptosis-related genes for gastric cancer (GC). Materials & methods: We extracted data on 259 hypoxia- and ferroptosis-related genes from The Cancer Genome Atlas and identified the differentially expressed genes between normal (n = 32) and tumor (n = 375) tissues. A risk score was established by univariate Cox regression analysis and LASSO penalized Cox regression analysis. Results: The risk score contained eight genes showed good performance in predicting overall survival and relapse-free survival in GC patients in both the training cohort (The Cancer Genome Atlas, n = 350) and the testing cohorts (GSE84437, n = 431; GSE62254, n = 300; GSE15459, n = 191; GSE26253, n = 432). Conclusion: The eight-gene signature may help to the improve the prognostic risk classification of GC.


2020 ◽  
Vol 10 (8) ◽  
pp. 1189-1196
Author(s):  
Kaikai Ren ◽  
Jiakang Ma ◽  
Bo Zhou ◽  
Xiaoyan Lin ◽  
Mingyu Hou ◽  
...  

Hepatocellular carcinoma (HCC) is a malignancy originating from hepatocytes with a high rate of distant metastasis and recurrence. HCC prognosis remains poorly understood, although its diagnosis and treatment have improved globally. Therefore, it is necessary to identify reliable predictive and prognostic indicators of HCC. HCC gene expression profiles and corresponding clinical data were downloaded from The Cancer Genome Atlas. Seven lncRNAs (C10orf91, AC011352.3, AC015722.2, AC006372.1, PICSAR, AC110285.3, and AP001972.4) associated with immune and clinicopathological features were identified as biomarker candidates for HCC prognosis based on single-sample gene set enrichment analysis, the ESTIMATE algorithm, and Cox PHR analyses. Altogether, the findings revealed that the seven immune-related lncRNAs may provide a reference for improving HCC prognosis.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Henriette Huschka ◽  
Sabine Mihm

Abstract Background Hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC) are malignancies with a leading lethality. With reference to interferons (IFNs) known to mediate antitumor activities, this study investigated the relationship between germline genetic variations in type III IFN genes and cancer disease progression from The Cancer Genome Atlas (TCGA) data. The genetic variations under study tag a gain-or-loss-of-function dinucleotide polymorphism within the IFNL4 gene, rs368234815 [TT/ΔG]. Methods The entirety of the TCGA sequencing data was used to assess genotypes of 187 patients with HCC and of 162 patients with PDAC matched for ethnicity. Stratified for IFNL genotypes, both cohorts were subjected to time-to-event analyses according to Kaplan-Meier with regard to the length of the specific progression free interval (PFI) and the overall survival (OS) time as two clinical endpoints for disease progression. Results Logrank analysis revealed a significant relationship between IFNL genotypes and disease outcome for PDAC. This relationship was not found for HCC. A multiple Cox regression analysis employing patients’ age, tumor grade and tumor stage as further covariates proved IFNL genotypes to be independent predictors for PDAC disease outcome. Conclusion This repository-based approach unveiled clinical evidence suggestive for an impact of IFNL germline variations for PDAC progression with an IFNL haplotype predisposing for IFNL4 expression being favorable.


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