scholarly journals TRIM59: A potential diagnostic and prognostic biomarker in human tumors

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257445
Author(s):  
Zheng Jin ◽  
Liping Liu ◽  
Youran Yu ◽  
Dong Li ◽  
Xun Zhu ◽  
...  

TRIM59 is a protein that is highly expressed in a variety of tumors and promotes tumor development. However, the use of TRIM59 as tumor diagnosis and prognosis biomarker has not been fully explored. We collected datasets from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) to investigate its potential as a biomarker for diagnosis and prognosis. A total of 46 studies, including 11,558 patients were included in this study. Here, we showed that TRIM59 was significantly upregulated in 15 type of human solid tumors in comparison to their adjacent tissues. Receiver operating characteristic curve (ROC) results provided further evidence for the use of TRIM59 as a potential tumor diagnosis biomarker. Overall survival (OS) was compared between TRIM59 high expression and low expression groups. High expression of TRIM59 indicated a poor prognosis in multiple solid tumors. Taken together, these analyses showed that TRIM59 was upregulated in various types of tumors and had the potential to be used as a diagnostic and prognostic biomarker in human solid tumors.

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Shujie Ruan ◽  
Jingping Shi ◽  
Ming Wang ◽  
Zhechen Zhu

Plakophilins (PKPs) act as a key regulator of different signaling programs and control a variety of cellular processes ranging from transcription, protein synthesis, growth, proliferation, and tumor development. The function and possible mechanism of PKP3 in ovarian cancer (OC) remain unknown. It is extremely important to investigate the expression and prognostic values of PKP3, as well as their possible mechanisms, and immune infiltration in OC. Therefore, in this paper we explored the potential oncogenic role of PKP3 in 33 tumors based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The result outcomes showed that PKP3 is highly expressed in most cancers, and the expression level and prognosis of PKP3 showed little significance in cancer patients. Moreover, oncologists have found that members of the plakophilin family have different degrees of abnormality in ovarian cancer. PKP3 played a key part in carcinogenesis and aggressiveness of OC as well as malignant biological activity and can be used as a biomarker for early diagnosis and prognosis evaluation in OC.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Rui-kun Zhang ◽  
Jia-lin Liu

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and invasive malignant tumors in the world. The change in DNA methylation is a key event in HCC. Methods Methylation datasets for HCC and 17 other types of cancer were downloaded from The Cancer Genome Atlas (TCGA). The CpG sites with large differences in methylation between tumor tissues and paracancerous tissues were identified. We used the HCC methylation dataset downloaded from the TCGA as the training set and removed the overlapping sites among all cancer datasets to ensure that only CpG sites specific to HCC remained. Logistic regression analysis was performed to select specific biomarkers that can be used to diagnose HCC, and two datasets—GSE157341 and GSE54503—downloaded from GEO as validation sets were used to validate our model. We also used a Cox regression model to select CpG sites related to patient prognosis. Results We identified 6 HCC-specific methylated CpG sites as biomarkers for HCC diagnosis. In the training set, the area under the receiver operating characteristic (ROC) curve (AUC) for the model containing all these sites was 0.971. The AUCs were 0.8802 and 0.9711 for the two validation sets from the GEO database. In addition, 3 other CpG sites were analyzed and used to create a risk scoring model for patient prognosis and survival prediction. Conclusions Through the analysis of HCC methylation datasets from the TCGA and Gene Expression Omnibus (GEO) databases, potential biomarkers for HCC diagnosis and prognosis evaluation were ascertained.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jianlin Chen ◽  
Junping Ding ◽  
Wenjie Huang ◽  
Lin Sun ◽  
Jinping Chen ◽  
...  

Previous researches have highlighted that low-expressing deoxyribonuclease1-like 3 (DNASE1L3) may play a role as a potential prognostic biomarker in several cancers. However, the diagnosis and prognosis roles of DNASE1L3 gene in lung adenocarcinoma (LUAD) remain largely unknown. This research aimed to explore the diagnosis value, prognostic value, and potential oncogenic roles of DNASE1L3 in LUAD. We performed bioinformatics analysis on LUAD datasets downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analyzed with various online databases. We found that both the mRNA and protein levels of DNASE1L3 in patients with LUAD were noticeably lower than that in normal tissues. Low DNASE1L3 expression was significantly associated with higher pathological stages, T stages, and poor prognosis in LUAD cohorts. Multivariate analysis revealed that DNASE1L3 was an independent factor affecting overall survival (HR = 0.680, p = 0.027). Moreover, decreased DNASE1L3 showed strong diagnostic efficiency for LUAD. Results indicated that the mRNA level of DNASE1L3 was positively correlated with the infiltration of various immune cells, immune checkpoints in LUAD, especially with some m6A methylation regulators. In addition, enrichment function analysis revealed that the co-expressed genes may participate in the process of intercellular signal transduction and transmission. GSEA indicated that DNASE1L3 was positively related to G protein-coupled receptor ligand biding (NES = 1.738; P adjust = 0.044; FDR = 0.033) and G alpha (i) signaling events (NES = 1.635; P adjust = 0.044; FDR = 0.033). Our results demonstrated that decreased DNASE1L3 may serve as a novel diagnostic and prognostic biomarker associating with immune infiltrates in lung adenocarcinoma.


2021 ◽  
Vol 18 (2) ◽  
pp. 115-127
Author(s):  
Zhenxing Feng ◽  
Jiao Zhang ◽  
Yafang Zheng ◽  
Qingzhang Wang ◽  
Xiaochuan Min ◽  
...  

Aim: ASF1 is involved in tumorigenesis. However, its possible role in lung adenocarcinoma (LUAD) is unclear. This study thus explored the role of ASF1A and ASF1B in LUAD. Materials & methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus were employed to investigate ASF1A and ASF1B expression and its roles in LUAD prognosis. Immunohistochemistry was applied to determine the protein expression of ASF1B of 30 LUAD patients. Results: The upregulation of ASF1B in tumor tissues is associated with worse overall survival and progress-free survival and is correlated with advanced tumor stage and tumor development. However, aberrant expression of ASF1A was not found in LUAD and ASF1A was not related to patients’ overall survival and progress-free survival. Conclusion: ASF1B could be a promising prognostic and therapeutic biomarker in LUAD.


2018 ◽  
Vol 49 (1) ◽  
pp. 134-143 ◽  
Author(s):  
Cheng-Peng Yu ◽  
Shu-Fang Fu ◽  
Xuan Chen ◽  
Jing Ye ◽  
Yuan Ye ◽  
...  

Background/Aims: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme catalyzing the initial and rate-limiting steps in the kynurenine pathway, which converts tryptophan into kynurenine. Upregulation of IDO1 decreases tryptophan levels and increases the accumulation of kynurenine and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence has shown that IDO1 is highly expressed in various cancer types and associated with poor prognosis of cancer patients. However, the results were inconsistent. Methods: We searched the Web of Science, PubMed, Embase and Cochrane library databases to identify studies evaluating the prognostic value of IDO1 in cancer patients. Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using fixed-effects/random-effects models. Results: This systematic review and meta-analysis included 2706 patients from 24 articles. The results indicated a shorter overall survival in patients with high expression of IDO1 (hazard ratio [HR] = 2.03, 95% confidence interval [CI]: 1.56-2.63). Furthermore, disease-free survival was worse in patients with high expression of IDO1 (HR = 2.47, 95% CI: 1.46-4.20). Additionally, the pooled odds ratios (ORs) showed that increased IDO1 was significantly associated with tumor differentiation (OR = 1.81, 95% CI: 1.05-3.12), distant metastasis (OR = 1.45, 95% CI: 1.02-2.06), and poor clinical stage (OR = 1.89, 95% CI: 1.13-3.17). However, no significant correlation was observed of increased IDO1 expression with age, sex, lymph node metastasis, and tumor size. Conclusion: High expression of IDO1 is associated with poor clinical outcomes. IDO1 could serve as a biomarker of prognosis and a potential predictive factor of clinicopathology in various cancers. Further studies should be performed to verify the clinical utility of IDO1 in human solid tumors.


2020 ◽  
Vol 16 (3) ◽  
pp. 347-366 ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao

Abstract Reprogramming of metabolism is described in many types of cancer and is associated with the clinical outcomes. However, the prognostic significance of pyrimidine metabolism signaling pathway in lung adenocarcinoma (LUAD) is unclear. Using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets, we found that the pyrimidine metabolism signaling pathway was significantly enriched in LUAD. Compared with normal lung tissues, the pyrimidine metabolic rate–limiting enzymes were highly expressed in lung tumor tissues. The high expression levels of pyrimidine metabolic–rate limiting enzymes were associated with unfavorable prognosis. However, purinergic receptors P2RX1, P2RX7, P2RY12, P2RY13, and P2RY14 were relatively downregulated in lung cancer tissues and were associated with favorable prognosis. Moreover, we found that hypo-DNA methylation, DNA amplification, and TP53 mutation were contributing to the high expression levels of pyrimidine metabolic rate–limiting enzymes in lung cancer cells. Furthermore, combined pyrimidine metabolic rate–limiting enzymes had significant prognostic effects in LUAD. Comprehensively, the pyrimidine metabolic rate–limiting enzymes were highly expressed in bladder cancer, breast cancer, colon cancer, liver cancer, and stomach cancer. And the high expression levels of pyrimidine metabolic rate–limiting enzymes were associated with unfavorable prognosis in liver cancer. Overall, our results suggested the mRNA levels of pyrimidine metabolic rate–limiting enzymes CAD, DTYMK, RRM1, RRM2, TK1, TYMS, UCK2, NR5C2, and TK2 were predictive of lung cancer as well as other cancers.


2021 ◽  
Vol 8 ◽  
Author(s):  
Congjun Zhang ◽  
Jun Ding ◽  
Xiao Xu ◽  
Yangyang Liu ◽  
Wei Huang ◽  
...  

Background: Pancreatic cancer (PC) is one of the most lethal types of cancer with extremely poor diagnosis and prognosis, and the tumor microenvironment plays a pivotal role during PC progression. Poor prognosis is closely associated with the unsatisfactory results of currently available treatments, which are largely due to the unique pancreatic tumor microenvironment (TME).Methods: In this study, a total of 177 patients with PC from The Cancer Genome Atlas (TCGA) cohort and 65 patients with PC from the GSE62452 cohort in Gene Expression Omnibus (GEO) were included. Based on the proportions of 22 types of infiltrated immune cell subpopulations calculated by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), the TME was classified by K-means clustering and differentially expressed genes (DEGs) were determined. A combination of the elbow method and the gap statistic was used to explore the likely number of distinct clusters in the data. The ConsensusClusterPlus package was utilized to identify radiomics clusters, and the samples were divided into two subtypes.Result: Survival analysis showed that the patients with TMEscore-high phenotype had better prognosis. In addition, the TMEscore-high had better inhibitory effect on the immune checkpoint. A total of 10 miRNAs, 311 DEGs, and 68 methylation sites related to survival were obtained, which could be biomarkers to evaluate the prognosis of patients with pancreatic cancer.Conclusions: Therefore, a comprehensive description of TME characteristics of pancreatic cancer can help explain the response of pancreatic cancer to immunotherapy and provide a new strategy for cancer treatment.


Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4110
Author(s):  
Satoru Yonekura ◽  
Kosuke Ueda

Background: To assess the prognostic role and the antitumor immunological relevance of ecotropic viral integration site 2B (EVI2B) in metastatic melanoma. Methods: In this study, we integrated clinical data, mRNA expression data, and the distribution and fraction of tumor infiltrating lymphocytes (TILs) using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets (GSE65904 and GSE19234). Results: The univariate and multivariate analyses showed that higher gene expression of EVI2B was significantly associated with longer prognoses. The EVI2B-high melanoma tissue had favorable histological parameters such as a brisk global distribution pattern and clustering structure of TILs (i.e., Banfield and Raftery index) with enriched CD8+ T cells over regulatory T cells and increased cytotoxicity scores. In addition, EVI2B expression positively correlated with IFN-γ signature genes (CXCL10, CXCL9, HLA-DRA, IDO1, IFNG, and STAT1) and other various immunomodulatory genes. Conclusion: EVI2B is a novel prognostic biomarker with IFN-γ associated immune infiltration in metastatic melanoma.


2018 ◽  
Vol 485 ◽  
pp. 14-20 ◽  
Author(s):  
Xue-liang Zuo ◽  
Juan Cai ◽  
Zhi-qiang Chen ◽  
Yao Zhang ◽  
Lin-hu Liang ◽  
...  

Author(s):  
Qian Xu ◽  
Yurong Chen

Aging is an inevitable time-dependent process associated with a gradual decline in many physiological functions. Importantly, some studies have supported that aging may be involved in the development of lung adenocarcinoma (LUAD). However, no studies have described an aging-related gene (ARG)-based prognosis signature for LUAD. Accordingly, in this study, we analyzed ARG expression data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). After LASSO and Cox regression analyses, a six ARG-based signature (APOC3, EPOR, H2AFX, MXD1, PLCG2, and YWHAZ) was constructed using TCGA dataset that significantly stratified cases into high- and low-risk groups in terms of overall survival (OS). Cox regression analysis indicated that the ARG signature was an independent prognostic factor in LUAD. A nomogram based on the ARG signature and clinicopathological factors was developed in TCGA cohort and validated in the GEO dataset. Moreover, to visualize the prediction results, we established a web-based calculator yurong.shinyapps.io/ARGs_LUAD/. Calibration plots showed good consistency between the prediction of the nomogram and actual observations. Receiver operating characteristic curve and decision curve analyses indicated that the ARG nomogram had better OS prediction and clinical net benefit than the staging system. Taken together, these results established a genetic signature for LUAD based on ARGs, which may promote individualized treatment and provide promising novel molecular markers for immunotherapy.


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