scholarly journals Characterization of Leading Dysregulated Plasma-Proteome Associated Genes in Patients with Gastro-Esophageal Cancers.

Author(s):  
Frederick Vizeacoumar ◽  
Lynn Dwernychuk ◽  
Adnan Zaidi ◽  
Andrew Freywald ◽  
Franco Vizeacoumar ◽  
...  

Abstract Background: Gastro-esophageal cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of gastro-esophageal cancers to identify new therapeutic targets and to yield predictive response to the available therapies. Our study aims to identify leading genes that are dysregulated (upregulated or downregulated) in patients with gastro-esophageal cancers.Methods: We examined gene expression data for those genes whose protein products can be detected in the plasma in 600 independent tumor samples and 46 matching normal tissue samples using the Cancer Genome Atlas (TCGA) to identify leading genes that are dysregulated in patients with gastro-esophageal cancers. Non-parametric Mann-Whitney-U test was used to evaluate differential expression of genes using a cut-off of P< 0.05.Results: The comparison between tumors sample and healthy tissue showed BIRC5 (p=2.61 E-08), APOC2 (p=3.23E-08), CENPF (p=4.38E-08), STMN1 (p=5.74E-08), and HNRPC (p=8.21E-08) were the leading genes significantly overexpressed in esophageal cancer whereas CST1 (p=3.97 E-21), INHBA (p=9.22E-20), ACAN (p=1.08E-19), HSP90AB1 (p=2.62E-19), and HSPD1 (p=3.91E-19) were the leading genes that were overexpressed in stomach cancer. Conversely, C16orf89 (9.78E-08), AR (1.01E-07), CKB (1.17E-07), ADH1B (1.79E-07), and NCAM1 (2.15E-07) were the leading gene that were significantly downregulated in esophageal cancer whereas GPX3 (1.65E-19), CLEC3B (5.70E-19), CFD (5.68E-18), GSN (4.5IE-17), and CCL14 (1.12E-16) were significantly downregulated in stomach cancer. Furthermore, Stage-based examination showed stage-specific differential expression of various genes as well as stage-wise increasing or decreasing up-regulation or down-regulation of selected genes, respectively. Conclusions: The present study identified leading upregulated and downregulated genes in gastro-esophageal cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted-treatment.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Frederick S. Vizeacoumar ◽  
Hongyu Guo ◽  
Lynn Dwernychuk ◽  
Adnan Zaidi ◽  
Andrew Freywald ◽  
...  

AbstractGastro-esophageal (GE) cancers are one of the major causes of cancer-related death in the world. There is a need for novel biomarkers in the management of GE cancers, to yield predictive response to the available therapies. Our study aims to identify leading genes that are differentially regulated in patients with these cancers. We explored the expression data for those genes whose protein products can be detected in the plasma using the Cancer Genome Atlas to identify leading genes that are differentially regulated in patients with GE cancers. Our work predicted several candidates as potential biomarkers for distinct stages of GE cancers, including previously identified CST1, INHBA, STMN1, whose expression correlated with cancer recurrence, or resistance to adjuvant therapies or surgery. To define the predictive accuracy of these genes as possible biomarkers, we constructed a co-expression network and performed complex network analysis to measure the importance of the genes in terms of a ratio of closeness centrality (RCC). Furthermore, to measure the significance of these differentially regulated genes, we constructed an SVM classifier using machine learning approach and verified these genes by using receiver operator characteristic (ROC) curve as an evaluation metric. The area under the curve measure was > 0.9 for both the overexpressed and downregulated genes suggesting the potential use and reliability of these candidates as biomarkers. In summary, we identified leading differentially expressed genes in GE cancers that can be detected in the plasma proteome. These genes have potential to become diagnostic and therapeutic biomarkers for early detection of cancer, recurrence following surgery and for development of targeted treatment.


1927 ◽  
Vol 23 (8) ◽  
pp. 847-847
Author(s):  
A. Кlеіn

Almost half of all esophageal cancers, according to A. Klein's data show that the bifurcation area is responsible for almost half of all esophageal cancers. The disease predominates in men and ranks second in the overall cancer statistics after stomach cancer, occurring most often in the sixth decade.


2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Delong Zhang ◽  
Huanggui Zhou ◽  
Jun Liu ◽  
Jie Mao

Glioma is a lethal, malignant intracranial tumor that becomes progressively common. It has been shown that long noncoding RNAs (lncRNAs) serve important roles in numerous diseases such as gliomas. lncRNAs can regulate the expression of targeted genes through various mechanisms. To identify a novel lncRNA that may be critical in glioma, the present study downloaded the RNA expression profiles of 171 glioma tissues and 5 normal tissues from The Cancer Genome Atlas (TCGA) database using the TCGAbiolinks package in R. Then, lncRNAs in the downloaded TCGA data were identified using the HUGO Gene Nomenclature Committee (HGNC). Based on the fragments per kilobase million value, differential expression analysis was conducted using the limma package in R. In addition, receiver operating characteristic (ROC) analysis was performed, and the area under the curve (AUC) was evaluated using the ROCR package in R. A total of 178 lncRNAs corresponding to differentially expressed genes with an AUC >0.85 were selected. Upon identifying the differential lncRNAs, ceRNA networks were constructed with these differential lncRNAs using the starbase database. From these networks, the top 10% hub genes were selected. In addition, the present study randomly selected 4 lncRNAs for quantitative polymerase chain reaction validation in tissue samples. The results revealed that lncRNA ASB16-AS1 exhibited significantly differential expression in tissue samples and was significantly associated with tumor staging and grading. Furthermore, the proliferation, invasion, and migration of U87MG and U251 glioblastoma stem-like cells (U87GS, U251GS) were significantly inhibited upon inhibition of ASB16-AS1, and the expression of key proteins in the EMT signaling pathway was affected by knocking down ASB16-AS1. Overall, the present study revealed that lncRNA ASB16-AS1 improves the proliferation, migration, and invasion of glioma cells.


2021 ◽  
Vol 49 (1) ◽  
pp. 030006052098154
Author(s):  
Xin Yuan ◽  
Yize Zhang ◽  
Zujiang Yu

Objective To investigate the association between microRNA-3615 (miR-3615) expression and the prognosis and clinicopathological features in patients with hepatocellular carcinoma (HCC). Methods We obtained clinicopathological and genomic data and prognostic information on HCC patients from The Cancer Genome Atlas (TCGA) database. We then analyzed differences in miR-3615 expression levels between HCC and adjacent tissues using SPSS software, and examined the relationships between miR-3615 expression levels and clinicopathological characteristics. We also explored the influence of miR-3615 expression levels on the prognosis of HCC patients using Kaplan–Meier survival curve analysis. Results Based on data for 345 HCC and 50 adjacent normal tissue samples, expression levels of miR-3615 were significantly higher in HCC tissues compared with adjacent tissues. MiR-3615 expression levels in HCC patients were negatively correlated with overall survival time and positively correlated with high TNM stage, serum Ki-67 expression level, and serum alpha-fetoprotein level. There were no significant correlations between miR-3615 expression and age, sex, and pathological grade. Conclusion MiR-3615 may be a promising new biomarker and prognostic factor for HCC.


2021 ◽  
Vol 28 ◽  
pp. 107327482098851
Author(s):  
Zeng-Hong Wu ◽  
Yun Tang ◽  
Yan Zhou

Background: Epigenetic changes are tightly linked to tumorigenesis development and malignant transformation’ However, DNA methylation occurs earlier and is constant during tumorigenesis. It plays an important role in controlling gene expression in cancer cells. Methods: In this study, we determining the prognostic value of molecular subtypes based on DNA methylation status in breast cancer samples obtained from The Cancer Genome Atlas database (TCGA). Results: Seven clusters and 204 corresponding promoter genes were identified based on consensus clustering using 166 CpG sites that significantly influenced survival outcomes. The overall survival (OS) analysis showed a significant prognostic difference among the 7 groups (p<0.05). Finally, a prognostic model was used to estimate the results of patients on the testing set based on the classification findings of a training dataset DNA methylation subgroups. Conclusions: The model was found to be important in the identification of novel biomarkers and could be of help to patients with different breast cancer subtypes when predicting prognosis, clinical diagnosis and management.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Yan ◽  
Zuotian Huang ◽  
Tong Mou ◽  
Yunhai Luo ◽  
Yanyao Liu ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors, with a high rate of recurrence worldwide. This study aimed to investigate the mechanism underlying the progression of HCC and to identify recurrence-related biomarkers. Methods We first analyzed 132 HCC patients with paired tumor and adjacent normal tissue samples from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). The expression profiles and clinical information of 372 HCC patients from The Cancer Genome Atlas (TCGA) database were next analyzed to further validate the DEGs, construct competing endogenous RNA (ceRNA) networks and discover the prognostic genes associated with recurrence. Finally, several recurrence-related genes were evaluated in two external cohorts, consisting of fifty-two and forty-nine HCC patients, respectively. Results With the comprehensive strategies of data mining, two potential interactive ceRNA networks were constructed based on the competitive relationships of the ceRNA hypothesis. The ‘upregulated’ ceRNA network consists of 6 upregulated lncRNAs, 3 downregulated miRNAs and 5 upregulated mRNAs, and the ‘downregulated’ network includes 4 downregulated lncRNAs, 12 upregulated miRNAs and 67 downregulated mRNAs. Survival analysis of the genes in the ceRNA networks demonstrated that 20 mRNAs were significantly associated with recurrence-free survival (RFS). Based on the prognostic mRNAs, a four-gene signature (ADH4, DNASE1L3, HGFAC and MELK) was established with the least absolute shrinkage and selection operator (LASSO) algorithm to predict the RFS of HCC patients, the performance of which was evaluated by receiver operating characteristic curves. The signature was also validated in two external cohort and displayed effective discrimination and prediction for the RFS of HCC patients. Conclusions In conclusion, the present study elucidated the underlying mechanisms of tumorigenesis and progression, provided two visualized ceRNA networks and successfully identified several potential biomarkers for HCC recurrence prediction and targeted therapies.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 489
Author(s):  
Sylwia Prochowska ◽  
Agnieszka Partyka ◽  
Wojciech Niżański

Apoptosis is a crucial process in spermatogenesis, responsible for the elimination of abnormal sperm cells and testicular regression out of breeding season. The aim of this study was to assess if the expression of apoptosis-related genes in testicular tissue of domestic cats differed: (1) between normozoospermic and teratozoospermic donors, and (2) between reproductive and non-reproductive season. The expression of genes: BCL2L1, BCL2, BAX, BAD, FAS, FASLG, and caspases (CASP3, CASP8, CASP9, and CASP10) was analyzed by qRT-PCR in testicular tissue samples. During non-reproductive season significantly higher expression of two anti-apoptotic genes (BCL2L1 and BCL2) was observed. Additionally, there was a significant higher expression of CASP10 in teratozoospermic cats during non-reproductive than during reproductive season. No differences were noted between normozoospermic and teratozoospermic groups. Upregulation of some genes during the non-reproductive season indicates engagement of apoptotic mechanisms in the seasonal changes of semen quality in cats, however further studies on protein levels and analysis of changes on distinct testicular germinal layers are required. At the same time, teratozoospermia in the general population of cats seems to be not connected with dysregulation of apoptosis in the testes.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 257
Author(s):  
Yan Gu ◽  
Mathilda Jing Chow ◽  
Anil Kapoor ◽  
Xiaozeng Lin ◽  
Wenjuan Mei ◽  
...  

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Meiwei Mu ◽  
Yi Tang ◽  
Zheng Yang ◽  
Yuling Qiu ◽  
Xiaohong Li ◽  
...  

Objective. To explore the expression of immune-related lncRNAs in colon adenocarcinoma and find out the effect on how these lncRNAs influence the development and prognosis of colon adenocarcinoma. Method. Transcriptome data of colon adenocarcinoma from The Cancer Genome Atlas (TCGA) were downloaded, and gene sets “IMMUNE RESPONSE” and “IMMUNE SYSTEM PROCESS” were sought from the Molecular Signatures Database (MSigDB). The expression of immune-related genes was extracted that were immune-related mRNAs. Then, the immune-related lncRNAs were sought out by utilizing of the above data. Clinical traits were combined with immune-related lncRNAs, so that prognostic-related lncRNAs were identified by Cox regression. Multivariate Cox regression was built to calculate risk scores. Relationships between clinical traits and immune-related lncRNAs were also calculated. Result. A total of 480 colorectal adenocarcinoma patients and 41 normal control patients’ transcriptome sequencing data of tissue samples were obtained from TCGA database. 918 immune-related lncRNAs were screened. Cox regression showed that 34 immune-related lncRNAs were associated with colon adenocarcinoma prognosis. Seven lncRNAs were independent risk factors. Conclusion. This study revealed that some lncRNAs can affect the development and prognosis of colon adenocarcinoma. It may provide new theory evidence of molecular mechanism for the future research and molecular targeted therapy of colon adenocarcinoma.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Carmen P. Wong ◽  
Urszula T. Iwaniec ◽  
Russell T. Turner

AbstractSixteen-week-old female C57BL/6J mice were sacrificed aboard the International Space Station after 37 days of flight (RR-1 mission) and frozen carcasses returned to Earth. RNA was isolated from interscapular brown adipose tissue (BAT) and gonadal white adipose tissue (WAT). Spaceflight resulted in differential expression of genes in BAT consistent with increased non-shivering thermogenesis and differential expression of genes in WAT consistent with increased glucose uptake and metabolism, adipogenesis, and β-oxidation.


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