scholarly journals Comprehensive Immunohistochemical Study of the SWI/SNF Complex Expression Status in Gastric Cancer Reveals an Adverse Prognosis of SWI/SNF Deficiency in Genomically Stable Gastric Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3894
Author(s):  
Marie-Isabelle Glückstein ◽  
Sebastian Dintner ◽  
Tim Tobias Arndt ◽  
Dmytro Vlasenko ◽  
Gerhard Schenkirsch ◽  
...  
Keyword(s):  
Gastroesophageal Junction ◽  
Therapy Resistance ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Aberrant Expression ◽  
Routine Diagnostics ◽  
Negative Prognostic Factor ◽  
Genes Encoding ◽  
Cancer Genome Atlas

The SWI/SNF complex has important functions in the mobilization of nucleosomes and consequently influences gene expression. Numerous studies have demonstrated that mutations or deficiency of one or more subunits can have an oncogenic effect and influence the development, progression, and eventual therapy resistance of tumor diseases. Genes encoding subunits of the SWI/SNF complex are mutated in approximately 20% of all human tumors. This study aimed to investigate the frequency, association with clinicopathological characteristics, and prognosis of immunohistochemical expression of proteins of the SWI/SNF complexes, SMARCA2, SMARCA4 SMARCB1, ARID1A, ARID1B, and PBRM1 in 477 adenocarcinomas of the stomach and gastroesophageal junction. Additionally, the tumors were classified immunohistochemically in analogy to The Cancer Genome Atlas (TCGA) classification. Overall, 32% of cases demonstrated aberrant expression of the SWI/SNF complex. Complete loss of SMARCA4 was detected in three cases (0.6%) and was associated with adverse clinical characteristics. SWI/SNF aberration emerged as an independent negative prognostic factor for overall survival in genomically stable patients in analogy to TCGA. In conclusion, determination of SWI/SNF status could be suggested in routine diagnostics in genomically stable tumors to identify patients who might benefit from new therapeutic options.

scholarly journals Pan-Cancer Analysis of the Genomic Alterations and Mutations of the Matrisome

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2046 ◽  
Author(s):  
Valerio Izzi ◽  
Martin N. Davis ◽  
Alexandra Naba
Keyword(s):  
Cancer Progression ◽  
Protein Function ◽  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Cellular Functions ◽  
Genomic Alterations ◽  
Genes Encoding ◽  
Cancer Genome Atlas ◽  
Biomechanical Changes ◽  
Pan Cancer

The extracellular matrix (ECM) is a master regulator of all cellular functions and a major component of the tumor microenvironment. We previously defined the “matrisome” as the ensemble of genes encoding ECM proteins and proteins modulating ECM structure or function. While compositional and biomechanical changes in the ECM regulate cancer progression, no study has investigated the genomic alterations of matrisome genes in cancers and their consequences. Here, mining The Cancer Genome Atlas (TCGA) data, we found that copy number alterations and mutations are frequent in matrisome genes, even more so than in the rest of the genome. We also found that these alterations are predicted to significantly impact gene expression and protein function. Moreover, we identified matrisome genes whose mutational burden is an independent predictor of survival. We propose that studying genomic alterations of matrisome genes will further our understanding of the roles of this compartment in cancer progression and will lead to the development of innovative therapeutic strategies targeting the ECM.

scholarly journals Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis

2017 ◽  
Vol 43 (3) ◽  
pp. 1090-1099 ◽  
Author(s):  
Zhonghua Jiang ◽  
Tingting Yu ◽  
Zhining Fan ◽  
Hongmei Yang ◽  
Xin Lin
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Strong Negative Correlation ◽  
Functional Studies ◽  
Expression Of Genes ◽  
Cancer Genome Atlas

Background/Aims: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. Methods: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. Results: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. Conclusion: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

scholarly journals Identification of RASSF1A Promoter Hypermethylation as a Biomarker for Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Gang Xu ◽  
Xiaoxiang Zhou ◽  
Jiali Xing ◽  
Yao Xiao ◽  
Bao Jin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Promoter Methylation ◽  
Meta Analysis ◽  
Promoter Hypermethylation ◽  
Analysis Data ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Large Tumor ◽  
Kaplan Meier ◽  
Cancer Genome Atlas

Abstract Background: RAS association domain family protein 1A (RASSF1A) promoter hypermethylation is suggested to be linked to hepatocellular carcinoma (HCC), but the results remained controversial.Methods: We evaluated how RASSF1A promoter hypermethylation affects HCC risk and its clinicopathological characteristics through meta-analysis. Data on DNA methylation in HCC and relevant clinical data were also collected based on The Cancer Genome Atlas (TCGA) database to investigate the prognostic role of RASSF1A promoter hypermethylation in HCC.Results: Forty-four articles involving 4,777 individuals were enrolled in the pooled analyses. The RASSF1A promoter methylation rate was notably higher in the HCC cases than the non-tumor cases and healthy individuals, and was significantly related to hepatitis B virus (HBV) infection-positivity and large tumor size. Kaplan–Meier survival analysis revealed that HCC cases with RASSF1A promoter hypermethylation had worse outcomes. Receiver operating characteristic curves confirmed that RASSF1A promoter methylation may be a marker of HCC-related prognoses.Conclusions: RASSF1A promoter hypermethylation is a promising biomarker for the diagnosis of HCC from tissue and peripheral blood, and is an emerging therapeutic target against HCC.

scholarly journals Pervasive transcription read-through promotes aberrant expression of oncogenes and RNA chimeras in renal carcinoma

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ana R Grosso ◽  
Ana P Leite ◽  
Sílvia Carvalho ◽  
Mafalda R Matos ◽  
Filipa B Martins ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Transcriptional Profiling ◽  
The Cancer Genome Atlas ◽  
Cancer Genes ◽  
Cell Renal Cell Carcinoma ◽  
Aberrant Expression ◽  
Chimeric Transcripts ◽  
Cancer Genome Atlas ◽  
Pervasive Transcription ◽  
Transcriptome Diversity

Aberrant expression of cancer genes and non-canonical RNA species is a hallmark of cancer. However, the mechanisms driving such atypical gene expression programs are incompletely understood. Here, our transcriptional profiling of a cohort of 50 primary clear cell renal cell carcinoma (ccRCC) samples from The Cancer Genome Atlas (TCGA) reveals that transcription read-through beyond the termination site is a source of transcriptome diversity in cancer cells. Amongst the genes most frequently mutated in ccRCC, we identified SETD2 inactivation as a potent enhancer of transcription read-through. We further show that invasion of neighbouring genes and generation of RNA chimeras are functional outcomes of transcription read-through. We identified the BCL2 oncogene as one of such invaded genes and detected a novel chimera, the CTSC-RAB38, in 20% of ccRCC samples. Collectively, our data highlight a novel link between transcription read-through and aberrant expression of oncogenes and chimeric transcripts that is prevalent in cancer.

scholarly journals miR-149-5p inhibits cell growth by regulating TWEAK/Fn14/PI3K/AKT pathway and predicts favorable survival in human osteosarcoma

2018 ◽  
Vol 32 ◽  
pp. 205873841878665 ◽  
Author(s):  
Rui-Da Xu ◽  
Fan Feng ◽  
Xiao-Sheng Yu ◽  
Zu-De Liu ◽  
Li-Feng Lao
Keyword(s):  
Cell Growth ◽  
Molecular Mechanisms ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Osteosarcoma Cell ◽  
Sequencing Data ◽  
Serine Threonine Kinase ◽  
Tnf Superfamily ◽  
Cancer Genome Atlas ◽  
Tumor Growth And Metastasis

MicroRNAs (miRNAs) as small non-coding RNAs act as either tumor suppressors or oncogenes in human cancers, of which miR-149-5p (miR-149) is involved in tumor growth and metastasis, but its role and molecular mechanisms underlying osteosarcoma growth are poorly understood. The correlation of miR-149 expression with clinicopathological characteristics and prognosis in patients with sarcoma was analyzed by The Cancer Genome Atlas (TCGA) RNA-sequencing data. Osteosarcoma cell growth affected by miR-149 was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. As a result, we found that the expression level of miR-149 was markedly downregulated in human sarcoma samples and were negatively associated with tumor size, acting as an independent prognostic factor for overall survival of the sarcoma patients. Restoration of miR-149 expression suppressed osteosarcoma cell growth, while its knockdown reversed these effects. Furthermore, we identified TNFRSF12A (TNF receptor superfamily member 12A), also called fibroblast growth factor–inducible 14 (Fn14) as a direct target of miR-149, and TNFRSF12A and its ligand TNFSF12 (TNF superfamily member 12), also called tumor necrosis factor–related weak inducer of apoptosis (TWEAK), were both negatively correlated with miR-149 expression in sarcoma samples. Knockdown of TNFRSF12A suppressed cell growth, but its overexpression weakened the antiproliferative effects of miR-149 via the PI3K/AKT (AKT serine/threonine kinase) signaling pathway. Altogether, our findings show that miR-149 functions as a tumor suppressor in osteosarcoma via inhibition of the TWEAK–Fn14 axis and represents a potential therapeutic target in patients with osteosarcoma.

scholarly journals Systematic analysis of aberrances of ferroptosis reveals its potential functional roles in cancer

2019 ◽  
Author(s):  
Zekun Liu ◽  
Qi Zhao ◽  
Zhi-Xiang Zuo ◽  
Shu-Qiang Yuan ◽  
Kai Yu ◽  
...  
Keyword(s):  
The Cancer Genome Atlas ◽  
Copy Number Alterations ◽  
Aberrant Expression ◽  
Systematic Analysis ◽  
Functional Roles ◽  
Normal Tissues ◽  
Potential Index ◽  
Cancer Genome Atlas ◽  
Regulator Genes ◽  
Worse Prognosis

SummaryFerroptosis is a type of cell death that related to cancer, however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, copy number alterations (CNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers, and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolism pathways but positively associated with several important metastasis-related pathways and immune-related pathways. Higher FPI predicted worse prognosis in several tumors, while FPI and FRGs impacted drug sensitivity. Our study presents a systematical analysis of ferroptosis and its regulatory genes, and highlights the potential of ferroptosis-based cancer therapy.

scholarly journals Germline genetic determination of cancer progression and survival

2019 ◽  
Author(s):  
Benjamin N. Ostendorf ◽  
Kimia N. Tafreshian ◽  
Nneoma Adaku ◽  
Jana Bilanovic ◽  
Bernardo Tavora ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cell ◽  
Human Melanoma ◽  
The Cancer Genome Atlas ◽  
Genetic Determination ◽  
Apoe Protein ◽  
Cancer Genome Atlas ◽  
Protein Variants ◽  
Surprising Finding

We report the surprising finding that common germline polymorphisms of APOE, present in approximately 39% of Caucasians, predict survival outcomes in human melanoma. Analysis of The Cancer Genome Atlas revealed that carriers of the APOE2 variant experienced shorter survival relative to APOE3 homozygotes, while APOE4 variant carriers exhibited increased survival. Consistent with this, melanoma growth in human APOE knock-in mice followed the order of APOE2 > APOE3 > APOE4, revealing causal regulation of progression by APOE variants. Mechanistically, recombinant ApoE protein variants differentially suppressed melanoma cell invasion and endothelial recruitment phenotypes. Moreover, tumors in APOE4 mice exhibited greater immune cell infiltration and activation relative to tumors of APOE2 mice. These findings support the notion that human germline genetic makeup can impact the trajectory of a future malignancy.

scholarly journals A novel prognostic signature of immune-related lncRNA pairs in lung adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Liu ◽  
Qiuhong Wu ◽  
Xuejiao Fan ◽  
Wen Li ◽  
Xiaogang Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Risk Model ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Clinicopathological Characteristics ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Specific Expression ◽  
Expression Levels ◽  
Cancer Genome Atlas

AbstractLung adenocarcinoma (LUAD) is the most common subtype of lung cancer, but the prognosis of LUAD patients remains unsatisfactory. Here, we retrieved the RNA-seq data of LUAD cohort from The Cancer Genome Atlas (TCGA) database and then identified differentially expressed immune-related lncRNAs (DEirlncRNAs) between LUAD and normal controls. Based on a new method of cyclically single pairing along with a 0-or-1 matrix, we constructed a novel prognostic signature of 8 DEirlncRNA pairs in LUAD with no dependence upon specific expression levels of lncRNAs. This prognostic model exhibited significant power in distinguishing good or poor prognosis of LUAD patients and the values of the area under the curve (AUC) were all over 0.70 in 1, 3, 5 years receiver operating characteristic (ROC) curves. Moreover, the risk score of the model could serve as an independent prognostic factor for patients with LUAD. In addition, the risk model was significantly associated with clinicopathological characteristics, tumor-infiltrating immune cells, immune-related molecules and sensitivity of anti-tumor drugs. This novel signature of DEirlncRNA pairs in LUAD, which did not require specific expression levels of lncRNAs, might be used to guide the administration of patients with LUAD in clinical practice.

scholarly journals A novel similarity score based on gene ranks to reveal genetic relationships among diseases

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10576
Author(s):  
Dongmei Luo ◽  
Chengdong Zhang ◽  
Liwan Fu ◽  
Yuening Zhang ◽  
Yue-Qing Hu
Keyword(s):  
Genetic Relationships ◽  
Similarity Measures ◽  
Similarity Score ◽  
The Cancer Genome Atlas ◽  
Genetic Mechanisms ◽  
Cancer Genome Atlas ◽  
Cancer Types ◽  
Pan Cancer ◽  
Cancer Studies

Knowledge of similarities among diseases can contribute to uncovering common genetic mechanisms. Based on ranked gene lists, a couple of similarity measures were proposed in the literature. Notice that they may suffer from the determination of cutoff or heavy computational load, we propose a novel similarity score SimSIP among diseases based on gene ranks. Simulation studies under various scenarios demonstrate that SimSIP has better performance than existing rank-based similarity measures. Application of SimSIP in gene expression data of 18 cancer types from The Cancer Genome Atlas shows that SimSIP is superior in clarifying the genetic relationships among diseases and demonstrates the tendency to cluster the histologically or anatomically related cancers together, which is analogous to the pan-cancer studies. Moreover, SimSIP with simpler form and faster computation is more robust for higher levels of noise than existing methods and provides a basis for future studies on genetic relationships among diseases. In addition, a measure MAG is developed to gauge the magnitude of association of anindividual gene with diseases. By using MAG the genes and biological processes significantly associated with colorectal cancer are detected.

scholarly journals Identification and Validation of Two Novel Prognostic lncRNAs in Kidney Renal Clear Cell Carcinoma

2018 ◽  
Vol 48 (6) ◽  
pp. 2549-2562 ◽  
Author(s):  
Jukun Song ◽  
Juxiang Peng ◽  
Chen Zhu ◽  
Guohui Bai ◽  
Yongda Liu ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Molecular Biomarkers ◽  
The Cancer Genome Atlas ◽  
Aberrant Expression ◽  
Cerna Network ◽  
Poor Treatment ◽  
Cancer Genome Atlas

Background/Aims: Kidney renal clear cell carcinoma (KIRC) is one of the most fatal malignancies due to late diagnosis and poor treatment. To improve its prognosis, a screening for molecular biomarkers of KIRC is urgently needed. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and prognosis of cancers. However, it is not clear whether lncRNAs can be used as molecular biomarkers in predicting the survival of KIRC patients. Methods: In this study, our aim was to identify lncRNAs/mRNAs signatures and their prognostic values in KIRC. The aberrant expression profile of mRNAs and lncRNAs in 529 KIRC tissues and 72 adjacent non-tumor pancreatic tissues were obtained from the Cancer Genome Atlas (TCGA). A weighted gene co-expression network analysis (WGCNA) of two key lncRNAs was constructed. We constructed an aberrant lncRNA-mRNA-miRNA ceRNA network in CESC. In addition, Gene Ontology (GO) and KEGG pathway analysis were performed. Results: Using lncRNA/mRNA expression profiling data, the overall analysis revealed that two novel lncRNA signatures (DNM1P35 and MIR155HG) and several mRNAs were found to be significantly correlated with KIRC patient’s overall analysis. Based on the target gene of the two lncRNA in co-expression network, the GO and KEGG analysis were also performed. A dysregulated lncRNA-related ceRNA network was also observed. Conclusion: These results suggested that the two novel lncRNAs signatures may act as independent prognostic biomarkers for predicting the survival of KIRC patient.

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