LncRNA DLGAP1-AS2 Overexpression Associates with Gastric Tumorigenesis; A Promising Diagnostic and Therapeutic Target

Abstract Background: Aberrant expression of long noncoding RNAs (lncRNAs) is associated with the progression of human cancers, including gastric cancer (GC). The function of lncRNA DLGAP1-AS2, as an oncogene, has been identified in glioma, hepatocellular carcinoma, and cholangiocarcinoma but not in other malignancies. Therefore, this study was aimed to explore the association of DLGAP1-AS2 with gastric tumorigenesis and beyond.Methods and Results: The expression level of DLGAP1-AS2 was prevaluated in GC datasets from Gene Expression Omnibus (GEO). Moreover, qRT-PCR experiment was performed on 25 paired GC and adjacent normal tissue samples. The Cancer Genome Atlas (TCGA) data were also analyzed for further validations. Consistent with data obtained from GEO datasets, qRT-PCR results revealed that DLGAP1-AS2 was significantly (p < 0.0032) upregulated in GC specimens compared to normal samples, which was additionally confirmed using TCGA analysis (p<0.0001). DLGAP1-AS2 expression level was also correlated with age (p =0.0008), lymphatic and vascular invasion (p =0.0415) in internal samples. Also, a significant correlation was found between DLGAP1-AS2 and YAP1 expression, as its valid downstream target, in GC samples. Besides, analysis of other prevalent tumor entities using TCGA illustrated the significant overexpression of DLGAP1-AS2 in lung, colorectal, and prostate cancers, further indicating its promise as an oncogene. Moreover, ROC curve analysis showed the high accuracy of the DLGAP1-AS2 expression pattern as a diagnostic biomarker for gastric and colorectal cancers. Conclusion: Our findings indicated that DLGAP1-AS2 might display oncogenic property in gastric tumorigenesis and be suggested as a therapeutic and diagnostic target.

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Upregulated Seizure-Related 6 Homolog-Like 2 Is a Prognostic Predictor of Hepatocellular Carcinoma

Disease Markers ◽

10.1155/2020/7318703 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Linhe Wang ◽

Xiangchao Ling ◽

Caihui Zhu ◽

Zhiheng Zhang ◽

Ziming Wang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cancer Progression ◽

Disease Free Survival ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Poor Overall Survival ◽

Tissue Samples ◽

Prognostic Predictor ◽

Qrt Pcr ◽

Cancer Genome Atlas

Seizure-related 6 homolog-like 2 (SEZ6L2), which is localized on the cell surface, has been found to be associated with tumor angiogenesis and lung cancer progression. However, the role of SEZ6L2 in hepatocellular carcinoma (HCC) is still unclear. We obtained data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate SEZ6L2 expression and regulation in HCC. Then, HCC tissue samples were collected to verify SEZ6L2 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining (IHC). Patient information was collected for survival and prognosis analysis. qRT-PCR, IHC, and bioinformatics analysis showed that the SEZ6L2 protein was highly expressed in HCC samples. Clinical data showed that high SEZ6L2 protein expression was correlated with tumor-node-metastasis (TNM) stages (P=0.046), tumor number (P=0.016), and tumor size (P=0.029). Meanwhile, SEZ6L2 overexpression was closely associated with poor overall survival and disease-free survival in HCC patients. Moreover, SEZ6L2 is an independent prognostic predictor for the survival of HCC patients. This study suggests a significant correlation between SEZ6L2 and HCC, which means that SEZ6L2 may potentially serve as a useful prognostic biomarker for HCC patients.

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Downstream Neighbor of SON (DONSON) Expression Is Enhanced in Phenotypically Aggressive Prostate Cancers

Cancers ◽

10.3390/cancers12113439 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3439 ◽

Cited By ~ 1

Author(s):

Niklas Klümper ◽

Marthe von Danwitz ◽

Johannes Stein ◽

Doris Schmidt ◽

Anja Schmidt ◽

...

Keyword(s):

Cell Cycle Progression ◽

Locally Advanced ◽

Metastatic Potential ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Cancer Genome Atlas ◽

Prostate Cancers ◽

Migration Capacity

Downstream neighbor of Son (DONSON) plays a crucial role in cell cycle progression and in maintaining genomic stability, but its role in prostate cancer (PCa) development and progression is still underinvestigated. Methods: DONSON mRNA expression was analyzed with regard to clinical-pathological parameters and progression using The Cancer Genome Atlas (TCGA) and two publicly available Gene Expression Omnibus (GEO) datasets of PCa. Afterwards, DONSON protein expression was assessed via immunohistochemistry on a comprehensive tissue microarray (TMA). Subsequently, the influence of a DONSON-knockdown induced by the transfection of antisense-oligonucleotides on proliferative capacity and metastatic potential was investigated. DONSON was associated with an aggressive phenotype in the PCa TCGA cohort, two GEO PCa cohorts, and our PCa TMA cohort as DONSON expression was particularly strong in locally advanced, metastasized, and dedifferentiated carcinomas. Thus, DONSON expression was notably upregulated in distant and androgen-deprivation resistant metastases. In vitro, specific DONSON-knockdown significantly reduced the migration capacity in the PCa cell lines PC-3 and LNCaP, which further suggests a tumor-promoting role of DONSON in PCa. In conclusion, the results of our comprehensive expression analyses, as well as the functional data obtained after DONSON-depletion, lead us to the conclusion that DONSON is a promising prognostic biomarker with oncogenic properties in PCa.

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Overexpression of B7-H3 Is Associated With Poor Prognosis in Laryngeal Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.759528 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yixuan Li ◽

Qian Cai ◽

Ximing Shen ◽

Xiaoting Chen ◽

Zhong Guan

Keyword(s):

Gene Expression ◽

Laryngeal Cancer ◽

Poor Prognosis ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Normal Tissues ◽

Qrt Pcr ◽

Node Metastasis ◽

B7 Family

The immune checkpoint molecule, B7-H3, which belongs to the B7 family, has been shown to be overexpressed in various cancers. Its role in tumors is not well defined, and many studies suggest that it is associated with poor clinical outcomes. The effect of B7-H3 on laryngeal cancer has not been reported. This study investigated the expression of B7-H3 in laryngeal squamous cell carcinoma (LSCC), and its relationship with clinicopathological factors and prognosis of LSCC patients. The gene expression quantification data and clinical data of LSCC retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database were analyzed to determine the diagnostic and prognostic roles of B7-H3. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed to determine the gene expression level of B7-H3 between LSCC tissues and paired normal adjacent tissues. In addition, TCGA RNA-seq data was analyzed to evaluate the expression level of B7 family genes. Next, the protein expression of B7-H3 and CD8 in LSCC was determined using immunohistochemistry and immunofluorescence. qRT-PCR results showed that the expression level of B7-H3 mRNA was significantly higher in LSCC tissues than in adjacent normal tissues. Similar results were obtained from the TCGA analysis. The expression of B7-H3 was significantly associated with T stage, lymph node metastasis, and pathological tumor node metastasis (TNM) stage, and it was also an independent factor influencing the overall survival time (OS) of patients with LSCC. In addition, B7-H3 was negatively correlated with CD8+T cells. These results show that B7-H3 is upregulated in LSCC. Therefore, B7-H3 may serve as a biomarker of poor prognosis and a promising therapeutic target in LSCC.

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Comprehensive analyses of competing endogenous RNA networks reveal potential biomarkers for predicting hepatocellular carcinoma recurrence

BMC Cancer ◽

10.1186/s12885-021-08173-0 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ping Yan ◽

Zuotian Huang ◽

Tong Mou ◽

Yunhai Luo ◽

Yanyao Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Malignant Tumors ◽

Expression Profiles ◽

Clinical Information ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

High Rate ◽

Competing Endogenous Rna ◽

Tissue Samples ◽

Potential Biomarkers

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.

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Multiscale-omic assessment of EWSR1-NFATc2 fusion positive sarcomas identifies the mTOR pathway as a potential therapeutic target

npj Precision Oncology ◽

10.1038/s41698-021-00177-0 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Nathan D. Seligson ◽

Richard D. Maradiaga ◽

Colin M. Stets ◽

Howard M. Katzenstein ◽

Sherri Z. Millis ◽

...

Keyword(s):

Ewing Sarcoma ◽

Additional Data ◽

Gene Expression Omnibus ◽

Mtor Pathway ◽

The Cancer Genome Atlas ◽

Molecular Characteristics ◽

Potential Therapeutic Target ◽

Disease Stabilization ◽

Cancer Genome Atlas ◽

Ewing Family Of Tumors

AbstractSarcomas harboring EWSR1-NFATc2 fusions have historically been categorized and treated as Ewing sarcoma. Emerging evidence suggests unique molecular characteristics and chemotherapy sensitivities in EWSR1-NFATc2 fusion positive sarcomas. Comprehensive genomic profiles of 1024 EWSR1 fusion positive sarcomas, including 14 EWSR1-NFATc2 fusions, were identified in the FoundationCore® database. Additional data from the Gene Expression Omnibus, the Genomics of Drug Sensitivity in Cancer and The Cancer Genome Atlas datasets were included for analysis. EWSR1-NFATc2 fusion positive sarcomas were genomically distinct from traditional Ewing sarcoma and demonstrated upregulation of the mTOR pathway. We also present a case of a 58-year-old male patient with metastatic EWSR1-NFATc2 fusion positive sarcoma who achieved 47 months of disease stabilization when treated with combination mTOR and VEGF inhibition. EWSR1-NFATc2 fusion positive sarcomas are molecularly distinct entities with overactive mTOR signaling; which may be therapeutically targetable. These findings support the use of precision medicine in the Ewing family of tumors.

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Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target

Scientific Reports ◽

10.1038/s41598-019-54545-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Ritu Pandey ◽

Muhan Zhou ◽

Shariful Islam ◽

Baowei Chen ◽

Natalie K Barker ◽

...

Keyword(s):

Cell Adhesion ◽

Pancreatic Ductal Adenocarcinoma ◽

Therapeutic Target ◽

Cell Activity ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Ductal Adenocarcinoma ◽

Wild Type ◽

Cancer Genome Atlas ◽

Novel Therapeutic

AbstractWe investigated biomarker CEACAM6, a highly abundant cell surface adhesion receptor that modulates the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDA). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) RNA-Seq data from PDA patients were analyzed for CEACAM6 expression and evaluated for overall survival, association, enrichment and correlations. A CRISPR/Cas9 Knockout (KO) of CEACAM6 in PDA cell line for quantitative proteomics, mitochondrial bioenergetics and tumor growth in mice were conducted. We found CEACAM6 is over-expressed in primary and metastatic basal and classical PDA subtypes. Highest levels are in classical activated stroma subtype. CEACAM6 over-expression is universally a poor prognostic marker in KRAS mutant and wild type PDA. High CEACAM6 expression is associated with low cytolytic T-cell activity in both basal and classical PDA subtypes and correlates with low levels of T-REG markers. In HPAF-II cells knockout of CEACAM6 alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport and autophagy. CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity. HPAF-II CEACAM6−/− cells are growth suppressed by >65% vs. wild type in mice bearing tumors. CEACAM6, a key regulator affects several hallmarks of PDA including the fibrotic reaction, immune regulation, energy metabolism and is a novel therapeutic target in PDA.

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Effect of Different Expression of Immune-Related lncRNA on Colon Adenocarcinoma and Its Relation to Prognosis

BioMed Research International ◽

10.1155/2020/6942740 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Meiwei Mu ◽

Yi Tang ◽

Zheng Yang ◽

Yuling Qiu ◽

Xiaohong Li ◽

...

Keyword(s):

Cox Regression ◽

Colon Adenocarcinoma ◽

The Cancer Genome Atlas ◽

Risk Scores ◽

Future Research ◽

Sequencing Data ◽

Tissue Samples ◽

Gene Sets ◽

Cancer Genome Atlas ◽

Immune Related Genes

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.

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Data mining of immune-related prognostic genes in metastatic melanoma microenvironment

Bioscience Reports ◽

10.1042/bsr20201704 ◽

2020 ◽

Vol 40 (11) ◽

Author(s):

Wei Han ◽

Biao Huang ◽

Xiao-Yu Zhao ◽

Guo-Liang Shen

Keyword(s):

Gene Expression ◽

Tumor Microenvironment ◽

Metastatic Melanoma ◽

Interaction Network ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Protein Protein Interaction ◽

Subtype Identification ◽

Cancer Genome Atlas ◽

Immune Related Genes

Abstract Skin cutaneous melanoma (SKCM) is one of the most deadly malignancies. Although immunotherapies showed the potential to improve the prognosis for metastatic melanoma patients, only a small group of patients can benefit from it. Therefore, it is urgent to investigate the tumor microenvironment in melanoma as well as to identify efficient biomarkers in the diagnosis and treatments of SKCM patients. A comprehensive analysis was performed based on metastatic melanoma samples from the Cancer Genome Atlas (TCGA) database and ESTIMATE algorithm, including gene expression, immune and stromal scores, prognostic immune-related genes, infiltrating immune cells analysis and immune subtype identification. Then, the differentially expressed genes (DEGs) were obtained based on the immune and stromal scores, and a list of prognostic immune-related genes was identified. Functional analysis and the protein–protein interaction network revealed that these genes enriched in multiple immune-related biological processes. Furthermore, prognostic genes were verified in the Gene Expression Omnibus (GEO) databases and used to predict immune infiltrating cells component. Our study revealed seven immune subtypes with different risk values and identified T cells as the most abundant cells in the immune microenvironment and closely associated with prognostic outcomes. In conclusion, the present study thoroughly analyzed the tumor microenvironment and identified prognostic immune-related biomarkers for metastatic melanoma.

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Clinical Significance of miR-210 and its Prospective Signaling Pathways in Non-Small Cell Lung Cancer: Evidence from Gene Expression Omnibus and the Cancer Genome Atlas Data Mining with 2763 Samples and Validation via Real-Time Quantitative PCR

Cellular Physiology and Biochemistry ◽

10.1159/000488823 ◽

2018 ◽

Vol 46 (3) ◽

pp. 925-952 ◽

Cited By ~ 12

Author(s):

Rong-quan He ◽

Wei-luan Cen ◽

Jie-mei Cen ◽

Wei-ning Cen ◽

Jia-yi Li ◽

...

Keyword(s):

Clinical Significance ◽

Meta Analysis ◽

Gene Expression Omnibus ◽

Small Cell ◽

The Cancer Genome Atlas ◽

Small Cell Lung ◽

Free Survival ◽

Real Time Quantitative Pcr ◽

Cancer Genome Atlas ◽

Genome Atlas

Background/Aims: Since the function of microRNA (miR)-210 in non-small cell lung cancer (NSCLC) remains unclear, we aimed to explore the clinical significance of miR-210 in NSCLC. Methods: NSCLC-related data from 1673 samples on Gene Expression Omnibus and 1090 samples on The Cancer Genome Atlas were obtained and analyzed. The expression level of miR-210 was validated via real-time quantitative PCR analysis with 125 paired clinical samples. A meta-analysis was performed to generate a comprehensive understanding of miR-210 expression and its clinical significance in NSCLC. In addition, bioinformatics analysis was also conducted to reveal the potential underlying mechanism of miR-210 action in NSCLC. Results: miR-210 expression was consistently elevated in NSCLC solid tissue samples. However, its expression was controversial in easily obtained body fluids (i.e., blood, plasma, and serum). Moreover, an overall pooled meta-analysis implied a comparatively higher level of miR-210 expression in NSCLC cancerous tissue than in normal control tissue (P < 0.001). In addition, a meta-analysis of outcome revealed a significant diagnostic capacity of miR-210 in NSCLC by detecting its expression in serum and sputum (area under the summary receiver operating characteristic curve 0.82 and 0.81, respectively). miR-210 overexpression was associated with poor progression-free survival (PFS) in NSCLC and was negatively related to overall survival and disease-free survival. Bioinformatic gene enrichment and annotation analyses showed that the target genes of miR-210 were greatly enriched in cell adhesion and plasma membrane, and three pathways were considered to be the main functional circuits of miR-210: renin secretion, the cGMP-PKG signaling pathway, and cell adhesion molecules. Conclusion: In NSCLC, miR-210 expression was elevated and overexpression indicated poor PFS. Expression level of miR-210 in serum and sputum showed significant diagnostic value for NSCLC.

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Elevated expression of ASF1B correlates with poor prognosis in human lung adenocarcinoma

Personalized Medicine ◽

10.2217/pme-2020-0112 ◽

2021 ◽

Vol 18 (2) ◽

pp. 115-127

Author(s):

Zhenxing Feng ◽

Jiao Zhang ◽

Yafang Zheng ◽

Qingzhang Wang ◽

Xiaochuan Min ◽

...

Keyword(s):

Overall Survival ◽

Lung Adenocarcinoma ◽

Tumor Development ◽

Tumor Stage ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Advanced Tumor Stage ◽

Aberrant Expression ◽

Free Survival ◽

Advanced Tumor

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.

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