scholarly journals Integrated Transcriptomics Explored the Cancer-Promoting Genes CDKN3 in Esophageal Squamous Cell Cancer

2020 ◽  
Author(s):  
Wanpeng Wang ◽  
Kai Liao ◽  
HaoChun Guo ◽  
Suqin Zhou ◽  
Ran Yu ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Expression Level ◽  
Clinical Staging ◽  
P Value ◽  
Tissue Samples ◽  
Protein Coding ◽  
Seed Gene ◽  
Expression Rate

Abstract Background and objectives: The aims of the present study were to explore the critical genes that related to development of ESCC by integrated transcriptomics and investigate the clinical significance by experimental validation. Methods: The datasets of protein-coding genes expression which involved in ESCC were downloaded from GEO database. The "Robustrankaggreg" package was used for data integration, and the different expression genes (DEGs) were identified based the cut-off criteria as follows: adjust p-value < 0.05, |Log2 fold change (FC)| ≥ 1.5; The protein expression of seed gene in 184 cases of primary ESCC were detected by immunohistochemistry; The relationship between the expression level of seed genes and clinical significance were analyze. Results: A total of 244 DEGs were identified by comparing gene expression patterns between ESCC patients and the controls based on integrating dataset of GSE77861, GSE77861, GSE100942, GSE26886, GSE17351, GSE38129, GSE33426, GSE20347 and GSE23400; The CDKN3 were identified the seed gene of top cluster by use of PPI network and plug-in MCODE; The level of CDKN3 mRNA was significantly increased in ESCC patients compared to controls; The positive expression rate of CDKN3 protein in ESCC tissue samples was 32.0% and 61.4% in control, respectively, differences were statistically significant; There was significant correlation between the expression level of CDKN3 and lymph node metastasis or clinical staging of ESCC patients. Conclusion: Integrated transcriptomics is an efficient approach to system biology. By this procedure, our study improved the understanding of the transcriptome status of ESCC.

scholarly journals Integrated transcriptomics explored the cancer-promoting genes CDKN3 in esophageal squamous cell cancer

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wanpeng Wang ◽  
Kai Liao ◽  
Hao Chun Guo ◽  
Suqin Zhou ◽  
Ran Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Squamous Cell ◽  
Kinase Inhibitor ◽  
Expression Patterns ◽  
Cell Cancer ◽  
Expression Level ◽  
Clinical Staging ◽  
Tissue Samples ◽  
Seed Gene ◽  
Significant Difference

Abstract Background and objectives Each individual studies is limited to multi-factors and potentially lead to a significant difference of results among them. The present study aim to explore the critical genes related to the development of Esophageal squamous cell carcinoma (ESCC) by integrated transcriptomics and to investigate the clinical significance by experimental validation. Methods Datasets of protein-coding genes expression which involved in ESCC were downloaded from Gene Expression Omnibus (GEO) database. The “Robustrankaggreg” package in language was used for data integration, and the different expression genes (DEGs) were identified based the cut-off criteria as follows: adjust p-value < 0.05, |fold change (FC)| ≥ 1.5; The protein expression of seed gene in 184 cases of primary ESCC tissues and 50 tumor adjacent normal tissues (at least 5 cm away from the tumor, and defind as the controls) were detected by immunohistochemistry; The relationship between the expression level of seed genes and clinical parameter were analyze. Enumeration data were represented by frequency or percentage (%) and were tested by x2 test. The P value of less than 0.05 was considered statistically significant. Results A total of 244 DEGs were identified by comparing gene expression patterns between ESCC patients and the controls based on integrating dataset of GSE77861, GSE77861, GSE100942, GSE26886, GSE17351, GSE38129, GSE33426, GSE20347 and GSE23400; The Cyclin-dependent kinase inhibitor 3 (CDKN3) were identified the top 1 seed gene of top cluster by use of protein-protein Interaction network and plug-in Molecular Complex Detection; The level of CDKN3 mRNA was significantly increased in ESCC patients compared to controls; The positive expression rate of CDKN3 protein in ESCC tissue samples was 32 and 61.4% in control, respectively. The correlations between the expression level of CDKN3 and lymph node metastasis or clinical staging of ESCC patients are statistically significant. Conclusion Integrated transcriptomics is an efficient approach to system biology. By this procedure, our study improved the understanding of the transcriptome status of ESCC.

scholarly journals Assessment of Immunological Features in Muscle-Invasive Bladder Cancer Prognosis Using Ensemble Learning

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1624
Author(s):  
Christos G. Gavriel ◽  
Neofytos Dimitriou ◽  
Nicolas Brieu ◽  
Ines P. Nearchou ◽  
Ognjen Arandjelović ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Statistical Significance ◽  
Tnm Staging ◽  
Cancer Prognosis ◽  
Clinical Staging ◽  
Invasive Bladder Cancer ◽  
P Value ◽  
Muscle Invasive Bladder Cancer ◽  
Tissue Samples ◽  
Muscle Invasive

The clinical staging and prognosis of muscle-invasive bladder cancer (MIBC) routinely includes the assessment of patient tissue samples by a pathologist. Recent studies corroborate the importance of image analysis in identifying and quantifying immunological markers from tissue samples that can provide further insight into patient prognosis. In this paper, we apply multiplex immunofluorescence to MIBC tissue sections to capture whole-slide images and quantify potential prognostic markers related to lymphocytes, macrophages, tumour buds, and PD-L1. We propose a machine-learning-based approach for the prediction of 5 year prognosis with different combinations of image, clinical, and spatial features. An ensemble model comprising several functionally different models successfully stratifies MIBC patients into two risk groups with high statistical significance (p value < 1×10−5). Critical to improving MIBC survival rates, our method correctly classifies 71.4% of the patients who succumb to MIBC, which is significantly more than the 28.6% of the current clinical gold standard, the TNM staging system.

scholarly journals Evaluation of GNMT Gene Expression in Prostate Cancer Tissues using Real-Time PCR

2021 ◽  
Author(s):  
Niloofar Dehghani ◽  
Masoud Salehipour ◽  
Babak Javanmard
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Benign Prostatic Hyperplasia ◽  
Real Time ◽  
Real Time Pcr ◽  
Prostatic Hyperplasia ◽  
Expression Level ◽  
P Value ◽  
Cancer Tissue ◽  
Tissue Samples

Introduction: Prostate cancer is the second most common cancer and the leading cause of cancer-related deaths worldwide. In the present study, the expression level of glycine N-methyl transferase gene (GNMT) was investigated in prostate cancer tissue. The GNMT enzyme is encoded by the GNMT gene. Increased GNMT gene expression increases the conversion of glycine to sarcosine and results in the elevated levels of sarcosine in blood and urine. Methods: The expression level of GNMT gene in tissue samples of patients with prostate cancer was compared with those with benign prostatic hyperplasia using Real-Time PCR technique. Results: The GNMT gene expression level increased significantly in prostate cancer patients compared with those with benign prostatic hyperplasia (p-value <0.001). In addition, the expression level of GNMT gene was stage-dependent and  significant increases were observed in all stages of prostate cancer compared with those with benign prostatic hyperplasia (p-value <0.001). Conclusion: The concentration of sarcosine is controlled by GNMT and it seems that increasing the expression level of GNMT gene increases the level of sarcosine concentration. Thus, it appears that increased levels of GNMT expression occur in the early stages of prostate cancer. Therefore, periodic measurement of GNMT expression levels can detect prostate cancer before it forms a cancer cell and invades other tissues.

scholarly journals Gene expression of one important microRNA in blood and tissue samples of oral squamous cell carcinoma

2021 ◽  
Author(s):  
Naghmeh Emami ◽  
Naghmeh Bahrami ◽  
Masoumeh Mirzaei ◽  
Abdolreza Mohamadnia
Keyword(s):  
Gene Expression ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Peripheral Blood ◽  
Expression Level ◽  
P Value ◽  
Healthy Individuals ◽  
Tissue Samples

Introduction: Oral Squamous Cell Carcinoma (OSCC) is one of the most common oral malignancies, which accounts for 80-90% of malignant neoplasms of the oral cavity. MicroRNAs (miRNAs) are small RNA molecules that regulate post-transcriptional gene expression by targeting mRNAs. Materials and Methods: In this case-control study, 40 patients with oral squamous cell carcinoma and 40 healthy individuals as control were studied. Blood samples were collected from both groups. Also, 30 cancer tissue samples and 30 healthy tissue samples were prepared and evaluated. RNA was extracted from collected peripheral blood and tissue samples and evaluated for the expression level of miR-494 via real-time PCR technique. P. value values<0.05 were considered statistically significant. Results: The expression level of miR-494 in serum (peripheral blood) of patients with oral squa- mous cell carcinoma increased by 1.12 fold (P-value<0.001) compared with healthy individuals. Also, the expression level of miR-494 in samples of oral squamous cell carcinoma infected tissue showed a 1.28-fold increase compared to healthy tissue. Conclusion: The results of this study indicate an increase in the expression level (up-regula- tion) of miR-494 in oral squamous cell carcinoma. This biomarker can be used in screening and early detection of oral squamous cell carcinoma.

scholarly journals Expression Changes of the FOXE1 and Lncrna PTCSC2 Expression in Tumor Tissues Compared with Normal Tissues in Patients with Colorectal Cancer

2022 ◽  
Author(s):  
Marzieh Ghani Dehkordi ◽  
Maryam Peymani
Keyword(s):  
Colorectal Cancer ◽  
Tumor Tissue ◽  
Expression Patterns ◽  
Study Groups ◽  
Expression Level ◽  
P Value ◽  
Expression Levels ◽  
Normal Tissues ◽  
Tumor Tissues ◽  
Significant Difference

Introduction: In recent studies, methylation of FOXE1 in colorectal cancer has been reported as a diagnostic biomarker. In this study for the first time, the expression of FOXE1 and PTCSC2 in colorectal cancer was investigated and their expression patterns in two healthy and tumor tissues of patients were compared. Methods: In this study, 40 tumor tissues with colorectal cancer and 40 adjacent normal samples were collected. Total RNA was extracted and cDNA synthesis followed. Then, the specific genes for lncRNA PTCSC2 and FOXE1 were amplified. The results were statistically analyzed by Graph Pad Prism software and a T-test was used to compare the expression levels of lncRNA PTCSC2 and FOXE1 in the patients and healthy group; p-value less than 0.05 was considered significant difference criteria. Results: In this study, the FOXE1 expression level was significantly decreased in tumor tissue (p-value = 0.005), whereas the lncRNA PTCSC2 expression level in tumor tissue was not significantly changed (p-value = 0.65). In addition, the expression levels of FOXE1 and lncRNA PTCSC2 did not show a significant relation with disease progression and age of the patients. ROC curve for changes in FOXE1 and lncRNA PTCSC2 expression showed that theFOXE1 gene could be a relatively appropriate independent variable (p-value = 0.03) to differentiate between the two study groups. Conclusion: According to the results of this study, changes in FOXE1 gene expression were significantly reduced in tumor samples and can be used as a biomarker in tumor diagnosis in colorectal cancer.

Expression and Clinical Significance of β-Catenin in Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5010-5010
Author(s):  
Juan Li ◽  
Dian-Bao Zhang ◽  
Shao-kai Luo ◽  
Ying Zhao ◽  
Bei-Hui Huang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Clinical Significance ◽  
Healthy People ◽  
Expression Level ◽  
Stage Iii ◽  
Expression Levels ◽  
Mrna And Protein Expression ◽  
Expression Rate ◽  
The Relationship

Abstract OBJECTIVE: To detect the expression of β-catenin in mononuclears of bone marrow of healthy people, primary and relapsed/refractory multiple myeloma(MM), and analysis the clinical date and the curative effect of the MM patient, to open out the clinical significance of the expression of the β-catenin in MM. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and Wes tern blot were used to detect mRNA and protein expression of β-catenin in bone marrow samples of 12 primary MM patients, 14 relapsed/refractory MM patients, and 11 healthy people. RESULTS: The positive rates and the expression levels of β-catenin mRNA were significantly lower in healthy people than in MM patients (27.3% vs. 88.5%, 0.22±0.09 vs. 0.80±0.15, P &lt;0.01), the expression level of β-catenin mRNA(β-catenin/β-actin) was significantly lower in newly diagnosed patients than in MM patients (0.7196±0.11 vs. 0.8517±0.16, P &lt;0.05). β-catenin protein were not detected in all of the healthy people; while the positive rates of β-catenin was 69.2% in MM patients (P &lt;0.01), and its expression levels was significantly higher in relapsed/refractory patients than in primary patients (0.3231±0.11 vs. 0.2065±0.08, P&lt;0.05). In 10 primary MM patients which can be evaluated the curative effects, the expression rate in no response patients was significant lower than in response patients (14.3% vs. 100%, P &lt;0.05). To stage the patients, the statistics show the expression of β-catenin protein in Durie/Salmon stage III was significant higher than stageII(87.5% vs. 40%, P &lt;0.05) and in ISS stage III was significant higher than lor IIstage(100% vs. 45.5% or 33.3%). CONCLUSION: To analysis the relationship between β-catenin and β2-MG or serum LDH, we found the β-catenin protein was positive correlative with the expression level of β2-MG (r=0.688, P&lt;0.01). and serum LDH(r=0.502, P&lt;0.05).

scholarly journals HIF3A: A Potent Prognostic Biomarker in Different Kinds of Cancer

2021 ◽  
Author(s):  
Behnaz Yazdani ◽  
Hajar Sirous
Keyword(s):  
Expression Pattern ◽  
Metabolic Regulation ◽  
Expression Patterns ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Specific Expression ◽  
Tissue Samples ◽  
Expression Levels ◽  
Normal Tissues ◽  
Diagnostic Potential

Background: Hypoxia-inducible factors (HIFs) are transcription factors that get activated and stabilized in the heterodimerized form under hypoxic conditions. The three members of the HIF alpha factors share high structural similarity but have tissue-specific expression patterns. A majority of studies have reported the importance of the HIF1A and HIF2A activity in the survival, proliferation, metastatic potential, and metabolic regulation of hypoxic cancer cells. However, the importance of the expression pattern and activity of HIF3A in a variety of cancers remains unknown. Method and materials: The expression profile of 13 different types of The Cancer Genome Atlas (TCGA) cancer samples were downloaded, normalized and differential gene expression analysis (DGE) was performed to compare the expression pattern of HIF alpha family members in cancer and adjacent normal tissues, as well as at different stages and tumor-sizes. Receiver operating characteristic (ROC) test and survival analysis were carried out to estimate the diagnostic potential of HIF alpha isomers in different cancers, as well as the survival rate of patients with the varying expression levels of HIF alpha factors. Results: The expression status of HIF3A was notably less in all cancer samples in contrast to their adjacent normal tissues. The expression degree of HIF1A varied among distinct types of cancer and the expression degree of HIF2A was lower in nearly all types of cancers. The expression level of HIF alpha isomers did not significantly correlate with different sizes of tumor samples and stages of different tumor tissue samples. HIF3A had very weak diagnostic potential, while HIF2A had better diagnostic potential in most types of cancers compared to HIF1A. Patients who had a higher level of HIF3A had better survival, while the higher expression levels of HIF1A and HIF2A were associated with worse survival in many types of cancers. Conclusion: Our study shows the heterogenous expression pattern of HIF alpha subunits in distinctive kinds of cancers and the influence of HIF3A expression level in the survival of patients with varying types of cancers.

Comprehensive analysis of metastatic seminoma germ cell tumors shows divergent expression of immune-related pathways.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 506-506
Author(s):  
Tim Nestler ◽  
Friederike Haidl ◽  
Maike Wittersheim ◽  
Priya Dalvi ◽  
Pia Paffenholz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Cell ◽  
Molecular Mechanisms ◽  
Clinical Stage ◽  
Expression Patterns ◽  
Germ Cell Tumors ◽  
P Value ◽  
Testicular Germ Cell ◽  
Tissue Samples ◽  
Tumor Center

506 Background: Not much is known about the molecular mechanisms resulting in tumor progression and finally leading to metastasis in testicular germ cell tumor (TGCT). Only a few studies in some other tumor types have identified a limited set of genes, related to invasion, progression or metastases to be distinctly upregulated at the invasive tumor front in metastasized patients. However, systematic investigations are missing. Therefore, regional differences in the TGCT subtype seminomas were investigated to achieve a better understanding of the mechanisms involved in the metastatic process. Methods: Formalin-fixed paraffin embedded (FFPE) tissue samples of patients with clinical stage I disease, no adjuvant therapy and a relapse-free survival of at 2 years (n = 21), and patients showing metastasis (n = 14) were selected for the study. The tumor front (TF) and tumor center (TC) regions of each patient were determined and separately collected using laser capture microdissection. RNA was extracted and a multiplex gene expression analysis was performed on all TF and TC samples using nCounter technology of Nanostring. A panel of 770 transcripts was analyzed using the PanCancer Progression panel. Different bioinformatics tools were employed for analyzing the expression data. Results: Differential gene expression patterns were observed in the metastatic and non-metastatic patients, with respect to both the tumor front and tumor center regions. Ingenuity pathway analysis on the differentially expressed genes showed enrichment of tumor functions like migration, invasion, and angiogenesis at the TF as compared to the TC. Remarkably, prominent inflammatory and cancer related pathways such as IL-6 signaling, acute phase response signaling, NF-κB signaling and, dendritic cell maturation were significantly upregulated in the metastatic versus non-metastatic tumors (z-score > ± 2 and p-value < 0.05). Conclusions: This is the first study showing tumor heterogeneity in TGCTs. Evidently, IL-6 signalling was the most significantly upregulated pathway in the metastatic versus the non-metastatic patients, that could serve as a therapeutic target for personalized therapy.

scholarly journals LINC01089 functions as a ceRNA for miR-152-3p to inhibit non‐small lung cancer progression through regulating PTEN

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huixian Zhang ◽  
Hao Zhang ◽  
Xingya Li ◽  
Siyuan Huang ◽  
Qianqian Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Expression Level ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Protein Coding ◽  
Tensin Homolog ◽  
Pten Mrna

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3’UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

scholarly journals Downregulation of lncRNA ZNF582-AS1 due to DNA hypermethylation promotes clear cell renal cell carcinoma growth and metastasis by regulating the N(6)-methyladenosine modification of MT-RNR1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Wuping Yang ◽  
Kenan Zhang ◽  
Lei Li ◽  
Yawei Xu ◽  
Kaifang Ma ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Clinical Significance ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Level ◽  
Cell Renal Cell Carcinoma ◽  
Qrt Pcr

Abstract Background Emerging evidence confirms that lncRNAs (long non-coding RNAs) are potential biomarkers that play vital roles in tumors. ZNF582-AS1 is a novel lncRNA that serves as a potential prognostic marker of cancers. However, the specific clinical significance and molecular mechanism of ZNF582-AS1 in ccRCC (clear cell renal cell carcinoma) are unclear. Methods Expression level and clinical significance of ZNF582-AS1 were determined by TCGA-KIRC data and qRT-PCR results of 62 ccRCCs. DNA methylation status of ZNF582-AS1 promoter was examined by MSP, MassARRAY methylation and demethylation analysis. Gain-of-function experiments were conducted to investigate the biological roles of ZNF582-AS1 in the phenotype of ccRCC. The subcellular localization of ZNF582-AS1 was detected by RNA FISH. iTRAQ, RNA pull-down and RIP-qRT-PCR were used to identify the downstream targets of ZNF582-AS1. rRNA MeRIP-seq and MeRIP-qRT-PCR were utilized to examine the N(6)-methyladenosine modification status. Western blot and immunohistochemistry assays were used to determine the protein expression level. Results ZNF582-AS1 was downregulated in ccRCC, and decreased ZNF582-AS1 expression was significantly correlated with advanced tumor stage, higher pathological stage, distant metastasis and poor prognosis. Decreased ZNF582-AS1 expression was caused by DNA methylation at the CpG islands within its promoter. ZNF582-AS1 overexpression inhibited cell proliferative, migratory and invasive ability, and increased cell apoptotic rate in vitro and in vivo. Mechanistically, we found that ZNF582-AS1 overexpression suppressed the N(6)-methyladenosine modification of MT-RNR1 by reducing rRNA adenine N(6)-methyltransferase A8K0B9 protein level, resulting in the decrease of MT-RNR1 expression, followed by the inhibition of MT-CO2 protein expression. Furthermore, MT-RNR1 overexpression reversed the decreased MT-CO2 expression and phenotype inhibition of ccRCC induced by increased ZNF582-AS1 expression. Conclusions This study demonstrates for the first time that ZNF582-AS1 functions as a tumor suppressor gene in ccRCC and ZNF582-AS1 may serve as a potential biomarker and therapeutic target of ccRCC.

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