scholarly journals UBE2V2 promotes metastasis by regulating EMT and predicts a poor prognosis in lung adenocarcinoma.

2021 ◽  
Author(s):  
Zheng Yang ◽  
Qiang Xue ◽  
Caishen Du ◽  
Miaosen Zhen ◽  
Jianxun Xu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Patient Survival ◽  
Immunohistochemical Analysis ◽  
S Phase ◽  
Clinicopathological Factors ◽  
Migration Ability ◽  
Survival Prognosis ◽  
Tissue Samples ◽  
Normal Tissues ◽  
Ubiquitin Conjugating Enzymes

Abstract Background: Belonging to the ubiquitin-conjugating enzymes (E2s) family, UBE2V2 demonstrated a remarkable tumourigenic ability in many kinds of cancers. However, the interrelationship between UBE2V2 expression and morbidity of lung adenocarcinoma (LUAD) is still unknown. Methods: By using TCGA predictions and clinical tissue samples, we assessed the expression of UBE2V2 mRNA and protein in LUAD and analyzed its relationship with different clinicopathological factors as well as survival prognosis. Besides, we further studied the EMT signaling pathway that promotes LUAD metastasis and other phenotypic experiments by using lentivirus to transfect LUAD cells. Results: Our research results showed that compared with normal tissues, the expression of UBE2V2 mRNA and protein in LUAD was significantly increased (P<0.001). UBE2V2 might be considered as an independent prognostic molecule for LUAD patient survival prognosis based on TCGA prediction (HR:1.497 P=0.012) and immunohistochemical analysis (ICH) (HR:1.842 P=0.042). ICH showed that UBE2V2 was related to the following clinicopathological factors, including gender (P=0.021), stage (P=0.042), lymph node metastasis (P=0.021) and differentiated degree (P=0.015). Finally, knockdown of UBE2V2 significantly reduced the migration ability by regulating the EMT pathway. The knockdown of UBE2V2 inhibited cells proliferation, reduced the proportion of cells in S phase and promoted cell apoptosis. Interestingly, UBE2V2 expression is negatively correlated with B cells, CD4 + T cells, macrophages and dendritic cells. Conclusions: In summary, UBE2V2 might play an important role in the progression of LUAD.

scholarly journals Investigation on Potential Correlation Between Small Nuclear Ribonucleoprotein Polypeptide A and Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Maoxi Yuan ◽  
Chunmei Yu ◽  
Xin Chen ◽  
Yubing Wu
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Rna Splicing ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
M2 Macrophage ◽  
Survival Prognosis ◽  
Normal Tissues ◽  
Small Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

SNRPA (small nuclear ribonucleoprotein polypeptide A) gene is essential for the pre-mRNA splicing process. Using the available datasets of TCGA or GEO, we aimed at exploring the potential association between the SNRPA gene and lung cancer by several online tools (such as GEIPA2, MEXPRESS, Oncomine) and bioinformatics analysis software (R or GSEA). SNRPA was highly expressed in the tissues of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma tissue (LUSC), compared with control tissues. The high SNRPA expression was associated with a poor survival prognosis of LUAD cases, while the genetic alteration within SNRPA was linked to the overall survival prognosis of LUSC cases. There was a potential correlation between promoter methylation and the expression of SNRPA for LUAD. Compared with normal tissues, we observed a higher phosphorylation level at the S115 site of SNRPA protein (NP_004587.1) (p = 0.002) in the primary LUAD tissues. The potential ATR kinase of the S115 site was predicted. Besides, SNRPA expression in lung cancer was negatively correlated with the infiltration level of M2 macrophage but positively correlated with that of Follicular B helper T cells, in both LUAD and LUSC. The enrichment analysis of SNRPA-correlated genes showed that cell cycle and ubiquitin mechanism-related issues were mainly observed for LUAD; however, RNA splicing-related cellular issues were mainly for LUSC. In summary, the SNRPA gene was identified as a potential prognosis biomarker of lung cancer, especially lung adenocarcinoma, which sheds new light on the association between the spliceosomal complex component and tumorigenesis.

Overexpression of cyclin E messenger ribonucleic acid in nasopharyngeal carcinoma correlates with poor prognosis

2009 ◽  
Vol 123 (9) ◽  
pp. 1021-1026 ◽  
Author(s):  
M-T Ko ◽  
C-Y Su ◽  
S-C Huang ◽  
C-H Chen ◽  
C-F Hwang
Keyword(s):  
Overall Survival ◽  
Nasopharyngeal Carcinoma ◽  
Ribonucleic Acid ◽  
Cyclin E ◽  
Immunohistochemical Analysis ◽  
S Phase ◽  
Fold Change ◽  
Tissue Samples ◽  
Messenger Ribonucleic Acid ◽  
Nasopharyngeal Tissue

AbstractAims:S-phase kinase-associated protein 2 is required for the degradation of p27 protein, which is a negative regulator of cyclin E/cyclin-dependent kinase 2 complex. The present study examined the expression of cyclin E, S-phase kinase-associated protein 2 and p27 protein in nasopharyngeal carcinoma.Methods:Tissue from 35 cases of nasopharyngeal carcinoma and 10 normal nasopharyngeal tissue samples underwent reverse polymerase chain reaction to detect messenger ribonucleic acid. Immunohistochemical analysis was performed on 29 nasopharyngeal tissue samples in order to detect protein expression.Results:Messenger ribonucleic acid expression in the nasopharyngeal carcinoma tissue samples analysed indicated a 1.75-fold change in the amount of S-phase kinase-associated protein 2, a 0.34-fold change in the amount of cyclin E and a 0.31-fold change in the amount of p27 protein, compared with positive controls. High levels of cyclin E significantly correlated with late-stage nasopharyngeal carcinoma (p = 0.009) and a poor overall survival (p = 0.010). Immunohistochemical analysis indicated positive expression of S-phase kinase-associated protein 2 in 16/29 nasopharyngeal tissue samples (55 per cent), of cyclin E in 13/29 samples (45 per cent) and of p27 protein in 17/29 (59 per cent) samples.Conclusions:Overexpression of cyclin E messenger ribonucleic acid showed an adverse prognostic significance, correlating with an advanced stage of nasopharyngeal carcinoma and a low overall survival rate.

scholarly journals Upregulation of Long Non-Coding RNA GCC2-AS1 Facilitates Malignant Phenotypes and Correlated With Unfavorable Prognosis for Lung Adenocarcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Fengqiang Yu ◽  
Mingqiang Liang ◽  
Weidong Wu ◽  
Yu Huang ◽  
Jiantao Zheng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Noncoding Rna ◽  
Prognostic Value ◽  
Malignant Tumors ◽  
Biological Effects ◽  
Enrichment Analysis ◽  
Tissue Samples ◽  
Independent Prognostic Marker ◽  
Normal Tissues

BackgroundThe role played by long noncoding RNA GCC2-AS1 in primary malignant tumors remains poorly understood. This study aimed to determine the expression levels and evaluate the clinical significance and biological effects of GCC2-AS1 in lung adenocarcinoma (LUAD).MethodsWe used data obtained from tissue samples and the TCGA database to determine the levels of GCC2-AS1 expression LUAD patients, and the prognostic value of those levels. Functional experiments were performed to investigate the effect of GCC2-AS1 on LUAD cells. Genes that were differentially expressed in GCC2-AS1-low and -high groups were analyzed by an enrichment analysis. Additionally, a nomogram model was created and subgroup analyses were performed to further determine the prognostic value of GCC2-AS1 in LUAD.ResultsGCC2-AS1 expression was significantly upregulated in lung adenocarcinoma tissues as compared with normal tissues. Depletion of GCC2-AS1 inhibited the proliferation and invasion of LUAD cells in vitro. An elevated level of GCC2-AS1 was strongly correlated with shorter overall survival time and was identified as an independent prognostic marker for LUAD patients. Enrichment analyses conducted using GO, KEGG, and GSEA databases were performed to identify biological pathways that might involve GCC2-AS1. Several subgroups were found to have a significant prognostic value for patients in the GCC2-AS1-low and -high groups.ConclusionsOur findings suggest that GCC2-AS1 can serve as a diagnostic and prognostic biomarker for LUAD patients.

scholarly journals Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3045
Author(s):  
Euiyoung Oh ◽  
Jun-Hyeong Kim ◽  
JungIn Um ◽  
Da-Woon Jung ◽  
Darren R. Williams ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cancer Patient ◽  
Immune Cells ◽  
Renal Cell ◽  
Prognostic Markers ◽  
Patient Survival ◽  
Survival Outcome ◽  
Normal Tissues ◽  
Genome Wide ◽  
The Relationship

The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.

Transmembrane p24 Trafficking Protein 2 Regulates Inflammation Through the TLR4/NF-κB Signaling Pathway in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Longhua Feng ◽  
Pengjiang Cheng ◽  
Zhengyun Feng ◽  
Xiaoyu Zhang
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Inflammatory Factors ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
New Strategy

Abstract Background: To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD in vitro and in vivo.Methods: TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, and pan-cancer systems were used to predict the potential function of TMED2. Western blotting and immunohistochemistry were performed to analyze TMED2 expression in different tissues or cell lines. The proliferation, development, and apoptosis of LUAD were observed using a lentivirus-mediated TMED2 knockdown. Bioinformatics and western blot analysis of TMED2 against inflammation via the TLR4/NF-κB signaling pathway were conducted. Results: TMED2 expression in LUAD tumor tissues was higher than that in normal tissues and positively correlated with poor survival in lung cancer and negatively correlated with apoptosis in LUAD. The expression of TMED2 was higher in tumors or HCC827 cells. TMED2 knockdown inhibited LUAD development in vitro and in vivo and increased the levels of inflammatory factors via the TLR4/NF-κB signaling pathway. TMED2 was correlated with TME, immune score, TME-associated immune cells, their target markers, and some mechanisms and pathways, as determined using the TIMER2.0, GO, and KEGG assays.Conclusions: TMED2 may regulate inflammation in LUAD through the TLR4/NF-κB signaling pathway, and enhance the proliferation, development, and prognosis of LUAD by regulating inflammation, which provide a new strategy for treating LUAD by regulating inflammation.

Identification of the signature genes and network of Reactive Oxygen Species (ROS) related genes and DNA repair genes in Lung Adenocarcinoma (LUAD)

2021 ◽  
Author(s):  
Ye Zhao ◽  
Hai-Ming Feng ◽  
Xiao-Ping Wei ◽  
Wei-Jian Yan ◽  
Bin Li ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Dna Repair ◽  
Tumor Cell ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Patient Survival ◽  
Reactive Oxygen ◽  
Dna Repair Genes ◽  
Oxygen Species ◽  
Repair Genes

Abstract Reactive Oxygen Species (ROS) are present in high amount in patients with tumors, and these ROS can kill and destroy tumor cells. Thus, tumor cells upregulate ROS-related genes to protect themselves and reduce their destruction. Cancer cells already damaged by ROS can be repaired by expressing DNA repair genes consequently promoting their proliferation. In this work, lung adenocarcinoma (LUAD) transcriptome data in the TCGA database was analyzed and samples were clustered into 5 ROS-related categories and 6 DNA repair categories. Survival analysis revealed a significant difference in patient survival between the two classification methods. In addition, the samples corresponding to the two categories overlap, thus, the gene expression profile of the same sample with different categories and survival prognosis was further explored, and the connection between ROS-related genes and DNA repair genes was investigated. The interactive sample recombination classification was used, revealing that the patient's prognosis was worse when the ROS-related genes and DNA repair genes were expressed at the same time. The further research on the potential regulatory network of the two categories of genes and the correlation analysis revealed that ROS-related genes and DNA repair genes have a mutual regulatory relationship. The ROS-related genes NQO1, TXNRD1, and PRDX4 could establish links with other DNA repair genes through the DNA repair gene NEIL3, thereby increasing the growth of tumor cells and balancing the level of ROS, leading to tumor cell death and constant damage to the tumor cell repair system, thus prolonging patient survival. Thus, targeting ROS-related genes and DNA repair genes might be a promising strategy in the treatment of LUAD. Finally, a survival prognostic model of ROS-related genes and DNA repair genes was established (TERT, PRKDC, PTTG1, SMUG1, TXNRD1, CAT, H2AFX and PFKP), the risk score might be used as an independent prognostic factor in LUAD patients.

Abstract P195: No Functional Nerve Recovery To 6 Months Post Renal Denervation With Rf Energy In A Normotensive Pig Model

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Andrew Sharp ◽  
Stefan Tunev ◽  
Markus P Schlaich ◽  
David P LEE ◽  
Aloke Finn ◽  
...  
Keyword(s):  
Animal Studies ◽  
Renal Denervation ◽  
Blood Pressure Reduction ◽  
Immunohistochemical Analysis ◽  
Swine Model ◽  
Renal Nerve ◽  
Tissue Samples ◽  
Axon Density ◽  
Rf Energy

Background: The safety and efficacy of catheter-based radio frequency (RF) renal denervation (RDN) have been demonstrated in randomized, sham-controlled trials. Long-term durability of blood pressure reduction following RDN has also been demonstrated by all-comer registries, although published pre-clinical reports of functional renal nerve regrowth are not consistent. We quantified the processes that support RDN procedural durability utilizing animal models. Methods: Animal studies were conducted in accordance with published guidelines. RDN was performed (4 lesions in the main renal artery) in normotensive swine using the Symplicity Spyral™ RDN system (Medtronic, Santa Rosa, CA, USA). Two additional groups not undergoing RDN served as control. Serial histological tissue samples were obtained in separate groups at 7 (n=12/group) and 180 (N=16/group) days post-procedure in all animals followed by bioanalytical quantification of cortical norepinephrine (NE) levels and immunohistochemical analysis of renal cortical axon density in matched samples. Results: Renal cortical axon density and NE levels were significantly reduced at 7 days and persisted through 180 days following RDN compared with control ( Figure ). Nerve fibrosis and necrosis were observed in the region of ablation, while nerve body atrophy was apparent distal to ablation location at 180 days. Conclusions: Reductions in both NE and renal cortical axon density were sustained at 7 and 180 days post-RDN procedure using RF renal denervation in a normotensive swine model. These data confirm and extend other pre-clinical and clinical evidence of long-term durability of the RDN procedure using RF energy.

scholarly journals DPYSL2 as potential diagnostic and prognostic biomarker linked to immune infiltration in lung adenocarcinoma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang-Jie Wu ◽  
Ai-Tao Nai ◽  
Gui-Cheng He ◽  
Fei Xiao ◽  
Zhi-Min Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Roc Curve ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
List Type ◽  
Gene Set Enrichment ◽  
Gene Set ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background Dihydropyrimidinase like 2 (DPYSL2) has been linked to tumor metastasis. However, the function of DPSY2L in lung adenocarcinoma (LUAD) is yet to be explored. Methods Herein, we assessed DPYSL2 expression in various tumor types via online databases such as Oncomine and Tumor Immune Estimation Resource (TIMER). Further, we verified the low protein and mRNA expressions of DPYSL2 in LUAD via the ULCAN, The TCGA and GEPIA databases. We applied the ROC curve to examine the role of DPYSL2 in diagnosis. The prognostic significance of DPYSL2 was established through the Kaplan–Meier plotter and the Cox analyses (univariate and multivariate). TIMER was used to explore DPYSL2 expression and its connection to immune infiltrated cells. Through Gene Set Enrichment Analysis, the possible mechanism of DPYSL2 in LUAD was investigated. Results In this study, database analysis revealed lower DPYSL2 expression in LUAD than in normal tissues. The ROC curve suggested that expression of DPYSL2 had high diagnostic efficiency in LUAD. The DPYSL2 expression had an association with the survival time of LUAD patients in the Kaplan–Meier plotter and the Cox analyses. The results from TIMER depicted a markedly positive correlation of DPYSL2 expression with immune cells infiltrated in LUAD, such as macrophages, dendritic cells, CD4+ T cells, and neutrophils. Additionally, many gene markers for the immune system had similar positive correlations in the TIMER analysis. In Gene Set Enrichment Analysis, six immune-related signaling pathways were associated with DPYSL2. Conclusions In summary, DPYSL2 is a novel biomarker with diagnostic and prognostic potential for LUAD as well as an immunotherapy target. Highlights Expression of DPYSL2 was considerably lower in LUAD than in normal tissues. Investigation of multiple databases showed a high diagnostic value of DPYSL2 in LUAD. DPYSL2 can independently predict the LUAD outcomes. Immune-related mechanisms may be potential ways for DPYSL2 to play a role in LUAD.

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