Abnormal Expression of EPB41L1 in Colon Adenocarcinoma and Effect on Prognosis

Abstract Background: Colon adenocarcinoma (COAD) is the most common pathological type of colorectal cancer (CRC) and further study of the molecular mechanism will help to improve the quality of life of patients with COAD. Erythrocyte membrane protein band 4.1 like 1(EPB41L1), a gene encoding protein 4.1N, has been reported to be closely associated with tumorigenesis and progression. However, the role of EPB41L1 in COAD is largely unknown and remains to be fully studied.Methods: In this study, we analyzed the mRNA expression of EPB41L1 in COAD through the Oncomine and GEO databases. Then, the relative expressions of EPB41L1 across the sub-groups of COAD were performed by the UALCAN data portal. Next, we investigated the prognostic value of EPB41L1 in COAD patients by using the UALCAN and HPA online databases. Further, the mutation of EPB41L1 in COAD was analyzed by c-Bioportal. The co-expression genes of EPB41L1 in COAD were displayed from the LinkedOmics database, and function enrichment analysis was analyzed by DAVID. The co-expression gene network was constructed through the STRING database, and the MCODE plug-in of which was used to build the gene modules, both of them were visualized by Cytoscape software. Finally, the pathway enrichment of the top modular genes in the co-expression gene network was analyzed by DAVID.Results: The results revealed that EPB41L1 is significantly upregulated with the development of COAD, leading to a poor prognosis. There are mutations in the EPB41L1 gene, but it has no significant effect on the prognosis of COAD. Moreover, the genes correlated with EPB41L1 in COAD, identified in the most highly connected sub-network, were enriched in the cell cycle. Conclusions: In summary, the above results suggest that EPB41L1 was significantly upregulated in the COAD tissues and the high expression level of EPB41L1 predicts a poor prognosis of COAD patients. Therefore, we suggest that EPB41L1 can be a potential candidate biomarker for the diagnosis and prognosis of COAD.

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BIRC7 and STC2 expression is associated with tumorigenesis and poor outcome in extrahepatic cholangiocarcinoma

10.21203/rs.2.24457/v1 ◽

2020 ◽

Author(s):

Jiequn Li ◽

Zhulin Yang ◽

Shengfu Huang ◽

Daiqiang Li

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Biliary Tract ◽

Poor Prognosis ◽

Diagnostic And Prognostic Application ◽

Tumor Biomarker ◽

Extrahepatic Cholangiocarcinoma ◽

Node Metastasis ◽

Diagnosis And Prognosis ◽

Tumorigenesis And Progression

Abstract Background: Extrahepatic cholangiocarcinoma (EHCC) is a highly aggressive epithelial malignancy and has a poor prognosis for their insensitivity to therapies and difficulty in detection. Novel targets and biomarkers are urgently needed to develop for functional, diagnostic and prognostic application on EHCC. Methods: 100 EHCC tissues，30 peritumoral tissues, 10 adenoma and 15 normal biliary tract tissues were assayed using EnVision immunohistochemistry. Results: The expression of BIRC7 and STC2 proteins were higher in EHCC tissues than those in peritumoral tissues, adenoma and normal biliary tract tissues. The positive rates of BIRC7 and STC2 expression were significantly higher in cases with lymph node metastasis, invasion to surrounding tissues/organs, and TNM stage III and/or IV and unable to undergo resection (biopsy only). Kaplan-Meier survival curves demonstrated that the overall survival of positive-BIRC7 or positive-STC2 patients was significantly lower than those of negative-BIRC7 or negative-STC2, respectively. Cox-proportional regression analysis demonstrated that positive-BIRC7 and positive-STC2 expression, along with poor differentiation of EHCC, tumor size >3cm, lymph node metastasis, invasion to surrounding tissues/organs and unable to undergo resection are independent prognostic factors of EHCC patients. Conclusions: BIRC7 and STC2 are involved in the tumorigenesis and progression of EHCC, and positive expression of BIRC7 and STC2 are associated with poor prognosis in patients with EHCC. BIRC7 and STC2 might be a potential tumor biomarker for EHCC diagnosis and prognosis.

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Identification of novel autophagy-related lncRNAs associated with a poor prognosis of colon adenocarcinoma through bioinformatics analysis

Scientific Reports ◽

10.1038/s41598-021-87540-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Dejun Wu ◽

Zhenhua Yin ◽

Yisheng Ji ◽

Lin Li ◽

Yunxin Li ◽

...

Keyword(s):

High Risk ◽

Poor Prognosis ◽

Notch Pathway ◽

Colon Adenocarcinoma ◽

High Risk Group ◽

The Cancer Genome Atlas ◽

Future Research ◽

Risk Patients ◽

Cancer Genome Atlas ◽

Immune Score

AbstractLncRNAs play a pivotal role in tumorigenesis and development. However, the potential involvement of lncRNAs in colon adenocarcinoma (COAD) needs to be further explored. All the data used in this study were obtained from The Cancer Genome Atlas database, and all analyses were conducted using R software. Basing on the seven prognosis-related lncRNAs finally selected, we developed a prognosis-predicting model with powerful effectiveness (training cohort, 1 year: AUC = 0.70, 95% Cl = 0.57–0.78; 3 years: AUC = 0.71, 95% Cl = 0.6–0.8; 5 years: AUC = 0.76, 95% Cl = 0.66–0.87; validation cohort, 1 year: AUC = 0.70, 95% Cl = 0.58–0.8; 3 years: AUC = 0.73, 95% Cl = 0.63–0.82; 5 years: AUC = 0.68, 95% Cl = 0.5–0.85). The VEGF and Notch pathway were analyzed through GSEA analysis, and low immune and stromal scores were found in high-risk patients (immune score, cor = − 0.15, P < 0.001; stromal score, cor = − 0.18, P < 0.001) , which may partially explain the poor prognosis of patients in the high-risk group. We screened lncRNAs that are significantly associated with the survival of patients with COAD and possibly participate in autophagy regulation. This study may provide direction for future research.

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DNA Methylation Profiling for the Diagnosis and Prognosis of Patients with Nontuberculous Mycobacterium Lung Disease

Current Issues in Molecular Biology ◽

10.3390/cimb43020038 ◽

2021 ◽

Vol 43 (2) ◽

pp. 501-512

Author(s):

Jee Youn Oh ◽

Young Kyung Ko ◽

Jeong-An Gim

Keyword(s):

Dna Methylation ◽

Lung Disease ◽

Poor Prognosis ◽

Wnt Signaling Pathway ◽

Fold Change ◽

Nontuberculous Mycobacterium ◽

Healthy Controls ◽

Log2 Fold Change ◽

Diagnosis And Prognosis ◽

Ntm Lung Disease

The incidence of nontuberculous Mycobacterium (NTM) lung disease is rapidly increasing; however, its diagnosis and prognosis remain unclear while selecting patients who will respond to appropriate treatment. Differences in DNA methylation patterns between NTM patients with good or poor prognosis could provide important therapeutic targets. We used the Illumina MethylationEPIC (850k) DNA methylation microarray to determine the pattern between differentially methylated regions (DMRs) in NTM patients with good or poor prognosis (n = 4/group). Moreover, we merged and compared 20 healthy controls from previous Illumina Methylation450k DNA methylation microarray data. We selected and visualized the DMRs in the form of heatmaps, and enriched terms associated with these DMRs were identified by functional annotation with the “pathfinder” package. In total, 461 and 293 DMRs (|Log2 fold change| > 0.1 and p < 0.03) were more methylated in patients with four poor and four good prognoses, respectively. Furthermore, 337 and 771 DMRs (|Log2 fold change| > 0.08 and p < 0.001) were more methylated in eight NTM patients and 20 healthy controls, respectively. TGFBr1 was significantly less methylated, whereas HLA-DR1 and HLA-DR5 were more methylated in patients with poor prognosis (compared to those with good prognosis). LRP5, E2F1, and ADCY3 were the top three less-methylated genes in NTM patients (compared with the controls). The mTOR and Wnt signaling pathway-related genes were less methylated in patients with NTM. Collectively, genes related to Th1-cell differentiation, such as TGFBr1 and HLA-DR, may be used as biomarkers for predicting the treatment response in patients with NTM lung disease.

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Novel Epigenetic Eight-Gene Signature Predictive of Poor Prognosis and MSI-Like Phenotype in Human Metastatic Colorectal Carcinomas

Cancers ◽

10.3390/cancers13010158 ◽

2021 ◽

Vol 13 (1) ◽

pp. 158

Author(s):

Valentina Condelli ◽

Giovanni Calice ◽

Alessandra Cassano ◽

Michele Basso ◽

Maria Grazia Rodriquenz ◽

...

Keyword(s):

Gene Expression ◽

Poor Prognosis ◽

Cpg Island ◽

Colon Adenocarcinoma ◽

Gene Signature ◽

Gene Expression Omnibus ◽

The Cancer Genome Atlas ◽

Cpg Island Methylator Phenotype ◽

Prognostic Information ◽

Global Methylation

Epigenetics is involved in tumor progression and drug resistance in human colorectal carcinoma (CRC). This study addressed the hypothesis that the DNA methylation profiling may predict the clinical behavior of metastatic CRCs (mCRCs). The global methylation profile of two human mCRC subgroups with significantly different outcome was analyzed and compared with gene expression and methylation data from The Cancer Genome Atlas COlon ADenocarcinoma (TCGA COAD) and the NCBI GENE expression Omnibus repository (GEO) GSE48684 mCRCs datasets to identify a prognostic signature of functionally methylated genes. A novel epigenetic signature of eight hypermethylated genes was characterized that was able to identify mCRCs with poor prognosis, which had a CpG-island methylator phenotype (CIMP)-high and microsatellite instability (MSI)-like phenotype. Interestingly, methylation events were enriched in genes located on the q-arm of chromosomes 13 and 20, two chromosomal regions with gain/loss alterations associated with adenoma-to-carcinoma progression. Finally, the expression of the eight-genes signature and MSI-enriching genes was confirmed in oxaliplatin- and irinotecan-resistant CRC cell lines. These data reveal that the hypermethylation of specific genes may provide prognostic information that is able to identify a subgroup of mCRCs with poor prognosis.

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Overexpressed XRCC2 as an independent risk factor for poor prognosis in glioma patients

Molecular Medicine ◽

10.1186/s10020-021-00316-0 ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Zhendong Liu ◽

Wang Zhang ◽

Xingbo Cheng ◽

Hongbo Wang ◽

Lu Bian ◽

...

Keyword(s):

Risk Factor ◽

Expression Pattern ◽

Poor Prognosis ◽

Independent Risk Factor ◽

Cox Regression ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Cellular Mechanisms ◽

Molecular Features ◽

Meta Analyses

Abstract Background XRCC2, a homologous recombination-related gene, has been reported to be associated with a variety of cancers. However, its role in glioma has not been reported. This study aimed to find out the role of XRCC2 in glioma and reveal in which glioma-specific biological processes is XRCC2 involved based on thousands of glioma samples, thereby, providing a new perspective in the treatment and prognostic evaluation of glioma. Methods The expression characteristics of XRCC2 in thousands of glioma samples from CGGA and TCGA databases were comprehensively analyzed. Wilcox or Kruskal test was used to analyze the expression pattern of XRCC2 in gliomas with different clinical and molecular features. The effect of XRCC2 on the prognosis of glioma patients was explored by Kaplan–Meier and Cox regression. Gene set enrichment analysis (GSEA) revealed the possible cellular mechanisms involved in XRCC2 in glioma. Connectivity map (CMap) was used to screen small molecule drugs targeting XRCC2 and the expression levels of XRCC2 were verified in glioma cells and tissues by RT-qPCR and immunohistochemical staining. Results We found the overexpression of XRCC2 in glioma. Moreover, the overexpressed XRCC2 was associated with a variety of clinical features related to prognosis. Cox and meta-analyses showed that XRCC2 is an independent risk factor for the poor prognosis of glioma. Furthermore, the results of GSEA indicated that overexpressed XRCC2 could promote malignant progression through involved signaling pathways, such as in the cell cycle. Finally, doxazosin, quinostatin, canavanine, and chrysin were identified to exert anti-glioma effects by targeting XRCC2. Conclusions This study analyzed the expression pattern of XRCC2 in gliomas and its relationship with prognosis using multiple datasets. This is the first study to show that XRCC2, a novel oncogene, is significantly overexpressed in glioma and can lead to poor prognosis in glioma patients. XRCC2 could serve as a new biomarker for glioma diagnosis, treatment, and prognosis evaluation, thus bringing new insight into the management of glioma.

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Genome-wide association study and gene network analyses reveal potential candidate genes for high night temperature tolerance in rice

Scientific Reports ◽

10.1038/s41598-021-85921-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Raju Bheemanahalli ◽

Montana Knight ◽

Cherryl Quinones ◽

Colleen J. Doherty ◽

S. V. Krishna Jagadish

Keyword(s):

Grain Size ◽

Candidate Genes ◽

Gene Network ◽

Genome Wide Association ◽

Potential Candidate ◽

Genetic Loci ◽

Stay Green ◽

Yield And Quality ◽

Genome Wide ◽

Wide Range

AbstractHigh night temperatures (HNT) are shown to significantly reduce rice (Oryza sativa L.) yield and quality. A better understanding of the genetic architecture of HNT tolerance will help rice breeders to develop varieties adapted to future warmer climates. In this study, a diverse indica rice panel displayed a wide range of phenotypic variability in yield and quality traits under control night (24 °C) and higher night (29 °C) temperatures. Genome-wide association analysis revealed 38 genetic loci associated across treatments (18 for control and 20 for HNT). Nineteen loci were detected with the relative changes in the traits between control and HNT. Positive phenotypic correlations and co-located genetic loci with previously cloned grain size genes revealed common genetic regulation between control and HNT, particularly grain size. Network-based predictive models prioritized 20 causal genes at the genetic loci based on known gene/s expression under HNT in rice. Our study provides important insights for future candidate gene validation and molecular marker development to enhance HNT tolerance in rice. Integrated physiological, genomic, and gene network-informed approaches indicate that the candidate genes for stay-green trait may be relevant to minimizing HNT-induced yield and quality losses during grain filling in rice by optimizing source-sink relationships.

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The Schizosaccharomyces pombe cho1+ Gene Encodes a Phospholipid Methyltransferase

Genetics ◽

10.1093/genetics/150.2.553 ◽

1998 ◽

Vol 150 (2) ◽

pp. 553-562

Author(s):

Margaret I Kanipes ◽

John E Hill ◽

Susan A Henry

Keyword(s):

Saccharomyces Cerevisiae ◽

Sequence Analysis ◽

Schizosaccharomyces Pombe ◽

Gene Disruption ◽

Structure And Function ◽

Biosynthetic Enzyme ◽

Gene Encoding ◽

Complementation Groups ◽

Eukaryotic Organisms ◽

And Function

Abstract The isolation of mutants of Schizosaccharomyces pombe defective in the synthesis of phosphatidylcholine via the methylation of phosphatidylethanolamine is reported. These mutants are choline auxotrophs and fall into two unlinked complementation groups, cho1 and cho2. We also report the analysis of the cho1+ gene, the first structural gene encoding a phospholipid biosynthetic enzyme from S. pombe to be cloned and characterized. The cho1+ gene disruption mutant (cho1Δ) is viable if choline is supplied and resembles the cho1 mutants isolated after mutagenesis. Sequence analysis of the cho1+ gene indicates that it encodes a protein closely related to phospholipid methyltransferases from Saccharomyces cerevisiae and rat. Phospholipid methyltransferases encoded by a rat liver cDNA and the S. cerevisiae OPI3 gene are both able to complement the choline auxotrophy of the S. pombe cho1 mutants. These results suggest that both the structure and function of the phospholipid N-methyltransferases are broadly conserved among eukaryotic organisms.

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Mutations in GDAP1 Influence Structure and Function of the Trans-Golgi Network

International Journal of Molecular Sciences ◽

10.3390/ijms22020914 ◽

2021 ◽

Vol 22 (2) ◽

pp. 914

Author(s):

Katarzyna Binięda ◽

Weronika Rzepnikowska ◽

Damian Kolakowski ◽

Joanna Kaminska ◽

Andrzej Antoni Szczepankiewicz ◽

...

Keyword(s):

Golgi Apparatus ◽

Experimental Therapy ◽

Negative Effects ◽

Gene Encoding ◽

Charcot Marie Tooth Disease ◽

Terra Incognita ◽

And Function ◽

Golgi Network ◽

Cell Phenotypes ◽

Tooth Disease

Charcot-Marie-Tooth disease (CMT) is a heritable neurodegenerative disease that displays great genetic heterogeneity. The genes and mutations that underlie this heterogeneity have been extensively characterized by molecular genetics. However, the molecular pathogenesis of the vast majority of CMT subtypes remains terra incognita. Any attempts to perform experimental therapy for CMT disease are limited by a lack of understanding of the pathogenesis at a molecular level. In this study, we aim to identify the molecular pathways that are disturbed by mutations in the gene encoding GDAP1 using both yeast and human cell, based models of CMT-GDAP1 disease. We found that some mutations in GDAP1 led to a reduced expression of the GDAP1 protein and resulted in a selective disruption of the Golgi apparatus. These structural alterations are accompanied by functional disturbances within the Golgi. We screened over 1500 drugs that are available on the market using our yeast-based CMT-GDAP1 model. Drugs were identified that had both positive and negative effects on cell phenotypes. To the best of our knowledge, this study is the first report of the Golgi apparatus playing a role in the pathology of CMT disorders. The drugs we identified, using our yeast-based CMT-GDAP1 model, may be further used in translational research.

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Yeast ribosomal protein L1 is required for the stability of newly synthesized 5S rRNA and the assembly of 60S ribosomal subunits

Molecular and Cellular Biology ◽

10.1128/mcb.13.5.2835-2845.1993 ◽

1993 ◽

Vol 13 (5) ◽

pp. 2835-2845

Author(s):

M Deshmukh ◽

Y F Tsay ◽

A G Paulovich ◽

J L Woolford

Keyword(s):

Ribosomal Protein ◽

Ribosomal Subunit ◽

Single Copy ◽

5S Rrna ◽

Gene Encoding ◽

Ribosomal Subunits ◽

Ribosomal Protein L1 ◽

The Stability ◽

And Function

Ribosomal protein L1 from Saccharomyces cerevisiae binds 5S rRNA and can be released from intact 60S ribosomal subunits as an L1-5S ribonucleoprotein (RNP) particle. To understand the nature of the interaction between L1 and 5S rRNA and to assess the role of L1 in ribosome assembly and function, we cloned the RPL1 gene encoding L1. We have shown that RPL1 is an essential single-copy gene. A conditional null mutant in which the only copy of RPL1 is under control of the repressible GAL1 promoter was constructed. Depletion of L1 causes instability of newly synthesized 5S rRNA in vivo. Cells depleted of L1 no longer assemble 60S ribosomal subunits, indicating that L1 is required for assembly of stable 60S ribosomal subunits but not 40S ribosomal subunits. An L1-5S RNP particle not associated with ribosomal particles was detected by coimmunoprecipitation of L1 and 5S rRNA. This pool of L1-5S RNP remained stable even upon cessation of 60S ribosomal subunit assembly by depletion of another ribosomal protein, L16. Preliminary results suggest that transcription of RPL1 is not autogenously regulated by L1.

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High RPS27A Expression Predicts Poor Prognosis in Patients With HPV Type 16 Cervical Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.752974 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qiming Wang ◽

Yan Cai ◽

Xuewen Fu ◽

Liang Chen

Keyword(s):

Cervical Cancer ◽

Poor Prognosis ◽

Biological Significance ◽

Enrichment Analysis ◽

Hpv Infection ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Protein Protein Interaction ◽

Cervical Cancer Cells ◽

Cancer Genome Atlas

In recent years, the incidence and the mortality rate of cervical cancer have been gradually increasing, becoming one of the major causes of cancer-related death in women. In particular, patients with advanced and recurrent cervical cancers present a very poor prognosis. In addition, the vast majority of cervical cancer cases are caused by human papillomavirus (HPV) infection, of which HPV16 infection is the main cause and squamous cell carcinoma is the main presenting type. In this study, we performed screening of differentially expressed genes (DEGs) based on The Cancer Genome Atlas (TCGA) database and GSE6791, constructed a protein–protein interaction (PPI) network to screen 34 hub genes, filtered to the remaining 10 genes using the CytoHubba plug-in, and used survival analysis to determine that RPS27A was most associated with the prognosis of cervical cancer patients and has prognostic and predictive value for cervical cancer. The most significant biological functions and pathways of RPS27A enrichment were subsequently investigated with gene set enrichment analysis (GSEA), and integration of TCGA and GTEx database analyses revealed that RPS27A was significantly expressed in most cancer types. In this study, our analysis revealed that RPS27A can be used as a prognostic biomarker for HPV16 cervical cancer and has biological significance for the growth of cervical cancer cells.

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