Systematic Analysis of the Expression and Prognostic Significance of P4HA1 in Pancreatic Cancer and Construction of a lncRNA-miRNA-P4HA1 Regulatory Axis

Objectives. Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) plays a crucial role in modulating extracellular matrix component and promoting tumor progression by changing tumor adhesion, migration, and other biological behaviors in some cancers. However, its expression pattern, biological function, and underlying mechanism in pancreatic cancer remain largely unclear. Materials and Methods. In this study, a set of bioinformatics tools were used to analyze the expression of P4HA1 and its prognostic value in pancreatic cancer. In addition, the mechanism through which P4HA1 promotes the progression of pancreatic cancer was explored by constructing a competing endogenous RNA (ceRNA) regulatory axis. Results. It was found that the mRNA and protein expression of P4HA1 was significantly higher in pancreatic cancer tissues than in normal tissues. Its high P4HA1 expression correlated with poor clinicopathological features (T stage: P = 0.0078 ; N stage: P = 0.0124 ; TNM stage: P = 0.0013 ; pathological grade: P = 0.0108 ) and poor prognosis [OS: HR = 1 , 95% CI (1-1.01), P = 0.00028 ; DSS: HR = 1 , 95% CI (1-1.01), P = 0.00049 ; PFI: HR = 1.01 , 95% CI (1.01-1.02), P = 0.0057 ; and DFI: HR = 1 , 95% CI (1-1.01), P = 0.0034 ]. The LINC01503/miR-335-5p/P4HA1 axis might mediate the effects of P4HA1 in promoting the progression on pancreatic cancer. Conclusions. Collectively, our findings suggest that high expression of P4HA1 may be used as a promising prognostic biomarker and could be considered for the development of a novel therapeutic strategy for pancreatic cancer in the future.

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Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000493956 ◽

2018 ◽

Vol 50 (1) ◽

pp. 41-51 ◽

Cited By ~ 16

Author(s):

Xiangrong Cui ◽

Qin Yi ◽

Xuan Jing ◽

Yue Huang ◽

Jie Tian ◽

...

Keyword(s):

Breast Cancer ◽

Large Scale ◽

Triple Negative ◽

Methylation Status ◽

Prognostic Significance ◽

Human Breast ◽

Heat Map ◽

Systematic Analysis ◽

Normal Tissues ◽

Cancer Tissues

Background/Aims: Maternally expressed gene 3 (MEG3) is an imprinted gene with maternal expression, which may function as a tumor suppressor by inhibiting angiogenesis. To identify the prognostic value of MEG3 in breast cancer, systematic analysis was performed in this study. Methods: To evaluate gene alteration during breast carcinogenesis, we explored MEG3 expression using the Serial Analysis of Gene Expression Genie suite and Oncomine analysis. The prognostic roles of MEG3 in breast cancer were investigated using the PrognoScan database. The heat map and methylation status of MEG3 were determined using the UCSC Genome Browser. Results: We found that MEG3 was more frequently downregulated in breast cancer than in normal tissues and this correlated with prognosis. However, estrogen receptor and progesterone receptor status were found to be positively correlated with MEG3 expression. Conversely, basal-like status, triple-negative breast cancer status, and Scarff Bloom & Richardson grade criterion were negatively correlated with MEG3 expression. Following data mining in multiple big data databases, we confirmed a positive correlation between MEG3 and heparan sulfate proteoglycan 2 (HSPG2) expression in breast cancer tissues. Conclusion: MEG3 could be adopted as a marker to predict the prognosis of breast cancer with HSPG2. However, large-scale and comprehensive research is needed to clarify our results.

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CircRHOT1 Mediated Cell Proliferation, Apoptosis and Invasion of Pancreatic Cancer Cells by Sponging miR-125a-3p

10.21203/rs.3.rs-19451/v1 ◽

2020 ◽

Author(s):

Sunkai Ling ◽

Yanru He ◽

Xiaoxue Li ◽

Mingyue Hu ◽

Yu Ma ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Biological Function ◽

Diagnostic Marker ◽

Biological Functions ◽

Normal Tissues ◽

Qrt Pcr ◽

Pancreatic Cancer Cells ◽

Cancer Tissues

Abstract Background: The present study aimed to investigate the mechanistic biological function of circRHOT1 in pancreatic cancer cells.Methods: The expression of circRHOT1 and miR-125a-3p in pancreatic cancer tissues and their paired adjacent normal tissues was quantified by qRT-PCR. By knocking down or overexpressing circRHOT1 and miR-125a-3p in pancreatic cancer cells, their functions and potential mechanisms were explored.Results: circRHOT1 was overexpressed in pancreatic cancer tissues and cell lines, and it was found to directly bind to miR-125a-3p, acting as an endogenous sponge to inhibit its activity. Knockdown of circRHOT1 expression significantly inhibited proliferation as well as invasion, and it promoted apoptosis of pancreatic cancer cells via the regulation of E2F3 through the targeting of miR-125a-3p.Conclusion: Taken together, our results demonstrated that circRHOT1 plays critical roles in regulating the biological functions of pancreatic cancer cells, suggesting that circRHOT1 may serve as a potential diagnostic marker and therapeutic target for patients with pancreatic cancer.

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O11 Activated leukocyte cell adhesion molecule (ALCAM/CD166) is an important clinical and prognostic indicator in pancreatic cancer

British Journal of Surgery ◽

10.1093/bjs/znab282.016 ◽

2021 ◽

Vol 108 (Supplement_5) ◽

Author(s):

Y M Yang ◽

A J Sanders ◽

X Dong ◽

Y Cui ◽

C Hao ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Adhesion ◽

Adhesion Molecule ◽

Cell Adhesion Molecule ◽

Prognostic Indicator ◽

Tnm Staging ◽

Normal Tissues ◽

Heterotypic Interactions ◽

A Cell ◽

Cancer Tissues

Abstract Introduction Activated leukocyte cell adhesion molecule (ALCAM/CD166) is a cell adhesion molecule and one of the potential metastasis ‘soil’ receptors that via homotypic and heterotypic interactions, mediates cell adhesion. The present study investigated the clinical, pathological and prognostic value of ALCAM in patients with pancreatic cancer. Method Pancreatic cancer tissues (n = 223), collected immediately after surgery, were analysed for levels of the ALCAM transcripts. The expression was analysed against clinical, pathological and clinical outcome of the patients. We validated our findings with an available TCGA database (n = 117), including correlations with the ALCAM interactive partners. Result Pancreatic cancer tissues had significantly higher levels of ALCAM transcript than normal tissues (P < 0.00001). There were no significant differences with staging, differentiation and tumour locations. Tumours from patients who died of pancreatic cancer had significantly high levels of ALCAM compared with those who lived (P = 0.018), finding also supported by ROC analysis (P = 0.016). Multivariant analysis showed ALCAM as an independent prognosis factor for overall survival (hazardous ratio 5.485), with both nodal status and TNM staging contributing to the model (HR 2.578 and 3.02 respectively). A surprising finding was the relationship between ALCAM expression and microvessel embolism of tumour cells (P = 0.021, with vs without tumour embolism). ALCAM significantly correlated with its interactive protein partners including CD6 and ITGB1, but not L1CAM. Conclusion ALCAM/CD166 expression is aberrant in pancreatic cancer and the raised expression is an independent prognostic factor for the survival of the patients and the microvessel embolism by cancer cells. Take-home Message ALCAM is a prognostic indicator for survival and tumour embolism in pancreatic cancer

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High Expression of AMIGO2 Is an Independent Predictor of Poor Prognosis in Pancreatic Cancer

10.21203/rs.3.rs-557347/v1 ◽

2021 ◽

Author(s):

zhang jing ◽

Fu xi feng

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Tp53 Mutation ◽

Enrichment Analysis ◽

High Expression ◽

Normal Tissues ◽

Kaplan Meier ◽

Human Protein Atlas ◽

Cancer Tissues ◽

Kaplan Meier Plotter

Abstract Background.The AMIGO2 extracellular domain has a leucine - rich repetitive domain (LRR) and encodes a type 1 transmembrane protein , and is a member of the AMIGO gene family .Although the abnormal expression of AMIGO2 is associated with multiple tumors , the relationship with pancreatic cancer is not clear .Methods.The expression of AMIGO2 mRNA and proteins in pancreatic cancer was analyzed using NCBI GEO database and GEPIA2、Human Protein Atlas database.The RNA sequencing data of pancreatic cancer and clinical data of pancreatic cancer patients in TCGA public database were retrospectively analyzed. AMIGO2 gene expression data and their corresponding clinical information in the sample were analyzed retrospectively. The diagnostic value of AMIGO2 expression in pancreatic cancer patients was determined by receiver operating characteristic (ROC) curve analysis. The effects of AMIGO2 expression differences on survival time of pancreatic cancer patients were analyzed by Kaplan-Meier Plotter database and GEPIA2 database.The correlation between AMIGO2 gene and TP53 mutation in pancreatic cancer was analyzed by UALCAN database and TIMER database. The similar genes of AMIGO2 in pancreatic cancer were analyzed by GEPIA2 database, and the biological behavior, cellular composition, molecular function enrichment analysis and protein interaction of similar genes were analyzed by DAVID database and Metascape database. enrichment analysis of AMIGO2 similar gene pathways using KEGG database. The MSIGDB cancer coexpression module in Harmonizome database and TIMER database were used to study the gene coexpression of AMIGO2 in pancreatic cancer. AMIGO2 transcription factors were predicted using the JASPER database. The pathway of AMIGO2 transcription factors and co-expression genes was studied by KEGG database.Results. The expression of AMIGO2 (GSE16515, GSE15471) in pancreatic cancer tissues was significantly higher than that in normal tissues (P < 0.05). The GEPIA2 database also confirmed that the expression of AMIGO2 in pancreatic cancer tissues was significantly higher than that in normal tissues. The expression level of AMIGO2 gene was correlated with lymph node metastasis and histological grade of pancreatic cancer (P<0.05). The high expression of AMIGO2 protein in pancreatic cancer was confirmed in Human Protein Atlas database. The overall survival rate and progression-free survival rate of pancreatic cancer patients with high expression of AMIGO2 were significantly shorter than those of patients with low expression of AMIGO2 in Kaplan-Meier Plotter database and GEPIA2 database. In the gene ontology analysis, it is found that AMIGO2 is involved in cell adhesion, proliferation, migration, apoptosis and other biological processes. KEGG analysis pathway is concentrated in the focal adhesion pathway, mitotic cell cycle changes, and the regulation of cell protein localization. Abnormal expression of AMIGO2 was found in pancreatic cancer caused by TP53 mutation in UALCAN and TIMER databases.In JASPAR database, we predicted that there are 10 transcription sites between AMIGO2 and transcription factor MYB. In addition, there are positive genes related to AMIGO2 in TIMER database and transcription factor MYB regulates tumor cell proliferation and apoptosis in PI3K-Akt signal transduction pathway and WNT signal pathway in pancreatic cancer.

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Overexpression of ANP32E is associated with poor prognosis of pancreatic cancer and promotes cell proliferation and migration through regulating β-catenin

10.21203/rs.3.rs-27702/v1 ◽

2020 ◽

Author(s):

Jianwei Zhang ◽

Zhongmin Lan ◽

Guotong Qiu ◽

Hu Ren ◽

Yajie Zhao ◽

...

Keyword(s):

Cell Cycle ◽

Pancreatic Cancer ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Colony Growth ◽

Normal Tissues ◽

Cell Proliferation And Migration ◽

And Migration ◽

Cancer Tissues ◽

Proliferation And Migration

Abstract Background: Pancreatic cancer is a malignant tumor with high lethality. Acidic nuclear phosphoprotein 32 family member E (ANP32E) is a specific H2A.Z chaperone. The role of ANP32E in pancreatic cancer is poorly understood. This study aimed to investigate the clinical relevance and function of ANP32E in pancreatic cancer.Methods: The expression of ANP32E in 179 pancreatic cancer tissues and 171 normal tissues, and its correlation with patients’ survival were analyzed from the TCGA database. ANP32E was overexpressed and silenced using lentivirus. siRNA was used to knock down β-catenin. CCK8, colony formation, cell cycle detection and Transwell assays were performed to determine cell proliferation and migration. qRT-PCR and Western blot were conducted to detect mRNA and protein expression.Results: ANP32E was an oncogene in pancreatic cancer. ANP32E was up-regulated in pancreatic cancer tissues and cells. Up-regulation of ANP32E predicted poor survival in patients. Lentivirus-mediated knockdown of ANP32E suppressed the proliferation, colony growth and migration of PANC1 and MIA cells. By contrast, ANP32E overexpression promoted the proliferation and migration capacity of the cells. In addition, ANP32E overexpression accelerated the cell cycle progression in PANC1 and MIA cells. Molecular experiments showed that ANP32E activated β-catenin/cyclin D1 signaling. Silencing of β-catenin reduced cell proliferation and migration in ANP32E over-expressed cells.Conclusion: Our results reveal that ANP32E functions as an oncogene in pancreatic cancer via activating β-catenin.

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Expression and Prognostic Significance of lncRNA MALAT1 in Pancreatic Cancer Tissues

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2014.15.7.2971 ◽

2014 ◽

Vol 15 (7) ◽

pp. 2971-2977 ◽

Cited By ~ 76

Author(s):

Jiang-Hua Liu ◽

Gang Chen ◽

Yi-Wu Dang ◽

Chun-Jun Li ◽

Dian-Zhong Luo

Keyword(s):

Pancreatic Cancer ◽

Prognostic Significance ◽

Lncrna Malat1 ◽

Cancer Tissues

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Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer

Current Medicinal Chemistry ◽

10.2174/0929867324666170206142658 ◽

2017 ◽

Vol 24 (13) ◽

Cited By ~ 50

Author(s):

Safieh Ebrahimi ◽

Mina Hosseini ◽

Soodabeh Shahidsales ◽

Mina Maftouh ◽

Gordon A. Ferns ◽

...

Keyword(s):

Pancreatic Cancer ◽

Signaling Pathway ◽

Therapeutic Strategy ◽

Pi3k Signaling ◽

Pi3k Signaling Pathway

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Prognostic significance of bone marrow FDG uptake in patients with gynecological cancer

Scientific Reports ◽

10.1038/s41598-021-81298-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kotaro Shimura ◽

Seiji Mabuchi ◽

Naoko Komura ◽

Eriko Yokoi ◽

Katsumi Kozasa ◽

...

Keyword(s):

Ovarian Cancer ◽

Bone Marrow ◽

Poor Prognosis ◽

Gynecological Cancer ◽

Prognostic Significance ◽

Standardized Uptake Value ◽

Suppressor Cells ◽

Underlying Mechanism ◽

Fdg Uptake

AbstractWe investigated the prognostic significance and the underlying mechanism of increased bone marrow (BM) 2-(18F) fluoro-2-deoxy-D-glucose as a tracer (FDG)-uptake in patients with gynecological cancer. A list of patients diagnosed with cervical, endometrial, and ovarian cancer from January 2008 to December 2014 were identified. Then, through chart reviews, 559 patients who underwent staging by FDG-positron emission tomography (PET)/computed tomography (CT) and subsequent surgical resection were identified, and their clinical data were reviewed retrospectively. BM FDG-uptake was evaluated using maximum standardized uptake value (SUVmax) and BM-to-aorta uptake ratio (BAR). As a result, we have found that increased BAR was observed in 20 (8.7%), 21 (13.0%), 21 (12.6%) of cervical, endometrial, and ovarian cancer, respectively, and was associated with significantly shorter survival. Increased BAR was also closely associated with increased granulopoiesis. In vitro and in vivo experiments revealed that tumor-derived granulocyte colony-stimulating factor (G-CSF) was involved in the underlying causative mechanism of increased BM FDG-uptake, and that immune suppression mediated by G-CSF-induced myeloid-derived suppressor cells (MDSCs) is responsible for the poor prognosis of this type of cancer. In conclusion, increased BM FDG-uptake, as represented by increased BAR, is an indicator of poor prognosis in patients with gynecological cancer.

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Evaluation of the prognostic value of CBXs in gastric cancer patients

Scientific Reports ◽

10.1038/s41598-021-91649-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mengya He ◽

Limin Yue ◽

Haiyan Wang ◽

Feiyan Yu ◽

Mingyang Yu ◽

...

Keyword(s):

Gastric Cancer ◽

Target Genes ◽

Prognostic Significance ◽

Disease Free Survival ◽

Genetic Alterations ◽

Genetic Mutation ◽

The Cancer Genome Atlas ◽

Normal Tissues ◽

Interactive Analysis ◽

Gastric Cancer Patients

AbstractChromobox (CBX) proteins were suggested to exert epigenetic regulatory and transcriptionally repressing effects on target genes and might play key roles in the carcinogenesis of a variety of carcinomas. Nevertheless, the functions and prognostic significance of CBXs in gastric cancer (GC) remain unclear. The current study investigated the roles of CBXs in the prognosis of GC using the Oncomine, The Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, The Cancer Genome Atlas (TCGA), and cBioPortal databases. CBX1/2/3/4/5 were significantly upregulated in GC tissues compared with normal tissues, and CBX7 was downregulated. Multivariate analysis showed that high mRNA expression levels of CBX3/8 were independent prognostic factors for prolonged OS in GC patients. In addition, the genetic mutation rate of CBXs was 37% in GC patients, and genetic alterations in CBXs showed no association with OS or disease-free survival (DFS) in GC patients. These results indicated that CBX3/8 can be prognostic biomarkers for the survival of GC patients.

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Anti–Na+/K+-ATPase immunotherapy ameliorates α-synuclein pathology through activation of Na+/K+-ATPase α1–dependent autophagy

Science Advances ◽

10.1126/sciadv.abc5062 ◽

2021 ◽

Vol 7 (5) ◽

pp. eabc5062

Author(s):

Lei Cao ◽

Siping Xiong ◽

Zhiyuan Wu ◽

Lei Ding ◽

Yebo Zhou ◽

...

Keyword(s):

Monoclonal Antibody ◽

Tyrosine Hydroxylase ◽

Neurodegenerative Diseases ◽

Motor Function ◽

Therapeutic Strategy ◽

Underlying Mechanism ◽

Behavioral Tests ◽

Behavioral Deficits ◽

Cellular Homeostasis ◽

Beneficial Effects

Na+/K+-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson’s disease (PD). Here, we report that reduction of NKA activity in NKAα1+/− mice aggravates α-synuclein–induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein–induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.

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