IGF signaling pathway analysis of osteosarcomas reveals the prognostic value of pAKT localization

2013 ◽  
Vol 9 (11) ◽  
pp. 1733-1740 ◽  
Author(s):  
Addy CM van de Luijtgaarden ◽  
Melissa HS Roeffen ◽  
Manon A Leus ◽  
Uta E Flucke ◽  
Bart HWB Schreuder ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pathway Analysis ◽  
Prognostic Value ◽  
Igf Signaling

scholarly journals DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guillaume B. Cardin ◽  
Monique Bernard ◽  
Francis Rodier ◽  
Apostolos Christopoulos
Keyword(s):  
Breast Carcinoma ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Colorectal Adenocarcinoma ◽  
Prostate Adenocarcinoma ◽  
Small Cell ◽  
Invasive Breast Carcinoma ◽  
Integrin Signaling ◽  
Small Cell Lung ◽  
And Function

AbstractGermline single nucleotide polymorphisms in the promoter region of the DCBLD1 gene are associated with non-smoking cases of both non-small cell lung carcinoma (NSCLC) and human papillomavirus-negative head and neck cancer. However the clinical relevance and function of DCBLD1 remain unclear. This multicenter retrospective study was designed to evaluate the prognostic value and function of DCBLD1 in the four main solid cancers: NSCLC, invasive breast carcinoma, colorectal adenocarcinoma and prostate adenocarcinoma. We included the following cohorts: GSE81089 NSCLC, METABRIC invasive breast carcinoma, GSE14333 colorectal adenocarcinoma, GSE70770 prostate adenocarcinoma and The Cancer Genome Atlas (TCGA) Firehose Legacy cohorts of all four cancers. DCBLD1 gene expression was associated with a worse overall survival in multivariate analyses for both NSCLC cohorts (TCGA: P = 0.03 and GSE81089: P = 0.04) and both invasive breast carcinoma cohorts (TCGA: P = 0.02 and METABRIC: P < 0.001). Patients with high DCBLD1 expression showed an upregulation of the integrin signaling pathway in comparison to those with low DCBLD1 expression in the TCGA NSCLC cohort (FDR = 5.16 × 10–14) and TCGA invasive breast carcinoma cohort (FDR = 1.94 × 10–05).

scholarly journals Comprehensive Analysis of SFRP Family Members Prognostic Value and Immune Infiltration in Gastric Cancer

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 522
Author(s):  
Dehua Liu ◽  
Chenyu Sun ◽  
Nahyun Kim ◽  
Chandur Bhan ◽  
John Pocholo Whitaker Tuason ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Immune Cell ◽  
System Development ◽  
Wnt Signaling Pathway ◽  
Immune System Development ◽  
Precision Therapy ◽  
Gastric Cancer Patients

Gastric cancer (GC) is the fifth most common cancer globally. Secreted frizzled-related proteins (SFRP) are important elements associated with the Wnt signaling pathway, and its dysregulated expression is found in multiple cancers. However, the function of distinct SFRPs in GC remains poorly understood. We investigated the differential expression, prognostic value, and immune cell infiltration of SFRPs in gastric cancer patients from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan–Meier plotter, cBioPortal, STRING, Gene-MANIA, DAVID, MethSurv, and TIMER databases. We found that the expression levels of SFRP2 and SFRP4 were significantly increased in GC tissues, whereas the SFRP1 and SFRP5 expressions were reduced. SFRP1, SFRP2, and SFRP5 were significantly correlated with the clinical cancer stage in GC patients. Higher expression of SFRPs was associated with short overall survival (OS) in GC patients. Besides, high SFRPs methylation showed favorable OS in GC patients. The functions of SFRPs were primarily related to the Wnt signaling pathway, immune system development, and basal cell carcinoma. The expression of SFRPs was strongly correlated with immune infiltrating cells, including CD4+ T cells and macrophages in GC. Our study indicated that SFRPs could be potential targets of precision therapy and prognostic biomarkers for the survival of GC patients.

scholarly journals Icariin promotes osteoblastic differentiation in OVX mice via MAPK signaling pathway revealed by profiling

2018 ◽  
Vol 01 (01) ◽  
pp. 33-41
Author(s):  
Qin Bian ◽  
Shufen Liu ◽  
Yongjian Zhao ◽  
Jianhua Huang ◽  
Ziyin Shen
Keyword(s):  
Bone Mass ◽  
Signaling Pathway ◽  
Pathway Analysis ◽  
Ex Vivo ◽  
Osteoblastic Differentiation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
The Self ◽  
Self Renewal ◽  
Colony Forming Unit

Objective: Icariin (ICA), an extract from epimedium, has been reported to be effective in promoting bone formation. The objective of the study is to search for the molecular targets of ICA in bone mesenchymal stem cells (bMSCs) from the mice with ovariectomy (OVX)-induced osteoporosis. Methods: Six-month-old Imprinting Control Region (ICR) mice that underwent OVX were treated with ICA. After three months, bone mass was evaluated by microcomputed tomography, morphometry and immunohistological detection. bMSCs were isolated from the femur and tibia to observe the self-renewal and differentiation capacities using colony-forming unit fibroblastic (CFU-F), colony-forming unit adipocyte (CFU-Adipo) and alkaline phosphatase (ALP) staining. In addition, microarray of bMSCs ex vivo was measured two weeks after ICA treatment and analyzed by heatmap and pathway analysis. The signaling pathway was further explored by western blot assay and inhibitors of p38 and ERK: SB203508 and PD98059. Results: [Formula: see text]CT displayed a decrease in bone mass for three months after OVX. ICA treatment increased the trabecular thickness (Tb.Th), osteoblast number while decreased osteoclast number, elevating osteocalcin (OC) protein levels in vivo and facilitating the self-renewal and osteoblastic differentiation of bMSCs ex vivo. Microarray data indicated ICA rescued several gene expressions that were dysregulated by OVX. Pathway analysis revealed that the core genes acted by ICA were highly involved in MAPK signaling pathway. Further study demonstrated ICA suppressed ERK while stimulated p38 phosphorylation to promote osteoblastic differentiation in vitro. Conclusion: ICA promotes osteoblastic differentiation of bMSCs in OVX mice. MAPK signaling pathway might be involved in the process.

scholarly journals Construction and validation of a novel prognostic signature of microRNAs in lung adenocarcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e10470
Author(s):  
Wanzhen Li ◽  
Shiqing Liu ◽  
Shihong Su ◽  
Yang Chen ◽  
Gengyun Sun
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Target Genes ◽  
Predictive Accuracy ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Tissue Samples ◽  
Gene Set ◽  
Differentially Expressed Mirnas

MicroRNA (miRNA, miR) has been reported to be highly implicated in a wide range of biological processes in lung cancer (LC), and identification of differentially expressed miRNAs between normal and LC samples has been widely used in the discovery of prognostic factors for overall survival (OS) and response to therapy. The present study was designed to develop and evaluate a miRNA-based signature with prognostic value for the OS of lung adenocarcinoma (LUAD), a common histologic subtype of LC. In brief, the miRNA expression profiles and clinicopathological factors of 499 LUAD patients were collected from The Cancer Genome Atlas (TCGA) database. Kaplan–Meier (K-M) survival analysis showed significant correlations between differentially expressed miRNAs and LUAD survival outcomes. Afterward, 1,000 resample LUAD training matrices based on the training set was applied to identify the potential prognostic miRNAs. The least absolute shrinkage and selection operator (LASSO) cox regression analysis was used to constructed a six-miRNA based prognostic signature for LUAD patients. Samples with different risk scores displayed distinct OS in K-M analysis, indicating considerable predictive accuracy of this signature in both training and validation sets. Furthermore, time-dependent receiver operating characteristic (ROC) analysis demonstrated the nomogram achieved higher predictive accuracy than any other clinical variables after incorporating the clinical information (age, sex, stage, and recurrence). In the stratification analysis, the prognostic value of this classifier in LUAD patients was validated to be independent of other clinicopathological variables, such as age, gender, tumor recurrence, and early stage. Gene set annotation analyses were also conducted through the Hallmark gene set and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, indicating target genes of the six miRNAs were positively related to various molecular pathways of cancer, such as hallmark UV response, Wnt signaling pathway and mTOR signaling pathway. In addition, fresh cancer tissue samples and matched adjacent tissue samples from 12 LUAD patients were collected to verify the expression of miR-582’s target genes in the model, further revealing the potential relationship between SOX9, RASA1, CEP55, MAP4K4 and LUAD tumorigenesis, and validating the predictive value of the model. Taken together, the present study identified a robust signature for the OS prediction of LUAD patients, which could potentially aid in the individualized selection of therapeutic approaches for LUAD patients.

scholarly journals Establishment of a Macrophage Phenotypic Switch Related Prognostic Signature in Patients With Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Mu-xing Li ◽  
Hang-yan Wang ◽  
Chun-hui Yuan ◽  
Zhao-lai Ma ◽  
Bin Jiang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Regression Analysis ◽  
Signaling Pathway ◽  
Risk Score ◽  
Prognostic Value ◽  
Risk Group ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Prognostic Signature ◽  
Phenotypic Switch

IntroductionMacrophage phenotype switch plays a vital role in the progression of malignancies. We aimed to build a prognostic signature by exploring the expression pattern of macrophage phenotypic switch related genes (MRGs) in the Cancer Genome Atlas (TCGA)—pancreatic adenocarcinoma (PAAD), Genotype-Tissue Expression (GTEx)-Pancreas, and Gene Expression Omnibus (GEO) databases.MethodsWe identified the differentially expressed genes between the PAAD and normal tissues. We used single factor Cox proportional risk regression analysis, Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and multivariate Cox proportional hazard regression analysis to establish the prognosis risk score by the MRGs. The relationships between the risk score and immune landscape, “key driver” mutations and clinicopathological factors were also analyzed. Gene-set enrichment analysis (GSEA) analysis was also performed.ResultsWe detected 198 differentially expressed MRGs. The risk score was constructed based on 9 genes (KIF23, BIN1, LAPTM4A, ERAP2, ATP8B2, FAM118A, RGS16, ELMO1, RAPGEFL1). The median overall survival time of patients in the low-risk group was significantly longer than that of patients in the high-risk group (P &lt; 0.001). The prognostic value of the risk score was validated in GSE62452 dataset. The prognostic performance of nomogram based on risk score was superior to that of TNM stage. And GSEA analysis also showed that the risk score was closely related with P53 signaling pathway, pancreatic cancer and T cell receptor signaling pathway. qRT-PCR assay showed that the expressions of the 9 MRGs in PDAC cell lines were higher than those in human pancreatic ductal epithelium cell line.ConclusionsThe nine gene risk score could be used as an independent prognostic index for PAAD patients. Further studies validating the prognostic value of the risk score are warranted.

scholarly journals Protein Expression and Prognostic Value of Genes in the erb-b Signaling Pathway in Advanced Ovarian Carcinomas

2005 ◽  
Vol 124 (3) ◽  
pp. 392-401 ◽  
Author(s):  
Yun Wang ◽  
Gunnar B. Kristensen ◽  
Åslaug Helland ◽  
Jahn M. Nesland ◽  
Anne-Lise Børresen-Dale ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Prognostic Value ◽  
Ovarian Carcinomas
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