scholarly journals Integrated analysis of mRNA and protein expression profiling in tubal endometriosis

Reproduction ◽  
2020 ◽  
Vol 159 (5) ◽  
pp. 601-614 ◽  
Author(s):  
Hang Qi ◽  
Huiyu Zhang ◽  
Xiaoya Zhao ◽  
Ya Qin ◽  
Guiling Liang ◽  
...  

Tubal endometriosis (tubal EM) is a subtype of endometriosis (EM) associated with fallopian tube impairments and infertility. Since the molecular mechanism underlying tubal EM is not clear, we assume that an aberrant transcriptome of fallopian tube epithelium and microenvironment changes caused by cytokines in tubal fluid are possible causes. The aim of this study was to identify potential hub mRNAs/proteins of tubal EM through integrated transcriptomic and proteomic analyses and to elucidate significant pathways, cellular functions, and interaction networks during the initiation and progression of tubal EM. We obtained human fallopian tube epithelium and tubal fluid samples from patients with and without tubal EM. Tubal epithelia were analyzed using microarray, and tubal fluid was analyzed using quantitative label-free LC-MS/MS. We identified differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) and determined common mRNAs/protein. We observed 35 commonly deregulated mRNAs/proteins, and IPA indicated that cellular movement, inflammatory response, and immune cell trafficking were significantly activated during the pathogenesis of tubal EM. We also identified acute phase response signaling pathway activation as a unique pathogenesis signature of tubal EM. Our results demonstrate that an integrated analysis of the transcriptome and proteome has the potential to reveal novel disease mechanisms at a molecular level.

2009 ◽  
Vol 303 (1-2) ◽  
pp. 7-12 ◽  
Author(s):  
A.P. Hess ◽  
D.M. Baston-Buest ◽  
A. Schanz ◽  
J. Hirchenhain ◽  
P. Bielfeld ◽  
...  

2019 ◽  
Vol 199 ◽  
pp. 1-14 ◽  
Author(s):  
Talita Helen Bombardelli Gomig ◽  
Iglenir João Cavalli ◽  
Ricardo Lehtonen Rodrigues de Souza ◽  
Evelyn Vieira ◽  
Aline Castro Rodrigues Lucena ◽  
...  

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii4-ii4
Author(s):  
Liang-Bo Wang ◽  
Alla Karpova ◽  
Marina Gritsenko ◽  
Jennifer Kyle ◽  
Song Cao ◽  
...  

Abstract Glioblastoma (GBM) is the most aggressive nervous system cancer, with median survival under 2 years. Understanding its molecular pathogenesis is crucial for improving diagnosis and treatment. We performed an integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs. We identified key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation as well as potential targets for EGFR-, TP53- and RB1-altered tumors. We detected immune subtypes, driven by the presence of distinct immune cell populations using bulk omics, validated by single nulcei RNA sequencing (snRNA-seq), and they were correlated with specific expression and histone acetylation patterns. Acetylation of histone H2B in classical-like and immune-low GBM was driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identified specific lipid distributions across subtypes and distinct global metabolic changes in IDH mutated tumors. This work highlights biological relationships which could potentially aid GBM patient stratifications for more effective treatments.


2020 ◽  
Author(s):  
Feng Jiang ◽  
Fan Zhang ◽  
Jian Chen ◽  
Junjun Wang ◽  
Lijuan Hu ◽  
...  

Abstract Background We aim to develop core modules related to pancreatic cancer (PC) to predict the prognosis of PC patients and explore their tumor microenvironment. Method: We merged 175 pancreatic cancer samples in the TCGA database with gene mutation expression, methylation level distribution, mRNA expression and pancreatic cancer-related genes into a public database, and then through weighted correlation network analysis (WGCNA), Two expression modules associated with pancreatic cancer are combined. Then, by integrating these selected genes identified from the first 10 genes of the two co-expression modules, a model risk score is established, and patients are divided into high-risk and low-risk subgroups. Kaplan-Meier survival analysis method is used to analyze differences, analyze the correlation of survival between subgroups, and analyze prognostic models. These selected core genes can divide early pancreatic cancer into two subgroups, compare the prognosis of these two groups, and screen for differentially expressed genes. Use GO and KEGG enrichment analysis to predict the function of differentially expressed genes. The differential expression level and immune cell infiltration level of these selected core genes were further analysis. Results Our findings shown nine core genes (MST1R, TMPRSS4, PTK6, KLF5, CGN, ABHD17C, MUC1, CAPN8, B3GNT3) were prognostic biomarkers of pancreatic cancer. These 9 genes could divide early pancreatic cancer into two subgroups, and the two subgroups had significant differences in prognosis, and were mainly different in functions such as digestion and extracellular cell adhesion. Further analysis revealed that the expression of these 9 genes were expressed at high levels in pancreatic cancer tissues. In addition, we validated pancreatic cancer cells and pancreatic epithelial cells through quantitative real-time PCR (qRT-PCR), suggesting that the MST1R, PTK6, ABHD17C and CGN expressed higher in PC cells. CIBERSORT analysis indicated that these genes expression were closely correlated with B-cell naive, CD8+ T cells, Macrophages M0 cells, suggesting that these genes may play a carcinogenic role in the preservation of immune-dominant status for tumor microenvironment. Conclusions Our research identified 9 key genes which may enhance our understanding of the molecular mechanisms associated with pancreatic cancer.


Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1198
Author(s):  
Marta Sikora ◽  
Ewa Bretes ◽  
Joanna Perła-Kaján ◽  
Izabela Lewandowska ◽  
Łukasz Marczak ◽  
...  

High-density lipoprotein (HDL), in addition to promoting reverse cholesterol transport, possesses anti-inflammatory, antioxidative, and antithrombotic activities. Paraoxonase 1 (PON1), carried on HDL in the blood, can contribute to these antiatherogenic activities. The PON1-Q192R polymorphism involves a change from glutamine (Q variant) to arginine (R variant) at position 192 of the PON1 protein and affects its enzymatic activity. The molecular basis of PON1 association with cardiovascular and neurological diseases is not fully understood. To get insight into the function of PON1 in human disease, we examined how genetic attenuation of PON1 levels/activity affect plasma proteomes of mice and humans. Healthy participants (48.9 years old, 50% women) were randomly recruited from the Poznań population. Four-month-old Pon1−/− (n = 17) and Pon1+/+ (n = 8) mice (50% female) were used in these experiments. Plasma proteomes were analyzed using label-free mass spectrometry. Bioinformatics analysis was carried out using the Ingenuity Pathway Analysis (IPA) resources. PON1-Q192R polymorphism and Pon1−/− genotype induced similar changes in plasma proteomes of humans and mice, respectively. The top molecular network, identified by IPA, affected by these changes involved proteins participating in lipoprotein metabolism. Other PON1 genotype-dependent proteomic changes affect different biological networks in humans and mice: “cardiovascular, neurological disease, organismal injury/abnormalities” in PON1-192QQ humans and “humoral immune response, inflammatory response, protein synthesis” and “cell-to-cell signaling/interaction, hematological system development/function, immune cell trafficking” in Pon1−/− mice. Our findings suggest that PON1 interacts with molecular pathways involved in lipoprotein metabolism, acute/inflammatory response, and complement/blood coagulation that are essential for blood homeostasis. Modulation of those interactions by the PON1 genotype can account for its association with cardiovascular and neurological diseases.


1969 ◽  
Vol 61 (1_Suppl) ◽  
pp. S80 ◽  
Author(s):  
Hubertus A. van Leusden

2018 ◽  
Vol 25 (36) ◽  
pp. 4758-4784 ◽  
Author(s):  
Amy L. Wilson ◽  
Magdalena Plebanski ◽  
Andrew N. Stephens

Cancer is one of the leading causes of death worldwide, and current research has focused on the discovery of novel approaches to effectively treat this disease. Recently, a considerable number of clinical trials have demonstrated the success of immunomodulatory therapies for the treatment of cancer. Monoclonal antibodies can target components of the immune system to either i) agonise co-stimulatory molecules, such as CD137, OX40 and CD40; or ii) inhibit immune checkpoints, such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and its corresponding ligand PD-L1. Although tumour regression is the outcome for some patients following immunotherapy, many patients still do not respond. Furthermore, chemotherapy has been the standard of care for most cancers, but the immunomodulatory capacity of these drugs has only recently been uncovered. The ability of chemotherapy to modulate the immune system through a variety of mechanisms, including immunogenic cell death (ICD), increased antigen presentation and depletion of regulatory immune cells, highlights the potential for synergism between conventional chemotherapy and novel immunotherapy. In addition, recent pre-clinical trials indicate dipeptidyl peptidase (DPP) enzyme inhibition, an enzyme that can regulate immune cell trafficking to the tumour microenvironment, as a novel cancer therapy. The present review focuses on the current immunological approaches for the treatment of cancer, and summarizes clinical trials in the field of immunotherapy as a single treatment and in combination with chemotherapy.


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