scholarly journals SUN-119 Identification of Novel Mirnas Found to Be Differentially Expressed Between ATA Risk Stratification Groups in Papillary Thyroid Carcinoma

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Luisa Fernanda Olaya A ◽  
Joanne Malek ◽  
Brodie Hookins ◽  
Tripti Joshi ◽  
Watson Zara ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Cancer Progression ◽  
Normal Tissue ◽  
Disease Recurrence ◽  
Differentially Expressed ◽  
Roc Curve Analysis ◽  
Intermediate Group ◽  
Qrt Pcr ◽  
Tiered System ◽  
Risk Of Disease

Abstract The study of miRNAs in PTC has shown that these molecules can help in the diagnosis, prognosis and also as therapeutic candidates [1]. miRNAs are known to be differentially expressed in PTC compared to non-cancerous tissue and a few studies have shown association with some clinico-pathological features. However, little is known regarding their expression in relation to risk of disease progression. In this study, we examined the expression of miRNAs in patients diagnosed with PTC in association with risk of disease recurrence and/or persistence. Patients were classified by three endocrinologists to either high (H) or low (L) risk according to ATA Risk Stratification. PTC tissue was micro-dissected from Formalin Fixed Paraffin Embedded (FFPE) tissue for analysis. OPenArray analysis showed that 21 miRNAs were differentially expressed in H-L groups (n=4/grp). qRT-PCR was used to confirm these differences in a larger cohort of PTC (H=46; L=58). This comparison also included comparisons between cancer and normal tissue and investigation of miRNAs known to be differentially expressed (i.e miRNAs 222, 221 and 146b). All analysis was performed in Rstudio using ΔΔCt relative to expression of miR-16 which was not altered by PTC. By qRT-PCR, only 3 of the 21 miRNAs identified by OpenArray analysis, were differentially expressed in H vs L risk (each P<0.05). These miRNAs are known to be involved in cancer progression pathways but have not been reported in PTC. Individual Receiver Operating Characteristic (ROC) curve analysis of these 3 miRNAs had AUC as follows (miR 1: 0.62, miR 2: 0.62, miR 3: 0.64,) and when analyzed together, the AUC model was improved (AUC=0.76). Examination of cancer vs normal tissue confirmed higher expression miR-146b, miR-221 and miR-222 (each P<0.05). However, these miRNAs were not differentially expressed when H vs L risk were analysed. In this study, we identified 3 miRNAs with potential utility for the stratification of patients into those with H or L risk disease recurrence/persistence. As the current ATA 3-tiered system used is still a reflection of the continuum of risk that patients have, whether these 3 miRNAs may have the utility to further stratify those in the intermediate group remains to be investigated. Reference: 1. Ramírez-Moya, J. and P. Santisteban, miRNA-Directed Regulation of the Main Signaling Pathways in Thyroid Cancer. Frontiers in Endocrinology, 2019. 10: p. 430.

Using PSMA (prostate-specific membrane antigen) evaluation on prostate biopsies for risk stratification at time of initial diagnosis.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 6-6 ◽  
Author(s):  
Marie C. Hupe ◽  
Christian Philippi ◽  
Doris Roth ◽  
Christiane Kuempers ◽  
Julika Ribbat-Idel ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Treatment Decision ◽  
Disease Recurrence ◽  
Initial Diagnosis ◽  
Curative Surgery ◽  
Grade Group ◽  
Prostate Biopsies ◽  
Increased Risk ◽  
Risk Of Disease ◽  
Psma Expression

6 Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis for individual treatment decision is still a major clinical challenge. PSMA expression has emerged as a promising prognostic biomarker since its overexpression in radical prostatectomy specimens (RP) has been linked to disease recurrence. Aim of our study was to assess the prognostic value of PSMA on prostate biopsies (Bx) thus improving risk stratification at time of initial diagnosis. Methods: Immunohistochemistry for PSMA expression was performed on 294 Bx with corresponding RP, 621 primary tumor foci from 242 RP, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases, and 52 benign prostatic samples. Grade group, PSA, TNM-, and R-status were assessed as clinico-pathologic features. Primary endpoint was recurrence-free survival (RFS). Chi-square, ANOVA-analyses, Cox regression and log rank tests were performed for statistical analyses. Results: PSMA expression significantly associates with grade group and initial PSA level. Elevated PSMA expression on both RP and Bx significantly correlates with an increased risk of disease recurrence after curative surgery. 5-year RFS rates are 88.2%, 74.2%, 67.7%, and 26.8% for patients with no, low, medium, or high PSMA expression on Bx, respectively. Elevated PSMA level on Bx predict a 4-fold increased risk of disease recurrence independently from initial PSA and grade group on Bx. PSMA expression significantly increases during PCa progression. Conclusions: PSMA qualifies as an independent prognostic biomarker on Bx at time of initial diagnosis in addition to the established markers PSA and grade group. PSMA predicts disease recurrence following curative surgery and potentially improves the discrimination indolent vs. aggressive disease. We propose the routine assessment of PSMA expression on Bx for outcome prediction and risk stratification at time of initial diagnosis prior to treatment decision.

scholarly journals STAT3 regulated ARF expression suppresses prostate cancer metastasis

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Jan Pencik ◽  
Michaela Schlederer ◽  
Wolfgang Gruber ◽  
Christine Unger ◽  
Steven M. Walker ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Prognostic Markers ◽  
Disease Recurrence ◽  
Therapeutic Benefit ◽  
Increased Risk ◽  
Prostate Cancer Metastasis ◽  
Risk Of Disease ◽  
Stat3 Signalling

Abstract Prostate cancer (PCa) is the most prevalent cancer in men. Hyperactive STAT3 is thought to be oncogenic in PCa. However, targeting of the IL-6/STAT3 axis in PCa patients has failed to provide therapeutic benefit. Here we show that genetic inactivation of Stat3 or IL-6 signalling in a Pten-deficient PCa mouse model accelerates cancer progression leading to metastasis. Mechanistically, we identify p19ARF as a direct Stat3 target. Loss of Stat3 signalling disrupts the ARF–Mdm2–p53 tumour suppressor axis bypassing senescence. Strikingly, we also identify STAT3 and CDKN2A mutations in primary human PCa. STAT3 and CDKN2A deletions co-occurred with high frequency in PCa metastases. In accordance, loss of STAT3 and p14ARF expression in patient tumours correlates with increased risk of disease recurrence and metastatic PCa. Thus, STAT3 and ARF may be prognostic markers to stratify high from low risk PCa patients. Our findings challenge the current discussion on therapeutic benefit or risk of IL-6/STAT3 inhibition.

scholarly journals Several miRNAs derived from serum extracellular vesicles are potential biomarkers for early diagnosis and progression of Parkinson’s disease

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Shulei He ◽  
Lu Huang ◽  
Ci Shao ◽  
Tiejian Nie ◽  
Li Xia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Unmet Need ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Qrt Pcr

Abstract Background Blood-based test for predicting disease progression and early diagnosis of Parkinson’s disease (PD) is an unmet need in the clinic. The profiles of microRNAs (miRNAs) are regarded as potential diagnostic biomarkers for human diseases, whereas miRNAs in the periphery are susceptible to the influence of various components. MiRNAs enriched in serum extracellular vesicles (EVs) have demonstrated disease-specific advantages in diagnosis due to their high abundance, stability and resistance to degradation. This study was aimed to screen differentially expressed EV-derived miRNAs between healthy controls and PD patients to aid in diagnosis of PD. Methods A total of 31 healthy controls and 72 patients with a diagnosis of PD at different Hoehn and Yahr stages in Tangdu Hospital were included. In total, 185 differentially expressed miRNAs were obtained through RNA sequencing of serum EVs as well as edgeR and t-test analyses. Subsequently, the weighted gene co-expression network analysis (WGCNA) was utilized to identify the commonly expressed miRNAs in all stages of PD by constructing connections between modules, and specifically expressed miRNAs in each stage of PD by functional enrichment analysis. After aligning these miRNAs with PD-related miRNAs in Human miRNA Disease Database, the screened miRNAs were further validated by receiver operating characteristic (ROC) curves and quantitative real-time polymerase chain reaction (qRT-PCR) using peripheral blood EVs from 40 more participants. Results WGCNA showed that 4 miRNAs were commonly associated with all stages of PD and 13 miRNAs were specifically associated with different stages of PD. Of the 17 obtained miRNAs, 7 were validated by ROC curve analysis and 7 were verified in 40 more participants by qRT-PCR. Six miRNAs were verified by both methods, which included 2 miRNAs that were commonly expressed in all stages of PD and 4 miRNAs that were specifically expressed in different stages of PD. Conclusions The 6 serum EV-derived miRNAs, hsa-miR-374a-5p, hsa-miR-374b-5p, hsa-miR-199a-3p, hsa-miR-28-5p, hsa-miR-22-5p and hsa-miR-151a-5p, may potentially be used as biomarkers for PD progression and for early diagnosis of PD in populations.

scholarly journals Comparative transcriptomic and metabolomic analyses of carotenoid biosynthesis reveal the basis of white petal color in Brassica napus

Planta ◽  
2021 ◽  
Vol 253 (1) ◽  
Author(s):  
Ledong Jia ◽  
Junsheng Wang ◽  
Rui Wang ◽  
Mouzheng Duan ◽  
Cailin Qiao ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Molecular Mechanisms ◽  
Flower Color ◽  
Carotenoid Biosynthesis ◽  
Differentially Expressed ◽  
Transcriptome Data ◽  
Oilseed Crops ◽  
Qrt Pcr ◽  
Carotenoid Metabolism ◽  
Rapeseed Cultivar

Abstract Main conclusion The molecular mechanism underlying white petal color in Brassica napus was revealed by transcriptomic and metabolomic analyses. Abstract Rapeseed (Brassica napus L.) is one of the most important oilseed crops worldwide, but the mechanisms underlying flower color in this crop are known less. Here, we performed metabolomic and transcriptomic analyses of the yellow-flowered rapeseed cultivar ‘Zhongshuang 11’ (ZS11) and the white-flowered inbred line ‘White Petal’ (WP). The total carotenoid contents were 1.778-fold and 1.969-fold higher in ZS11 vs. WP petals at stages S2 and S4, respectively. Our findings suggest that white petal color in WP flowers is primarily due to decreased lutein and zeaxanthin contents. Transcriptome analysis revealed 10,116 differentially expressed genes with a fourfold or greater change in expression (P-value less than 0.001) in WP vs. ZS11 petals, including 1,209 genes that were differentially expressed at four different stages and 20 genes in the carotenoid metabolism pathway. BnNCED4b, encoding a protein involved in carotenoid degradation, was expressed at abnormally high levels in WP petals, suggesting it might play a key role in white petal formation. The results of qRT-PCR were consistent with the transcriptome data. The results of this study provide important insights into the molecular mechanisms of the carotenoid metabolic pathway in rapeseed petals, and the candidate genes identified in this study provide a resource for the creation of new B. napus germplasms with different petal colors.

scholarly journals Receptor Tyrosine Kinases: Role in Cancer Progression

2006 ◽  
Vol 13 (5) ◽  
pp. 191-193
Author(s):  
V. Sangwan ◽  
M. Park
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cancer Progression ◽  
Tyrosine Kinases ◽  
Normal Tissue ◽  
Receptor Tyrosine Kinases ◽  
Tight Control ◽  
Tissue Patterning

Tight control of cell proliferation and morphogenesis in conjunction with programmed cell death (apoptosis) is required to ensure normal tissue patterning. [...]

scholarly journals Microarray analysis reveals an inflammatory transcriptomic signature in peripheral blood for sciatica

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yi Wang ◽  
Guogang Dai ◽  
Ling Jiang ◽  
Shichuan Liao ◽  
Jiao Xia
Keyword(s):  
Functional Analysis ◽  
Network Analysis ◽  
Peripheral Blood ◽  
Differentially Expressed ◽  
Healthy Controls ◽  
Toll Like Receptor ◽  
Qrt Pcr ◽  
Transcriptomic Signature ◽  
Transcriptional Changes ◽  
Key Genes

Abstract Background Although the pathology of sciatica has been studied extensively, the transcriptional changes in the peripheral blood caused by sciatica have not been characterized. This study aimed to characterize the peripheral blood transcriptomic signature for sciatica. Methods We used a microarray to identify differentially expressed genes in the peripheral blood of patients with sciatica compared with that of healthy controls, performed a functional analysis to reveal the peripheral blood transcriptomic signature for sciatica, and conducted a network analysis to identify key genes that contribute to the observed transcriptional changes. The expression levels of these key genes were assessed by qRT-PCR. Results We found that 153 genes were differentially expressed in the peripheral blood of patients with sciatica compared with that of healthy controls, and 131 and 22 of these were upregulated and downregulated, respectively. A functional analysis revealed that these differentially expressed genes (DEGs) were strongly enriched for the inflammatory response or immunity. The network analysis revealed that a group of genes, most of which are related to the inflammatory response, played a key role in the dysregulation of these DEGs. These key genes are Toll-like receptor 4, matrix metallopeptidase 9, myeloperoxidase, cathelicidin antimicrobial peptide, resistin and Toll-like receptor 5, and a qRT-PCR analysis validated the higher transcript levels of these key genes in the peripheral blood of patients with sciatica than in that of healthy controls. Conclusion We revealed inflammatory characteristics that serve as a peripheral blood transcriptomic signature for sciatica and identified genes that are essential for mRNA dysregulation in the peripheral blood of patients with sciatica.

scholarly journals ITRAQ-based quantitative proteomic analysis of Fusarium moniliforme (Fusarium verticillioides) in response to Phloridzin inducers

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Rong Zhang ◽  
Weitao Jiang ◽  
Xin Liu ◽  
Yanan Duan ◽  
Li Xiang ◽  
...  
Keyword(s):  
Fusarium Moniliforme ◽  
Abiotic Factors ◽  
Fusarium Verticillioides ◽  
Protein Profile ◽  
Sugar Metabolism ◽  
Differentially Expressed ◽  
Pcr Analysis ◽  
Differentially Expressed Proteins ◽  
Apple Replant Disease ◽  
Qrt Pcr

Abstract Background Apple replant disease (ARD) has been reported from all major fruit-growing regions of the world, and is often caused by biotic factors (pathogen fungi) and abiotic factors (phenolic compounds). In order to clarify the proteomic differences of Fusarium moniliforme under the action of phloridzin, and to explore the potential mechanism of F. moniliforme as the pathogen of ARD, the role of Fusarium spp. in ARD was further clarified. Methods In this paper, the quantitative proteomics method iTRAQ analysis technology was used to analyze the proteomic differences of F. moniliforme before and after phloridzin treatment. The differentially expressed protein was validated by qRT-PCR analysis. Results A total of 4535 proteins were detected, and 293 proteins were found with more than 1.2 times (P< 0.05) differences. In-depth data analysis revealed that 59 proteins were found with more than 1.5 times (P< 0.05) differences, and most proteins were consistent with the result of qRT-PCR. Differentially expressed proteins were influenced a variety of cellular processes, particularly metabolic processes. Among these metabolic pathways, a total of 8 significantly enriched KEGG pathways were identified with at least 2 affiliated proteins with different abundance in conidia and mycelium. Functional pathway analysis indicated that up-regulated proteins were mainly distributed in amino sugar, nucleotide sugar metabolism, glycolysis/ gluconeogenesis and phagosome pathways. Conclusions This study is the first to perform quantitative proteomic investigation by iTRAQ labeling and LC-MS/MS to identify differentially expressed proteins in F. moniliforme under phloridzin conditions. The results confirmed that F. moniliforme presented a unique protein profile that indicated the adaptive mechanisms of this species to phloridzin environments. The results deepened our understanding of the proteome in F. moniliforme in response to phloridzin inducers and provide a basis for further exploration for improving the efficiency of the fungi as biocontrol agents to control ARD.

scholarly journals Establishing a nurse-led thyroid cancer follow-up clinic

2021 ◽  
Vol 30 (4) ◽  
pp. S28-S35
Author(s):  
Andrew Fishburn ◽  
Nicola Fishburn
Keyword(s):  
Thyroid Cancer ◽  
Complex Disease ◽  
Disease Recurrence ◽  
Patient Survey ◽  
Safe Patient Care ◽  
Face To Face ◽  
Number Of Patients ◽  
Risk Of Disease

Thyroid cancer is a complex disease requiring management by a large multidisciplinary team. The number of patients with a diagnosis of thyroid cancer is significantly increasing year-on-year, and traditional models of consultant-led follow up are no longer sustainable. Although nurse-led cancer follow-up clinics are becomining increasingly common, thyroid cancer nurse-led follow-up clinics are rare. An excellent understanding of the disease, treatment and management of risk of disease recurrence is essential for safe patient care, and is discussed in this article. The clinic discussed uses the skill set of head and neck nurse specialists, including psychological support, coping strategies for long-term side effects of treatment and non-medical prescribing. A patient survey of the service revealed high levels of patient satisfaction and a desire to continue face-to-face consultations rather than telephone clinics.

scholarly journals miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1480
Author(s):  
Hiresh Ayoubian ◽  
Joana Heinzelmann ◽  
Sebastian Hölters ◽  
Oybek Khalmurzaev ◽  
Alexey Pryalukhin ◽  
...  
Keyword(s):  
Microarray Data ◽  
Expression Patterns ◽  
Hpv Infection ◽  
Differentially Expressed ◽  
Histological Subtypes ◽  
Specific Expression ◽  
Tissue Samples ◽  
Qrt Pcr ◽  
Differentially Expressed Mirnas ◽  
The Impact

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

scholarly journals Comprehensive Analysis of the Expression of Key Genes Related to Hippo Signaling and Their Prognosis Impact in Ovarian Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 344
Author(s):  
Paul Kubelac ◽  
Cornelia Braicu ◽  
Lajos Raduly ◽  
Paul Chiroi ◽  
Andreea Nutu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Prognostic Value ◽  
Prognostic Significance ◽  
Expression Level ◽  
Additional Patient ◽  
Tumor Control ◽  
Hippo Signaling ◽  
Patient Cohort ◽  
Qrt Pcr

The Hippo signaling pathway, one of the most conserved in humans, controlling dimensions of organs and tumor growth, is frequently deregulated in several human malignancies, including ovarian cancer (OC). The alteration of Hippo signaling has been reported to contribute to ovarian carcinogenesis and progression. However, the prognostic roles of individual Hippo genes in OC patients remain elusive. Herein we investigated the expression level and prognostic value of key Hippo genes in OC using online databases, followed by a qRT-PCR validation step in an additional patient cohort. Using the GEPIA database, we observed an increased level for TP53 and reduced expression level for LATS1, LATS2, MST1, TAZ, and TEF in tumor tissue versus normal adjacent tissue. Moreover, LATS1, LATS2, TP53, TAZ, and TEF expression levels have prognostic significance correlated with progression-free survival. The qRT-PCR validation step was conducted in an OC patient cohort comprising 29 tumor tissues and 20 normal adjacent tissues, endorsing the expression level for LATS1, LATS2, and TP53, as well as for two of the miRNAs targeting the TP53 gene, revealing miR-25-3p upregulation and miR-181c-5p downregulation. These results display that there are critical prognostic value dysregulations of the Hippo genes in OC. Our data demonstrate the major role the conserved Hippo pathway presents in tumor control, underlying potential therapeutic strategies and controlling several steps modulated by miRNAs and their target genes that could limit ovarian cancer progression.

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