scholarly journals LncRNAs, MALAT1 and lnc-DC as potential biomarkers for multiple sclerosis diagnosis

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Olfat G. Shaker ◽  
Rania H. Mahmoud ◽  
Omayma O. Abdelaleem ◽  
Enas G. Ibrahem ◽  
Abdelrahmaan A. Mohamed ◽  
...  

AbstractLong non-coding RNAs (lncRNAs) play an important role in gene regulation and show greater tissue specificity and complexity of biological functions. There is on-going research in their contribution in autoimmune diseases like multiple sclerosis (MS). Our study aimed at the evaluation of serum levels of lncRNAs, MALAT1 and lnc-DC in MS patients and the investigation of the association between these lncRNAs and the disease activity. Serum from 45 MS patients and 45 healthy controls was separated. MALAT1 and lnc-DC expression levels were assayed by qRT-PCR. MALAT1 and lnc-DC were significantly increased in MS patients (P=0.004 and P=0.006, respectively) in comparison with controls. There was a significant increase in expression of MALAT1 in secondary progressive MS (SPMS) subgroup compared with controls (P<0.0001); however, significant elevation of lnc-DC was demonstrated in relapsing remitting MS (RRMS) subtype (P=0.003) compared with normal controls. A positive association between the expression levels of MALAT1 and lnc-DC (r = 0.513, P < 0.0001) in MS patients was detected. Moreover, positive correlation was observed between MALAT1and lnc-DC in RRMS (r = 0.569, P = 0.001). Serum levels of MALAT1 and lnc-DC may serve as potential novel molecular biomarkers for MS diagnosis and may provide a new direction for its treatment.

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 301
Author(s):  
Amal Ahmed Abd El-Fattah ◽  
Nermin Abdel Hamid Sadik ◽  
Olfat Gamil Shaker ◽  
Amal Mohamed Kamal ◽  
Nancy Nabil Shahin

Long non-coding RNAs play an important role in tumor growth, angiogenesis, and metastasis in several types of cancer. However, the clinical significance of using lncRNAs as biomarkers for breast cancer diagnosis and prognosis is still poorly investigated. In this study, we analyzed the serum expression levels of lncRNAs PVT1, HOTAIR, NEAT1, and MALAT1, and their associated proteins, PAI-1, and OPN, in breast cancer patients compared to fibroadenoma patients and healthy subjects. Using quantitative real-time PCR (qRT-PCR), we compared the serum expression levels of the four circulating lncRNAs in patients with breast cancer (n = 50), fibroadenoma (n = 25), and healthy controls (n = 25). The serum levels of PAI-1 and OPN were measured using ELISA. Receiveroperating-characteristic (ROC) analysis and multivariate logistic regression were used to evaluate the diagnostic value of the selected parameters. The serum levels of HOTAIR, PAI-1, and OPN were significantly higher in breast cancer patients compared to controls and fibroadenoma patients. The serum level of PVT1 was significantly higher in breast cancer patients than in the controls, while that of NEAT1 was significantly lower in breast cancer patients compared to controls and fibroadenoma patients. Both ROC and multivariate logistic regression analyses revealed that PAI-1 has the greatest power in discriminating breast cancer from the control, whereas HOTAIR, PAI-1, and OPN have the greatest power in discriminating breast cancer from fibroadenoma patients. In conclusion, our data suggest that the serum levels of PVT1, HOTAIR, NEAT1, PAI-1, and OPN could serve as promising diagnostic biomarkers for breast cancer.


2008 ◽  
Vol 389 (6) ◽  
Author(s):  
Isobel A. Scarisbrick ◽  
Rachel Linbo ◽  
Alexander G. Vandell ◽  
Mark Keegan ◽  
Sachiko I. Blaber ◽  
...  

Abstract Tissue kallikrein KLK1 and the kallikrein-related peptidases KLK2–15 are a subfamily of serine proteases that have defined or proposed roles in a range of central nervous system (CNS) and non-CNS pathologies. To further understand their potential activity in multiple sclerosis (MS), serum levels of KLK1, 6, 7, 8 and 10 were determined in 35 MS patients and 62 controls by quantitative fluorometric ELISA. Serum levels were then correlated with Expanded Disability Status Scale (EDSS) scores determined at the time of serological sampling or at last clinical follow-up. Serum levels of KLK1 and KLK6 were elevated in MS patients (p≤0.027), with highest levels associated with secondary progressive disease. Elevated KLK1 correlated with higher EDSS scores at the time of serum draw and KLK6 with future EDSS worsening in relapsing remitting patients (p≤0.007). Supporting the concept that KLK1 and KLK6 promote degenerative events associated with progressive MS, exposure of murine cortical neurons to either kallikrein promoted rapid neurite retraction and neuron loss. These novel findings suggest that KLK1 and KLK6 may serve as serological markers of progressive MS and contribute directly to the development of neurological disability by promoting axonal injury and neuron cell death.


2006 ◽  
Vol 12 (3) ◽  
pp. 247-252 ◽  
Author(s):  
Bodil Petersen ◽  
Klaus Bendtzen ◽  
Nils Koch-Henriksen ◽  
Mads Ravnborg ◽  
Christian Ross ◽  
...  

Objective The main objective was to follow serum levels of neutralizing antibodies (NABs) against interferon-beta (IFNβ) after discontinuation of IFNβ therapy. Background A large proportion of patients treated with recombinant IFNβ for multiple sclerosis (MS) develop therapy-induced NABs. Knowledge of persistence of NABs after discontinuation of therapy is limited. Design/patients: A retrospective follow-up study of patients treated in Denmark for relapsing-remitting (RR) MS with IFNβ for at least 12 months. NAB-positive patients, who discontinued therapy, were followed up with measurements of NABs. Methods We measured NAB-neutralizing capacity and NAB titres a.m. Kawade using a clinically validated cytopathic effect assay. Results Thirty-seven patients were included. Mean follow-up time was 22 months. Of the 29 patients with a NAB titre at or above 25 prior to termination of therapy, only three patients reverted to a titre below 25. Of these, two had a titre below 200 and one patient a titre of 600 at the last examination before treatment stop. The longest post-treatment follow-up during which a patient maintained NAB positivity was 59 months. Conclusion NABs against IFNβ, especially with high titres, tend to persist for a long time after discontinuation of IFNβ therapy. NABs should always be measured before reinstitution of IFNβ treatment in NAB-positive patients.


2009 ◽  
Vol 15 (11) ◽  
pp. 1280-1285 ◽  
Author(s):  
Trygve Holmøy ◽  
Stine Marit Moen ◽  
Thomas A Gundersen ◽  
Michael F Holick ◽  
Enrico Fainardi ◽  
...  

Hypovitaminosis D may play a role in multiple sclerosis (MS), but little is known about intrathecal vitamin D. 25-Hydroxyvitamin D was measured in cerebrospinal fluid and sera from 36 patients with relapsing-remitting MS, 20 patients with other inflammatory neurological diseases and 18 patients with non-inflammatory neurological diseases with liquid chromatography-mass spectrometry. There were no significant differences in cerebrospinal fluid concentrations of 25-hydroxyvitamin D, but the cerebrospinal fluid:serum ratio was significantly lower in MS compared with other inflammatory neurological diseases (p=0.0012) and non-inflammatory neurological diseases (p=0.041) patients. The concentrations of 25-hydroxyvitamin D in cerebrospinal fluid and serum were positively correlated and their ratio was similar to that of albumin. Neither the concentrations of 25-hydroxyvitamin D in cerebrospinal fluid or serum nor their ratio were associated with the presence of relapses or gadolinium-enhanced lesions. These results do not support that 25-hydroxyvitamin D is actively transported to the cerebrospinal fluid, or that the cerebrospinal fluid or serum levels or their ratio exert a major impact on MS activity.


2008 ◽  
Vol 69 (4-5) ◽  
pp. 235-240 ◽  
Author(s):  
Juan Luís Fernández-Morera ◽  
Sandra Rodríguez-Rodero ◽  
Carlos Lahoz ◽  
Alberto Tuñon ◽  
Aurora Astudillo ◽  
...  

2015 ◽  
Vol 18 (1) ◽  
pp. 113-119 ◽  
Author(s):  
Anna M. Witkowska ◽  
Katarzyna Socha ◽  
Jan Kochanowicz ◽  
Elżbieta Karpińska ◽  
Marta Jakoniuk ◽  
...  

Introduction: Although much is known about cytokines and adhesion molecules during an active course of multiple sclerosis (MS), there is limited information about their serum levels during remission. Objective: This study aimed to (1) compare peripheral levels of tumor necrosis factor-α (TNF-α), soluble interleukin-2 receptor α (sIL-2Rα), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble E-selectin (sE-selectin) in MS patients during clinical remission with those of healthy controls and (2) explore possible relationships between the levels of these cytokines and adhesion molecules and neurological impairment. Methods: Initially, 92 patients with relapsing-remitting multiple sclerosis (RRMS) who were in clinical remission and 30 healthy controls were recruited for this study. The severity of neurological impairment was assessed with the Expanded Disability Status Scale (EDSS). Serum concentrations of TNF-α, sIL-2Rα, sICAM-1, and sE-selectin were determined using the sandwich enzyme-linked immunosorbent (ELISA) technique and compared between patients and controls. In a subset of RRMS patients ( n = 67), the levels of these cytokines and adhesion molecules were compared between subgroups of patients based on scores on the EDSS subscales, which measure disability level for specific neurological functions. Results: The MS patients’ TNF-α, sICAM-1, and sE-selectin levels were markedly lower than those of the controls, while their sIL-2Rα level was higher. The serum sICAM-1 concentration was positively associated with EDSS total score (ρ = .291, p = .017) as well as with the EDSS pyramidal (ρ = .267, p = .029) and cerebellar subscores (ρ = .303, p = .013). In the patients with cerebellar deficits and severe brain stem dysfunction, sICAM-1 levels were upregulated. Conclusion: Although a decreased sICAM-1 concentration was observed in RRMS patients in remission as compared to healthy controls, sICAM-1 seemed to reflect neurological impairment and clinical disability. These data suggest that increasing serum sICAM-1 levels may be associated with progression of cerebellar or brain stem perturbations. However, further studies are required to confirm these findings in a larger population of RRMS patients.


1998 ◽  
Vol 4 (3) ◽  
pp. 254-256 ◽  
Author(s):  
P D Mehta ◽  
S D Cook ◽  
P K Coyle ◽  
R A Troiano ◽  
C S Constantinescu ◽  
...  

We measured free kappa (k) and lambda (l) light chains in urine from patients with definite multiple sclerosis (MS), other neurologic diseases (OND), and normal controls by using an enzyme linked immunosorbent assay. Both k and l light chains were higher in MS than OND or controls. In seven of eight relapsing-remitting (R-R) MS patients serial studies showed that urinary k chains were elevated during periods of worsening, and decreased during clinical recovery. In contrast, the levels of k chains did not correlate with clinical activity in 10 progressive (P) MS patients. Further correlation of urinary light chains with neurologic evaluations in R-R and P MS patients over a longer period are needed to determine their clinical and biological relevance.


Sign in / Sign up

Export Citation Format

Share Document