scholarly journals Expression of MMP and TIMP mRNA in Peripheral Blood Leukocytes of Patients with Invasive Ductal Carcinoma of the Breast

2016 ◽  
Vol 31 (3) ◽  
pp. 309-316
Author(s):  
Edyta Wieczorek ◽  
Michal Galicki ◽  
Bartlomiej Tomasik ◽  
Magdalena Krol ◽  
Ewa Jablonska ◽  
...  

Purpose An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) appears critical for tumor progression and metastasis. This study aimed to determine whether gene expression of MMP1, MMP2, MMP9, TIMP1 and TIMP3 and the MMP/TIMP expression ratio in peripheral blood leukocytes (PBLs) and the MMP1 and TIMP1 contents or MMP1/TIMP1 ratio in plasma were associated with clinicopathological characteristics in invasive ductal carcinoma (IDC) of the breast. Materials and methods Blood samples were collected from women newly diagnosed with IDC who had not received prior treatment (n = 102). Gene expression in PBLs was analyzed by quantitative real-time polymerase chain reaction. Concentrations of MMP1 and TIMP1 in plasma were measured using ELISA. Results In univariate analysis the expression levels of MMP2 and TIMP1 mRNA were significantly higher in premenopausal compared to postmenopausal patients (p<0.001 and p = 0.014, respectively). MMP2 mRNA expression negatively correlated with age (p<0.001, r = -0.43). We found that the MMP2/TIMP3 expression ratio was significantly higher in women after menopause (p = 0.007). The MMP2/TIMP1 expression ratio was higher in human epidermal growth factor receptor 2 (HER2)-positive patients (p = 0.022). Low-grade tumors had significantly lower MMP1/TIMP1 and MMP2/TIMP1 expression ratios (p = 0.047 and p = 0.048, respectively). TIMP1 plasma concentration was significantly higher in small tumors compared with T2-T3 tumors (p = 0.013). Conclusions These findings reveal an important association between tumor characteristics and expression ratios of MMP1/TIMP1 and MMP2/TIMP1 in PBLs and TIMP1 concentration in plasma. Menopausal status may influence the mRNA expression levels of MMP2 and TIMP1 as well as the MMP2/TIMP3 expression ratio in IDC of the breast.

2021 ◽  
Vol 8 ◽  
Author(s):  
Yao Fan ◽  
Jun Gao ◽  
Yinghui Li ◽  
Xuefei Chen ◽  
Ting Zhang ◽  
...  

Objective: Abnormal lipid metabolism has a close link to the pathophysiology of schizophrenia (SZ). This study mainly aimed to evaluate the association of variants at apolipoprotein A1 (APOA1) and APOA4 with SZ in a Chinese Han population.Methods: The rs5072 of APOA1 and rs1268354 of APOA4 were examined in a case–control study involving 2,680 patients with SZ from the hospital and 2,223 healthy controls screened by physical examination from the community population. The association was estimated with the odds ratio (OR) and 95% confidence intervals (95% CIs) by logistic regression. The APOA1 and APOA4 messenger RNA (mRNA) in peripheral blood leukocytes were measured by real-time PCR and compared between SZ cases and controls. Serum apoA1 levels were detected by turbidimetric inhibition immunoassay and high-density lipoprotein cholesterol (HDL-C) levels were detected by the homogeneous method.Results: Both of the rs5072 of APOA1 and rs1268354 of APOA4 had statistically significant associations with SZ. After adjustment for age and sex, ORs (95% CIs) of the additive model of rs5072 and rs1268354 were 0.82 (0.75–0.90) and 1.120 (1.03–1.23), and p-values were 3.22 × 10−5 and 0.011, respectively. The association of rs5072 with SZ still presented statistical significance even after Bonferroni correction (p-value×6). SZ patients during the episode presented lower levels of apoA1, HDL-C, mRNA of APOA1 common variants and transcript variant 4, and APOA4 mRNA than controls (p &lt; 0.01) while SZ patients in remission showed a significantly decreased APOA1 transcript variant 3 expression level and increased APOA4 mRNA expression level (p &lt; 0.01). mRNA expression levels of APOA1 transcript variant 4 significantly increased with the variations of rs5072 in SZ during the episode (ptrend = 0.017). After the SZ patients received an average of 27.50 ± 9.90 days of antipsychotic treatment, the median (interquartile) of serum apoA1 in the SZ episode significantly increased from 1.03 (1.00.1.20) g/L to 1.08 (1.00.1.22) g/L with the p-value of 0.044.Conclusion: Our findings suggest that the genetic variations of APOA1 rs5072 and APOA4 rs1268354 contribute to the susceptibility of SZ, and the expression levels of APOA1 and APOA4 mRNA of peripheral blood leukocytes decreased in SZ patients during the episode while APOA4 increased after antipsychotic treatment.


2005 ◽  
Vol 52 (3,4) ◽  
pp. 137-144 ◽  
Author(s):  
Kazuhito Rokutan ◽  
Kyoko Morita ◽  
Kiyoshi Masuda ◽  
Kumiko Tominaga ◽  
Michiyo Shikishima ◽  
...  

2018 ◽  
Vol 90 (3) ◽  
pp. 21-24
Author(s):  
I E Malysheva ◽  
O V Balan ◽  
E L Tikhonovich ◽  
T O Volkova

Aim. To study the expression level of the genes DROSHA and DICER in peripheral blood leukocytes (PBL) of patients with sarcoidosis of the lungs Materials and methods. The study included 32 patients diagnosed with persistent lung sarcoidosis (mean age 41.56±1.27 years) and 36 healthy donors (control; mean age 42.79±1.95 years). The level of expression of messenger RNA (mRNA) of the genes DROSHA and DICER were determined in PBL of healthy donors and patients with sarcoidosis of the lung by polymerase chain reaction in real time. Results. As a result of the conducted researches it is established that the level of drosha gene expression in PBL patients with sarcoidosis of lungs is significantly reduced in comparison with the control (p


2020 ◽  
Vol 22 (4) ◽  
pp. 665-674
Author(s):  
L. V. Gankovskaya ◽  
L. V. Stakhovskaya ◽  
V. V. Grechenko ◽  
E. A. Koltsova ◽  
O. S. Uvarova ◽  
...  

Pathogenesis of ischemic stroke  is actively  involved  in the  system  of innate immunity. Under conditions of cerebral  ischemia, a number of biologically  active  substances are  released  that  interact with innate immunity receptors, in particular TLR2  and  TLR4, which  exacerbate inflammation in brain  tissue. Identification of predictor markers  at the level of the innate immunity system may foresee the clinical course of ischemic stroke and ensure timely treatment. Our objective was to study expression of TLR2 and TLR4 receptors in peripheral blood leukocytes  in patients with ischemic stroke in the dynamics of the disease. 27 people  were included in the study. The main  group consisted of patients with ischemic stroke of varying severity (n = 19). Patients of the main  group were divided into two subgroups:  with an NIHSS index value of < 10 (n = 10) and > 10 (n = 9). The control group included healthy  donors  with no history  of acute  and chronic inflammatory diseases (n = 8). Peripheral blood  leukocytes  were used as the  test material. To determine expression  of the TLR2  and TLR4  genes, RT-PCR in real time was used. Surface  expression  of TLRs was determined by flow cytometry. A study of the TLR2 and TLR4 gene expression showed that on the 1st, 3rd  and 7th  day post-stroke, the TLR4 gene expression  in patients was significantly  increased, when compared to the control group (p < 0.01), whereas TLR2 gene expression on the 3rd  day of the disease was not statistically different from the control group. A study of surface expression  of receptors showed that the average TLR2 fluorescence intensity on the patients’ peripheral blood monocytes was significantly  increased on the 1st  and 3rd  day of disease when compared to the control group.  The  surface  expression  of TLR4  on monocytes has a statistically significant  increase  only on day 7. Assessment  of surface expression  of TLRs in subgroups  with different  severity values by NIHSS showed that  patients with a NIHSS index > 10 had a significantly  higher  level of surface of TLR2  expression  over the observation period, while the largest difference in TLR4  expression  in the subgroups  was observed  on the 1st day of the disease (p < 0.05). Patients with ischemic stroke showed an increase  in TLR2 and TLR4 expression at the gene and protein level, compared to healthy  donors. These indices can be considered possible predictors for clinical  prognosis  of ischemic stroke.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yi Sun ◽  
Yeying Wen ◽  
Qishuang Ruan ◽  
Le Yang ◽  
Shuna Huang ◽  
...  

Abstract Background The present study aims to investigate the complete long non-coding RNA (lncRNA) and messenger RNA (mRNA) expression profiles in Intracranial aneurysm (IA) patients and controls by RNA sequencing, which reveals the lncRNA with predictive value for IA risk. Methods The comprehensive lncRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs), followed by bioinformatics analyses, such as GO analysis, KEGG pathway analysis, and CNC network construction. Subsequently, qRT-PCR was used to profile the expression levels of selected lncRNA (lncRNA ENST000000576153, lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1, lncRNA ENST00000508090 and lncRNA ENST00000579688) in 30 (small) or 130 (large) peripheral blood leukocytes, respectively. Multivariate logistic regression was utilized to analyze the effects of lncRNA on IA. Receiver operating characteristic (ROC) curve was further drawn to explore the value of lncRNA in predicting IA. Results Totally 900 up-regulated and 293 down-regulated lncRNAs, as well as 1297 up-regulated and 831 down-regulated mRNAs were discovered in sequencing. Enrichment analyses revealed that they were actively involved in immune/inflammatory response and cell adhesion/extracellular matrix. Co-expression analysis and further enrichment analyses showed that five candidate lncRNAs might participate in IA’s inflammatory response. Besides, after controlling other conventional risk factors, multivariate logistic regression analysis disclosed that low expression of lncRNA ENST00000607042, lncRNA ENST00000471220, lncRNA ENST00000478738, lncRNA MALAT1 in peripheral blood leukocytes were independent risk factors for IA. LncRNA ENST00000607042 has superior diagnostic value for IA. Conclusions This study reveals the complete lncRNAs expression profiles in IA. The inflammatory response was closely related to IA. Besides, lncRNA ENST00000607042 might be a novel biomarker for IA risk.


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