ASSOCIATION OF EXPRESSION OF NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2 GENES WITH BIOCHEMICAL REMEDIATION IN PATIENTS WITH LOCALIZED PROSTATE CANCER

Aim. To identify the association of NFKB1, HIF1, VEGFA, VEGFB, BAX, BCL2 gene expression in prostate adenocarcinoma cells with biochemical recurrence of localized prostate cancer. Patients and methods. Three groups of patients were formed in the study – the main one, the comparison group and the control group. In patients with prostate cancer (PC) in the main group (n = 56) with biochemical recurrence (BR) for two years after radical surgery, as well as in 60 patients without BR (experimental group) by real-time PCR in prostate cancer tissue the expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2 was determined. The control group consisted of 55 patients in whom, when performing diagnostic punctures for benign prostate tumors, biopsy specimens were taken in healthy tissues. The age of patients in the three groups ranged from 57 to 74 years (median 63 years). When quantifying expression of genes NFKB1, HIF1, VEGFA, VEGFВ, BAX, BCL2, the difference in the values of reaction threshold cycles (Ct) fixed for the studied and reference genes was determined. The relative level (Expr) was the ratio of Ct medians for each gene in two compared groups of the studied three ones: in the main group to the indicator in the control group, in the experimental group to the indicator in the control group, and also between the main group and the experimental group. Results. A comparative analysis of gene expression in prostate cancer tissue in the main group compared with the experimental group showed a statistically significant increase (p < 0,05) in the relative index for the HIF1 gene (2,7 times), the VEGFA gene (2,4 times ) and the NFKB1 gene (2 times). Consequently, in patients with localized early recurrence prostate cancer, initially in the prostate tissue, a higher level of expression of the NFKB1, HIF1 and VEGFA genes was established. In the experimental group relative to the control group, the expression of the proapoptic gene BAX was 1,6 times higher (p < 0,05), and for the antiapoptic gene BCL2 no changes were detected (p = 0,09). Thus, in patients with localized prostate cancer in the absence of BR, after radical prostatectomy, an initial increase in the expression of the BAX gene promoted the activation of apoptosis. In patients with localized prostate cancer, subsequent biochemical recurrence initially in the tissue of prostate adenocarcinoma inhibition of apoptosis due to increased expression of the BCL2 gene was observed. Conclusion. Enhancement of NFKB1, VEGFA, HIF1 and BCL2 gene expression in prostate tissue is associated with the development of BR in patients with localized prostate cancer.

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CHANGES IN GENE EXPRESSION ASSOCIATED WITH NON-CANCER EFFECTS OF THE CHORNOBYL CLEAN-UP WORKERS IN THE REMOTE PERIOD AFTER EXPOSURE

Проблеми радіаційної медицини та радіобіології = Problems of Radiation Medicine and Radiobiology ◽

10.33145/2304-8336-2020-25-456-477 ◽

2020 ◽

Vol 25 ◽

pp. 456-477

Author(s):

I. Ilienko ◽

◽

D. Bazyka ◽

N. Golyarnyk ◽

L. Zvarych ◽

...

Keyword(s):

Gene Expression ◽

Real Time ◽

Real Time Pcr ◽

Main Group ◽

Control Group ◽

Chronic Obstructive ◽

Relative Level ◽

Gstm1 Gene ◽

Expression Of Genes ◽

Immune Inflammation

Objective. to establish the connection of radiation-induced changes in gene expression with the realized pathology of the broncho-pulmonary and cardiovascular systems in Chornobyl clean-up workers. Materials and methods. We examined 314 male Chornobyl clean-up workers (main group; age (58.94 ± 6.82) years (M ± SD); min 33, max 79 years; radiation dose (411.82 ± 625.41) mSv (M ± SD); min 1.74, max 3600 mSv) with various nosological forms of cardiovascular and broncho-pulmonary pathology (BPP) and 50 subjects of the control group: age (50.50 ± 5.73) years (M ± SD); min 41, max 67 years. The relative level of BCL2, CDKN2A, CLSTN2, GSTM1, IFNG, IL1B, MCF2L, SERPINB9, STAT3, TERF1, TERF2, TERT, TNF, TP53, CCND1, CSF2, VEGFA genes expression was determined in peripheral blood leukocytes by real-time PCR (7900 HT Fast Real-Time PCR System (Applied Biosystems, USA)). The «gene-disease» association was determined on statistical models stratified separately for each disease and gene. Logistic regression was used to calculate the odds ratio. Results. Increased GSTM1 gene expression and no changes in angiogenesis-related VEGFA gene expression were found in the main group of patients with coronary heart disease (CHD). It was established overexpression of TP53, VEGF and IFNG genes in the group of patients with arterial hypertension (AH). At combination of these diseases an increase of expression of СSF2, TERF1, TERF2 genes was established. The detected changes demonstrate an activation of the antioxidative defense system in patients with CHD, while AH is associated with the expression of genes of angiogenesis and immune inflammation. It was shown an increase in the expression of genes associated with apoptosis and kinase activity (BCL2, CLSTN2, CDKN2), immune inflammation (CSF2, IL1B, TNF) in Chornobyl clean-up workers with BPP. Expression of TP53 and GSTM1 (gene, associated with the glutathione system) was significantly upregulated in the group of individuals with chronic bronchitis, whereas in patients with chronic obstructive pulmonary disease, no increase was detected; the expression of SERPINB9 and MCF2L genes was downregulated. Conclusions. Changes in the expression of genes, associated with the development of somatic pathology in the remote period after irradiation, in particular the genes of the immune response and inflammatory reactions CSF2, IFNG, IL1B, TNF; expression of genes that regulate cell proliferation, aging and apoptosis TP53, BCL2, MCF2L, CDKN2A, SERPINB9, TERF1, TERF2, TERT; genes that regulate cell adhesion and angiogenesis CLSTN2, VEGF. Key words: gene expression, somatic pathology, radiation, Chornobyl.

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Prognostic significance of the evaluation of expression of the gene PCA3 in urine in patients with localized prostate cancer and histomorphological changes in the peritumoral zone

Urologicheskie vedomosti ◽

10.17816/uroved8311-19 ◽

2018 ◽

Vol 8 (3) ◽

pp. 11-19

Author(s):

Philip S. Bova

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Biochemical Recurrence ◽

Prognostic Significance ◽

Intraepithelial Neoplasia ◽

Disease Recurrence ◽

Localized Prostate Cancer ◽

Urine Sediment ◽

Increased Risk ◽

Urine Exosomes

Aim. To determine the prognostic significance PCA3 gene expression in urine sediment and exosomes in patients with localized prostate cancer (PC) and associated histologic changes in the peritumoral zone as a predictor of biochemical recurrence after radical prostatectomy (RPE). Materials and methods. Of 148 patients with localized PC, 96 (65%) had high-grade prostatic intraepithelial neoplasia (PIN-2) in the peritumoral zone. The other 52 (35%) had no pathologic tissue of the peritumoral zone. PDA3 expression in urine sediment and exosomes was determined with real-time PCR with respect to the reference gene KLK3. Results. The PCA3 gene expression level in urine exosomes in patients with PIN-2 in the prostatic peritumoral zone and synchronous pancreatic adenocarcinoma was higher among patients with subsequent disease recurrence. Increased PCA3 gene expression in the urine sediment was also predictive of the risk of recurrence of a prostatic tumor with PIN-2 in the peritumoral zone, although to a lesser degree than the results with urine exosomes. When the ∆Ct РСА3-KLK3 was ≥1,86 in the urine sediment, biochemical recurrence of PC and PIN-2 developed more frequently in the peritumoral zone (84% versus 51%, p = 0,013). Conclusions. Increased PCA3 gene expression in urine sediment and exosomes is a predictor of increased risk of biochemical recurrence after RPE in patients with localized PC and PIN-2 in the peritumoral zone.

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The expression levels of microRNAs that have the androgen receptor in localized prostate cancer as a target.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.206 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 206-206

Author(s):

Katia Ramos Moreira Leite ◽

Manuel Garcia Florez ◽

Sabrina Thalita Reis ◽

Nayara Viana ◽

Betina S. Katz ◽

...

Keyword(s):

Prostate Cancer ◽

Metastatic Disease ◽

Biochemical Recurrence ◽

Protein Translation ◽

Localized Prostate Cancer ◽

Control Group ◽

Prostate Hyperplasia ◽

Control Of Gene Expression ◽

Expression Levels ◽

The Mean

206 Background: Prostate cancer (PC) depends on the androgen activity being the androgen blockage the main treatment in the setting of metastatic disease. Mechanisms of resistance in metastatic tumors are not completely known. MicroRNAs (miRNA) are small non-coding molecules that have as canonical mechanism the negative control of gene expression promoting messenger RNA (mRNA) degradation or impairing protein translation. The role of miRNAs that have as target the AR are still unknown. Our objective is to study the expression profile of miRNAs that have AR as target in localized prostate cancer. Methods: The expression levels of miRNAs that have as target AR (miR9, 34a, 34c, 185, 130a, 299, 421, 371, 541) were studied using qRT-PCR in the surgical specimens of 83 patients that underwent radical prostatectomy to treat localized prostate cancer. The expression levels of miRNAs were correlated to Gleason score (GS), pre-operatory PSA, pathological stage and biochemical recurrence (PSA>0.2 ng/mL) in a mean follow up of 45.9 months. The mean age was 62.9, mean GS was 7.2, mean PSA was 7.93 ng/mL, and 42 (50.6%) patients were staged pT2. Twenty-four (28.9%) patients presented biochemical recurrence. Specimens of six patients submitted to open surgery to treat benign prostate hyperplasia (BPH) composed the control group. Results: The mean expression of AR was 1.63, being overexpressed in 59% of the cases. The mean expression levels of the nine studied miRNAs was miR9=3.06, miR34a=0.76, miR34c=1.14, miR185=1.65, miR130a=1.9, miR299=6.23, miR421=2.84, miR371=1.41, and miR541=0.93. The univariate analysis showed that pT2 tumors have higher expression of miR371(p=0.009). Conclusions: In localized PC the higher expression of miR371 is related with organ-confined disease. This miRNA could be important in the control of AR and the comprehension of its role in PC might bring alternatives to treat metastatic disease. Funded by FAPESP – 2012/50163-0.

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HYPOXIA-DEPENDANT MECHANISMS OF REGULATING NEOANGIOGENESIS AND APOPTOSIS IN PATIENTS WITH EARLY RECURRENT LOCALIZED PROSTATE CANCER

Cancer Urology ◽

10.17650/1726-9776-2018-14-3-37-42 ◽

2018 ◽

Vol 14 (3) ◽

pp. 37-42

Author(s):

O. I. Kit ◽

F. S. Bova ◽

A. Yu. Maksimov

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Tumor Tissue ◽

Prostate Gland ◽

Early Recurrence ◽

Localized Prostate Cancer ◽

Control Group ◽

Expression Of Genes ◽

Comparative Group

Objective. Examination of the expression of genes responsible for hypoxia-dependent control of transcription, neoangiogenesis, and apoptosis in tumor tissue of the prostate, in patients with localized prostate cancer (РС) with biochemical recurrence (BR) and without recurrences after radical prostatectomy (RPE).Materials and methods. The main group included 56 patients with localized PC who had been diagnosed with BR within two years after RP. 60 patients with localized PC who did not relapse had a comparative group. 55 patients in whom operative biopsy specimens of the prostate gland were taken within healthy tissues with the removal of benign prostatic hyperplasia were combined into a control group. Determination of the expression level of the BAX, BCL2, VEGFA and HIF1α genes in tumor tissue was performed by real-time polymerase chain reaction.Results. In patients with localized PC after RPE, development of BR is associated with an increase in the expression of BCL2, VEGFA and HIF1α genes and a decrease in the expression of the BAX gene. In patients with localized PC and early recurrence of tumor tissue through a hypoxia-dependent factor that enhances transcritical processes in tumor cells, neoangiogenesis is activated, which is associated with inhibition of apoptosis of tumor cells by enhancing the expression of the antiapoptotic gene BCL2.Conclusion. Determination of the expression of BAX, BCL2, VEGFA and HIF1α genes in tumor tissue with localized PC allows further assessment of the risk of disease progression after surgical treatment.

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