Plasminogen Activator Inhibitor-1 and Susceptibility to Lung Cancer: A Population Genetics Perspective

Bayramoglu, Aysegul; Güneş, Hasan Veysi; Metintaş, Muzaffer; Degirmenci, I.; Güler, Halil İbrahim; Ustuner, Cengiz; Musmul, Ahmet

doi:10.1089/gtmb.2014.0061

Cited by 6 publications

(5 citation statements)

References 23 publications

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“…Nevertheless, PAI-1 and/or HMGB1 levels may be important prognostic factors for lung cancer. 54 , 55 , 59 …”

Section: Discussionmentioning

confidence: 99%

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer

Niki¹,

Yokoi²,

Kurata³

et al. 2017

LCTT

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BackgroundSeveral biomarkers have emerged as potential prognostic and predictive markers for non-small-cell lung cancer (NSCLC). Successful inhibition of angiogenesis with the antivascular endothelial growth factor antibody, bevacizumab, has improved the efficacy seen with standard cytotoxic therapy of NSCLC. However, despite such enhanced treatment strategies, the prognosis for patients with advanced NSCLC remains poor.Patients and methodsWe assessed potential biomarkers in 161 NSCLC patients and 42 control patients. Enzyme-linked immunosorbent assay methods were used to evaluate three biomarkers: platelet-derived microparticle (PDMP), high-mobility group box-1 (HMGB1), and plasminogen activator inhibitor-1 (PAI-1). We studied the effects of bevacizumab on the expression of these markers. We also analyzed the relationship of the newly designed risk factor (NDRF) to overall survival and disease-free survival. The NDRF classification of patients was determined from the levels of PDMP, HMGB1, and PAI-1. To determine the individual prognostic power of PDMP, HMGB1, and PAI-1, we evaluated associations between their levels and patient outcomes by Kaplan–Meier survival analysis in a derivation cohort.ResultsPDMP, HMGB1, and PAI-1 levels were higher in NSCLC patients compared with control patients. Notably, the difference in PDMP levels exhibited the strongest statistical significance (p<0.001). Multivariate analysis showed that HMGB1 and PAI-1 levels were significantly correlated with PDMP levels. Patients who received standard chemotherapy with bevacizumab exhibited significantly reduced levels of all three markers compared with patients who received standard chemotherapy. NDRF3 status (high levels of all three markers) was significantly correlated with a poor prognosis (p<0.05 for overall survival and disease-free survival).ConclusionOur results demonstrate that abnormal levels of PDMP, HMGB1, and PAI-1 are related to each other in NSCLC. Moreover, our findings suggest that the vascular complications associated with these markers may contribute to a poor prognosis for NSCLC patients.

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“…Nevertheless, PAI-1 and/or HMGB1 levels may be important prognostic factors for lung cancer. 54 , 55 , 59 …”

Section: Discussionmentioning

confidence: 99%

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer

Niki¹,

Yokoi²,

Kurata³

et al. 2017

LCTT

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“…No other articles were found from the references manually. A total of 37 articles were identified in this article, which included 33 articles with 9550 cases and 10431 controls samples for the rs1799889 polymorphism, 8,12 -43 5 articles with 2705 cases and 3168 controls samples for the rs2227631 polymorphism 23,38,41,44,45 and 4 articles with 2799 cases and 4011 controls samples for the rs2227667 polymorphism. 44 -47…”

Section: Resultsmentioning

confidence: 99%

PAI-1 Polymorphisms Have Significant Associations With Cancer Risk, Especially Feminine Cancer

Peng

Guo

Li³

2021

Technol Cancer Res Treat

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Background: The plasminogen activator inhibitor-1 (PAI-1) was found in many types of tumor cells, which involved in tumorigenesis. Some studies investigated the associations between PAI-1 polymorphisms and various cancers, but the results were inconsistent. So this study did a meta-analysis to assess the strength of relationship between PAI-1 and cancer. Methods: Articles that meet the requirements were searched from PubMed, EMBASE, MEDLINE, Scopus, CNKI, Wanfang and SinoMed electronic databases before June 17th 2021. Stata version 11.2 was performed to merge the odds ratios (ORs) values and calculate 95% confidence intervals (CIs). Stratified analyses were assessed on the basis of types of cancer, ethnicity and source of the control group. Heterogeneity and sensitivity analysis were tested, and publication bias was also estimated. A meta-regression analysis was applied to explore sources of heterogeneity. The false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) test were used to assess the credibility of statistically significant associations. Results: Ultimately, in this study, 33 eligible reports were included with 9550 cases and 10431 controls for the rs1799889 polymorphism, 5 reports with 2705 cases and 3168 controls for the rs2227631 polymorphism, and 4 reports with 2799 cases and 4011 controls for the rs2227667 polymorphism. The ORs and 95% CIs showed a statistically significant relationship between rs1799889 4G>5G polymorphism and cancer risk, especially in feminine cancer. The term refers to cancers that occur in the female reproductive system, such as ovarian, breast, endometrial and cervical cancer. Moreover, there was no association observed for the PAI-1 promoter A>G polymorphism (rs2227631 and rs2227667). In further subgroup analyses of 4G>5G polymorphism (rs1799889), an increased susceptibility to cancer was observed in Caucasians group and some types of cancer groups. Conclusions: This article comes to a conclusion that the rs1799889 polymorphism might help to increase the risk of cancer; moreover, the susceptibility to feminine cancer is more evident.

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“…Genomic DNA was isolated using the DNA isolation Kit (EZ-10 Spin Colon Blood Genomic DNA Minipreps Kit, Biotechnology Department Bio Basic Inc., Markham, Ontario, Canada). PCR was performed using the following primers (for the 4G allele: 5' -GTC TGG ACA CGT GGG GA-3'; for the 5G allele: 5' -GTC TGG ACA CGT GGG GG-3'; Downstream primer: 5' -TGC AGC CAG CCA CGT GAT TGT CTA G-3'; Upstream primer: 5'-AAG CTT TTA CCA TGG TAA CCC CTG GT-3') (Integrated DNA Technologies Inc., Leuven, Belgium) and the PCR mixture containing 50 µg genomic DNA, 1XPCR buffer, 0.2 mM dNTP mixture, 50 pmol allele-specific primers, 50 pmol common downstream primer, 2.5 pmol control upstream primer, and 25 U Taq polymerase in a 25 µl total volume (11). The following cycling conditions were set: the pre-denaturation step of 3 min at 94°C, denaturation of 35 cycles of 1 min at 94°C, annealing of 1 min at 54°C, and the extension step of 1 min at 72°C, followed by the single-cycle final extension step at 72°C for five min, using a Thermal Cycler T100 (Bio-Rad, Foster City, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The PAI-1 gene (accession No. P05121) is located on chromosome 7 (q 21.3-q 22), spans 12.3 kb of DNA, and contains 9 exons and 8 introns (10)(11)(12)(13). The 4G/5G (rs1799889) polymorphism is located in the PAI-1 gene promoter region and is caused by the insertion/deletion variation of guanosine that is located 675 bases upstream from the gene's transcriptional starting point (11).…”

Section: Introductionmentioning

confidence: 99%

The role of rs1799889 genetic variation in Type 2 diabetes and Diabetic Nephropathy risk

Bayramoğlu¹,

Bayramoğlu²,

Güler³

2020

Erciyes Med J

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Type 2 diabetes mellitus (T2 DM) represents a complex metabolic disease with genetic heterogeneity and increasing worldwide prevalence. One of the candidate genes associated with T2 DM and diabetic nephropathy (DN) is the plasminogen activator inhibitor-1 (PAI-1) gene. The present research aimed to reveal the polymorphism frequencies of the PAI-1 gene 4G/5G and to investigate the role of this polymorphism in T2 DM and DN development. Materials and Methods: The genomic DNA of the 261 individuals was included in this study. The polymerase chain reaction (PCR) method with 4G and 5G allele-particular primers was used to identify the polymorphism of PAI-1 4G/5G. The PCR products were evaluated using a CCD camera after 2% agarose gel electrophoresis. Results: Although the frequencies of the gene genotypes differed statistically significant between 80 patients and 51 patients with and without DN, respectively, and the control group, no statistically significant difference was detected between those with and without DN. The 5G/5G genotype was found to be significantly higher in the patient group. Conclusion: The findings suggest that there is a significant correlation between variants of the PAI-1 gene and the risk for T2 DM formation.

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Plasminogen Activator Inhibitor-1 and Susceptibility to Lung Cancer: A Population Genetics Perspective

Abstract: This study found a statistically significant difference between the groups with respect to genotype distribution. Consequently, we can say that the PAI-1 gene 4G/5G polymorphism is associated with lung cancer in Turkey.

Cited by 6 publications

References 23 publications

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer

New prognostic biomarkers and therapeutic effect of bevacizumab for patients with non-small-cell lung cancer

PAI-1 Polymorphisms Have Significant Associations With Cancer Risk, Especially Feminine Cancer

The role of rs1799889 genetic variation in Type 2 diabetes and Diabetic Nephropathy risk

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