Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cardoso, Maria de Fátima Senra; Castelletti, Carlos Henrique Madeiros; Lima-Filho, José Luiz de; Martins, Danyelly Bruneska Gondim; Teixeira, J. A.

doi:10.1016/j.mrrev.2017.06.002

Cited by 45 publications

(28 citation statements)

References 109 publications

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“…Although persistent hr-HPV infection is the main cause of cervical cancer development, genetic alterations may impact on the risk of this neoplasia. Thus, genetic markers may be useful in the screening of pre-neoplastic and neoplastic cervical lesions, especially in cases of persistent HPV infections or recurrent cytological abnormalities [7,41]. Moreover, the conventional methods used for screening cervical cancer cannot differentiate pre-neoplastic cervical lesions that will regress or persist and progress.…”

Section: Discussionmentioning

confidence: 99%

3’UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

Silva

Santos

Nogueira³

et al. 2020

BMC Cancer

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Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in one-carbon metabolism. Methods: Our sample consisted of 106 women, divided into two groups-Remission (n = 60), i.e., with the presence of pre-neoplastic lesions at first meeting (T 1) and normal cytology after 6 months of follow-up (T 2), and Persistence (n = 46), i.e., with the presence of pre-neoplastic lesions at T 1 and T 2. We obtained cervical samples for cytological analysis (T 1 and T 2), HPV detection (T 1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756G of Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5′-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide 1494 in TS 3′-untranslated region (TS3'UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms. However, the risk of persistence was higher among women with the heterozygote genotype-ins/del [OR (IC95%): 3.22 (1.19-8.69), p = 0.021], or the polymorphic genotypedel/del [OR (IC95%): 6.50 (1.71-24.70), p = 0.006] of TS3'UTR. Conclusions: The presence of the TS3'UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent pre-neoplastic cervical lesions.

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Section: Discussionmentioning

confidence: 99%

3’UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

Silva

Santos

Nogueira³

et al. 2020

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Although persistent hr-HPV infection is the main cause of cervical cancer development, genetic alterations may impact on the risk of this neoplasia. Thus, genetic markers may be useful in the screening of pre-neoplastic and neoplastic cervical lesions, especially in cases of persistent HPV infections or recurrent cytological abnormalities (7,33). Moreover, the conventional methods used for screening cervical cancer cannot differentiate pre-neoplastic cervical lesions that will regress or persist and progress.…”

Section: ) Discussionmentioning

confidence: 99%

3’UTR Polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

Silva

Santos

Nogueira³

et al. 2020

Preprint

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Background: Cervical cancer is caused by high-risk Human Papillomavirus (hr-HPV) infection associated with cofactors that has been analyzed as predictors of the remission or persistence of cytological abnormalities remission or persistence. These cofactors can be either environmental, epigenetic, or genetic. Polymorphism in genes of enzymes that act on one-carbon metabolism alter their activity and also may be associated with cervical carcinogenesis because they affect DNA synthesis and repair, and gene expression. Therefore, this study aimed to analyze the risk of persistence of pre-neoplastic cervical lesions according to genetic polymorphisms involved in onecarbon metabolism. Our sample consisted of 106 women, divided into two groups -Remission (n=60), i.e., with the presence of pre-neoplastic lesions at first meeting (T1) and normal cytology after six months of follow-up (T2), and Persistence (n=46), i.e., with the presence of pre-neoplastic lesions at T1 and T2. We obtained cervical samples for cytological analysis (T1 and T2), HPV detection (T1), and evaluation of polymorphism C667T of Methylenetetrahydrofolate Reductase (MTHFR C677T), A2756Gof Methionine Synthase (MS A2756G), A66G of Methionine Synthase Reductase (MTRR A66G), double or triple 28 bp tandem repeat in 5'-untranslated enhanced region of Thymidylate Synthase (TSER), and 6 bp deletion at nucleotide1494 in TS 3'-untranslated region (TS3'UTR). To analyze all genetic polymorphisms simultaneously, we calculated the Genetic Risk Score (GRS). Results: We observed no differences between the Remission and Persistence groups regarding the GRS. Also, there were no differences in the genotypic and allelic distribution of MTHFR C677T and MS A2756G polymorphisms.However, the risk of persistence was higher among women with the heterozygote genotype -ins/del OR (IC95%): 3.22 (1.19 -8.69), p=0.021, or the polymorphic genotype -del/del OR (IC95%): 6.50(1.71 -24.70), p=0.006 of TS3'UTR. Conclusions: The presence of the TS3'UTR polymorphism increased the risk of persistence of cervical abnormalities. This genetic variant could be a potential marker of cervical carcinogenesis and therefore assist the follow-up of women with persistent preneoplastic cervical lesions. 1) BackgroundPersistent high-risk Human Papillomavirus (hr-HPV) infection is the main cause of cervical cancer.3 However, only 10% of the women infected by hr-HPV develop pre-neoplastic lesions and less than 1% progress to cervical cancer. Only approximately 30% of high-grade cervical lesions progress to uterine cervix cancer, and spontaneous regression occurs in 20-40% of the cases (1-4). Thus, the risk of cervical carcinogenesis depends on hr-HPV infection and host-dependent features (5, 6).Environmental, genetic, and epigenetic cofactors of cervical carcinogenesis has been analyzed as markers for diagnosis, prognosis, and for auxiliary the treatment of pre-neoplastic cervical lesions since they could be predictors of cytological abnormalities remission or persistence (7-10).Several genetic alteration...

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“…APC, CDH1, GSTP1, RARB, RASSF1, MGMT, SOC51, CDH13, DAPK1, MLH1, PTEN, FHIT TIMP3 and VHL. These genes are frequently methylated in cervical cancer and associated with higher disease severity [55][56][57][58]. Several epigenetic modulatory agents have been known to lower TSG promoter methylation, restore transcription and contribute to apoptosis induction [16,59,60].…”

Section: Discussionmentioning

confidence: 99%

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

Sundaram

Unni

Somvanshi

et al. 2019

Genes

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Background: Several epigenetic changes are responsible for transcriptional alterations of signaling pathways and tumour suppressor genes (TSGs) contributing to carcinogenesis. This study was aimed to examine the effect of the phytochemical, genistein on various molecular targets in HeLa cells. Methods: Quantitative PCR was used to analyze the expression of various molecular targets. Biochemical assays were employed to study the epigenetic enzymes. To correlate the transcriptional status of the selected TSGs and epigenetic modulation, their promoter 5'CpG methylation levels were evaluated by quantitative methylation array followed by methylation specific restriction digestion. Results: The expression of several genes involved in the cell cycle regulation, migration, inflammation, phosphatidylinositol 3-kinase (PI3K) and mitogen activated kinase-like protein (MAPK) pathway were found to be modulated including CCNB1, TWIST1, MMP14, TERT, AKT1, PTPRR, FOS and IL1A. Genistein modulated the expression of DNA methyltransferases (DNMTs), histone deacetylases (HDACs), histone methyltransferases (HMTs), demethylases, and histone phosphorylases. Furthermore, genistein decreased the activity of DNMTs, HDACs, and HMTs and reduced global DNA methylation levels. Promoter methylation of several TSGs, including FHIT, RUNX3, CDH1, PTEN, and SOC51, was lowered with corresponding transcriptional increase. Network analysis indicated similar effect of genistein. Conclusion: This study presents a comprehensive mechanism of action of genistein showcasing effective epigenetic modulation and widespread transcriptional changes resulting in restoration of tumour suppressor gene expression. This study corroborates the development of genistein as a candidate for anti-cancer therapy.

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Putative biomarkers for cervical cancer: SNVs, methylation and expression profiles

Cited by 45 publications

References 109 publications

3’UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

3’UTR polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

3’UTR Polymorphism of Thymidylate Synthase gene increased the risk of persistence of pre-neoplastic cervical lesions

Genistein Modulates Signaling Pathways and Targets Several Epigenetic Markers in HeLa Cells

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