FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions

Cezar-dos-Santos, Fernando; Ferreira, Rodolfo Sanches; Okuyama, Nádia Calvo Martins; Trugilo, Kleber Paiva; Sena, Michelle Mota; Pereira, Érica Romão; Pereira, Ana Paula Lombardi; Watanabe, Maria Angélica Ehara; Oliveira, Karen Brajão de

doi:10.1007/s00432-019-02951-x

Cited by 9 publications

(10 citation statements)

References 48 publications

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“…With the application and development of high‐throughput sequencing, gene chip in research of tumor genomics, it is significant to find the mechanism, prognostic factors, and potential therapeutic targets of cervical cancer. Some studies have reported that mutations of FOXP3 (Cezar‐Dos‐Santos et al, 2019), PIK3CA (Razia et al, 2019), XRCC4 (Gupta, Kushwah, Singh, & Banerjee, 2019), FBXW7 (Liu et al, 2019), and some copy number variations of KLF10 and PSG (Marrero‐Rodriguez et al, 2018) are related to the carcinogenesis and pathogenesis of cervical cancer, but they were not complete so that to be further studied. This study aim to better understand the characteristics of some genes and signaling pathways that associate with cervical cancer through bioinformatics.…”

Section: Introductionmentioning

confidence: 99%

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Yang

Xue

et al. 2020

Molec Gen & Gen Med

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Background Cervical cancer as one of the most common malignant tumors lead to bad prognosis among women. Some researches already focus on the carcinogenesis and pathogenesis of cervical cancer, but it is still necessary to identify more key genes and pathways. Methods Differentially expressed genes were identified by GEO2R from the gene expression omnibus (GEO) website, then gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzed by DAVID. Meanwhile, protein–protein interaction network was constructed by STRING, and both key genes and modules were found in visualizing network through Cytoscape. Besides, GEPIA did the differential expression of key genes and survival analysis. Finally, the expression of genes related to prognosis was further explored by UNLCAN, oncomine, and the human protein atlas. Results Totally 57 differentially expressed genes were founded, not only enriched in G1/S transition of mitotic cell cycle, mitotic nuclear division, and cell division but also participated in cytokine–cytokine receptor interaction, toll‐like receptor signaling pathway, and amoebiasis. Additionally, 12 hub genes and 3 key modules were screened in the Cytoscape visualization network. Further survival analysis showed that TYMS (OMIM accession number ), MCM2 (OMIM accession number ), HELLS (OMIM accession number ), TOP2A (OMIM accession number ), and CXCL8 (OMIM accession number ) were associated with the prognosis of cervical cancer. Conclusion This study aim to better understand the characteristics of some genes and signaling pathways about cervical cancer by bioinformatics, and could provide further research ideas to find new mechanism, more prognostic factors, and potential therapeutic targets for cervical cancer.

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Section: Introductionmentioning

confidence: 99%

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Yang

Xue

et al. 2020

Molec Gen & Gen Med

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“…Intron variants in genes can affect the mRNA alternative splicing process, thereby influencing the expression of corresponding proteins by disrupting transcription 25 . Evidence from patients with CC premalignant lesions has shown that the rs3761548 genotype AA protects women from HPV infection and high‐grade squamous intraepithelial lesion development by decreasing FOXP3 expression, whereas intron rs2232365 genotype GG increases the risk of HPV infection by promoting FOXP3 expression 13 . Accordingly, we deduced that rs2294021 and rs3761549 may influence FOXP3 expression levels.…”

Section: Discussionmentioning

confidence: 80%

“…Furthermore, variants in the intron region of a gene may affect mRNA splicing 11 . Importantly, FOXP3 is regarded as tumour initiation in CC cells, 12 and variants in the FOXP3 gene have been shown to be associated with HPV infection and precancerous lesions 13 . However, the relationships between FOXP3 gene variants and the risk of persistent HR‐HPV infection and CC remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

Shi

Pang

et al. 2022

J Cellular Molecular Medi

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The aim of this study was to investigate the effects of forkhead box protein P3 (FOXP3) intron single nucleotide variants (SNVs) in high‐risk human papilloma virus (HR‐HPV) infection and cervical cancer (CC) malignant lesions. We performed FOXP3 genotyping in 350 patients with CC and 350 healthy controls using the ImLDR multiple single nucleotide polymorphism genotyping technology. The heterozygous mutation TC in rs2294021 decreased the risk of HR‐HPV infection and CC malignant lesions (TC vs. TT: OR = 0.71, 95% CI = 0.51–0.99); the dominant model TC+CC and allele C in rs2294021 decreased the risk of CC malignant lesions (TC+CC vs. TT: OR = 0.69, 95% CI = 0.50–0.95; C vs. T: OR = 0.78, 95% CI = 0.63–0.97). The heterozygous mutation GA, dominant model GA+AA and allele A in rs3761549 also decreased the risk of HR‐HPV infection and CC malignant lesions (GA vs. GG: OR = 0.70, 95% CI = 0.51–0.96; GA+AA vs. GG: OR = 0.69, 95% CI = 0.51–0.94; A vs. G: OR = 0.75, 95% CI = 0.58–0.96). Patients with CC and HR‐HPV infection carrying rs2294021 TC and rs3761549 GA had lower expression of FOXP3 protein. Haplotype analysis revealed that T‐C‐A decreased the risk of HR‐HPV infection. Furthermore, we found a significant association between immune cells infiltration and prognosis in patients with CC. Our findings demonstrated that rs2294021 and rs3761549 variants may protect against HR‐HPV and CC malignant lesions by downregulating FOXP3 and that FOXP3 was associated with immune cells infiltration, which affected the prognosis of CC.

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“…DNA polymorphisms are a type of genetic variation that do not change the gene expression levels. Cezar-Dos-Santos et al (13) reported that the forkhead box P3 (FOXP3) rs3761548 homozygous genotype may be associated with the resistance to HPV infection, while the rs2232365 homozygous genotype (G/G) was a risk factor for HPV infection [odds ratio (OR)=2.10 (95% confidence interval (CI): 1.06-4.15)]. In addition, the Arg72Arg genotype and Arg72 alleles of tumor protein p53 (TP53) were also suggested to be related to the susceptibility of HPV infection [OR=1.85 (95% CI: 1.03-3.32) and 1.94 (95% CI: 1.20-3.15), respectively] (14).…”

Section: Dna Polymorphismsmentioning

confidence: 99%

Molecular alterations and clinical relevance in cervical carcinoma and precursors (Review)

Sheng

Xiang

et al. 2020

Oncol Rep

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Cervical cancer is one of the most common types of cancer and the fourth leading cause of cancer-related deaths in women. The occurrence and development of cervical cancer is a multifactorial and multilevel process, which usually occurs alongside a continuous high-risk human papillomavirus infection. With further developments in molecular biology and the advancement of sequencing technology, the role of biomarkers in cervical diseases has been gradually recognized. Therefore, it remains a priority to identify key molecular markers that can be used for the screening and triaging of the lesions. In recent years, numerous studies have been conducted in order to identify important markers for cervical diseases. The present review aimed to summarize the molecular alterations and clinical relevance of chromosomal alterations, DNA polymorphisms, the DNA methylation status, histone modifications, and alterations in microRNA and protein expression levels. Accumulating evidence suggests that molecular alterations may reflect the degree and the prognosis of the disease. Although significant progress has been made in the field of cervical cancer research, further samples and experiments are still required to identify crucial molecules.

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FOXP3 immunoregulatory gene variants are independent predictors of human papillomavirus infection and cervical cancer precursor lesions

Cited by 9 publications

References 48 publications

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Identification of key genes and pathways of diagnosis and prognosis in cervical cancer by bioinformatics analysis

Genetic association study of intron variants in the forkhead box protein P3 gene in Chinese patients diagnosed with cervical cancer

Molecular alterations and clinical relevance in cervical carcinoma and precursors (Review)

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