Promoter Hypermethylation Analysis of Host Genes in Cervical Cancer Patients With and Without Human Immunodeficiency Virus in Botswana.
Promoter Hypermethylation Analysis of Host Genes in Cervical Cancer Patients With and Without Human Immunodeficiency Virus in Botswana.
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博茨瓦纳有和无人类免疫缺陷病毒的宫颈癌患者宿主基因启动子超甲基化分析。
DOI：
10.3389/fonc.2021.560296
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发表时间：
2021
影响因子：
4.7
通讯作者：
Narasimhamurthy M
中科院分区：
文献类型：
--
作者：
Tawe L;Grover S;Zetola N;Robertson ES;Gaseitsiwe S;Moyo S;Kasvosve I;Paganotti GM;Narasimhamurthy M
背景：人类免疫缺陷病毒（HIV）的流行与宫颈癌相互关联。宫颈病变中宿主基因启动子的DNA高甲基化也被认为是宫颈癌进展的一个促成因素。
方法：为此，我们分析了四个肿瘤抑制基因（RARB、CADM1、DAPK1和PAX1）的启动子甲基化情况，并在博茨瓦纳对已知HIV感染状况的女性探讨了它们与宫颈癌可能存在的关联。总共使用了228份宫颈标本（128例宫颈癌和100例非癌症受试者）。采用耶茨校正卡方检验和费舍尔精确检验来探究每个宿主基因的启动子甲基化与癌症状态之间的关联。随后，进行逻辑回归分析以找出哪些因素，即HIV感染状况、高危型人乳头瘤病毒（HPV）基因型、患者年龄和启动子甲基化，与以下因变量相关：癌症状态、宫颈癌分期和启动子甲基化率。
结果：在宫颈癌患者中，所研究的所有基因中观察到的启动子甲基化率均大于64%。分析还表明，随着甲基化启动子基因数量的增加，患宫颈癌的风险更高（比值比 = 6.20；95%置信区间：3.66 - 10.51；P < 0.001）。与其他基因相比，RARB甲基化与宫颈癌的关联最强（比值比 = 15.25；95%置信区间：6.06 - 40.0；P < 0.001）。宫颈癌以及RARB和DAPK1基因的启动子甲基化与年龄增长相关（比值比 = 1.12；95%置信区间：1.01 - 1.26；P = 0.037和比值比 = 1.05；95%置信区间：1.00 - 1.10；P = 0.040）。在宫颈癌患者中，这些基因的表观遗传变化似乎与HIV感染状况无关。此外，我们发现宫颈癌分期受RARB（χ² = 7.32；P = 0.002）和CADM1（χ² = 12.68；P = 0.013）高甲基化以及HIV感染状况（χ² = 19.93；P = 0.001）的影响。
结论：本研究证实了浸润性宫颈癌与癌症部位肿瘤抑制基因的启动子基因甲基化之间的关联。在博茨瓦纳的这组宫颈癌患者中，HIV感染与甲基化变化没有任何关联。需要进一步的研究来更好地理解HIV在癌症患者中宿主基因甲基化导致宫颈癌进展过程中的作用。
Background: Epidemics of human immunodeficiency virus (HIV) and cervical cancer are interconnected. DNA hypermethylation of host genes' promoter in cervical lesions has also been recognized as a contributor to cervical cancer progression. Methods: For this purpose we analyzed promoter methylation of four tumor suppressor genes (RARB, CADM1, DAPK1 and PAX1) and explored their possible association with cervical cancer in Botswana among women of known HIV status. Overall, 228 cervical specimens (128 cervical cancers and 100 non-cancer subjects) were used. Yates-corrected chi-square test and Fisher's exact test were used to explore the association of promoter methylation for each host gene and cancer status. Subsequently, a logistic regression analysis was performed to find which factors, HIV status, high risk-HPV genotypes, patient's age and promoter methylation, were associated with the following dependent variables: cancer status, cervical cancer stage and promoter methylation rate. Results: In patients with cervical cancer the rate of promoter methylation observed was greater than 64% in all the genes studied. Analysis also showed a higher risk of cervical cancer according to the increased number of methylated promoter genes (OR = 6.20; 95% CI: 3.66–10.51; P < 0.001). RARB methylation showed the strongest association with cervical cancer compared to other genes (OR = 15.25; 95% CI: 6.06–40.0; P < 0.001). Cervical cancer and promoter methylation of RARB and DAPK1 genes were associated with increasing age (OR = 1.12; 95% CI: 1.01-1.26; P = 0.037 and OR = 1.05; 95% CI: 1.00-1.10; P = 0.040). The presence of epigenetic changes at those genes appeared to be independent of HIV status among subjects with cervical cancer. Moreover, we found that cervical cancer stage was influenced by RARB (χ2= 7.32; P = 0.002) and CADM1 (χ2=12.68; P = 0.013) hypermethylation, and HIV status (χ2= 19.93; P = 0.001). Conclusion: This study confirms the association between invasive cervical cancer and promoter gene methylation of tumor suppressing genes at the site of cancer. HIV infection did not show any association to methylation changes in this group of cervical cancer patients from Botswana. Further studies are needed to better understand the role of HIV in methylation of host genes among cancer subjects leading to cervical cancer progression.
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DOI：
10.1158/1055-9965.epi-17-1051
发表时间：
2018-12
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Gradissimo A;Lam J;Attonito JD;Palefsky J;Massad LS;Xie X;Eltoum IE;Rahangdale L;Fischl MA;Anastos K;Minkoff H;Xue X;D'Souza G;Flowers LC;Colie C;Shrestha S;Hessol NA;Strickler HD;Burk RD
通讯作者：
Burk RD
影响因子：
16
作者：
Gross AM;Jaeger PA;Kreisberg JF;Licon K;Jepsen KL;Khosroheidari M;Morsey BM;Swindells S;Shen H;Ng CT;Flagg K;Chen D;Zhang K;Fox HS;Ideker T
通讯作者：
Ideker T
DOI：
10.1073/pnas.93.18.9821
发表时间：
1996-09-03
影响因子：
11.1
作者：
Herman, JG;Graff, JR;Baylin, SB
通讯作者：
Baylin, SB
影响因子：
3.7
作者：
Ermel A;Ramogola-Masire D;Zetola N;Tong Y;Qadadri B;Azar MM;Brown DR
通讯作者：
Brown DR
影响因子：
5.3
作者：
Mikovits, JA;Young, HA;Ruscetti, FW
通讯作者：
Ruscetti, FW