
浏览全部资源
扫码关注微信
1. 江苏医药职业学院,江苏 盐城 224001
2. 环境医学工程教育部重点实验室,东南大学公共卫生学院,江苏 南京 210009
3. 盐城市第一人民医院放疗科,江苏 盐城 224001
[ "王春桃(ORCID: 0000-0002-6391-3304),硕士,副教授,江苏医药职业学院科技处副处长 E-mail: yammy_taotao@163.com" ]
梁戈玉(ORCID: 0000-0002-5035-3088),博士,教授,东南大学人事处副处长 E-mail: gyliang@seu.edu.cn
收稿:2021-08-18,
修回:2022-03-02,
纸质出版:2022-04-30
移动端阅览
王春桃, 葛安兴, 吴红雁, 等. 不同级别子宫颈病变与lncRNA HOTTIP和H19单核苷酸多态性的关系研究[J]. 中国癌症杂志, 2022,32(4):324-334.
Chuntao WANG, Anxing GE, Hongyan WU, et al. The association between cervical lesions of different grades and lncRNA HOTTIP and H19 single nucleotide polymorphisms[J]. China Oncology, 2022, 32(4): 324-334.
王春桃, 葛安兴, 吴红雁, 等. 不同级别子宫颈病变与lncRNA HOTTIP和H19单核苷酸多态性的关系研究[J]. 中国癌症杂志, 2022,32(4):324-334. DOI: 10.19401/j.cnki.1007-3639.2022.04.005.
Chuntao WANG, Anxing GE, Hongyan WU, et al. The association between cervical lesions of different grades and lncRNA HOTTIP and H19 single nucleotide polymorphisms[J]. China Oncology, 2022, 32(4): 324-334. DOI: 10.19401/j.cnki.1007-3639.2022.04.005.
背景与目的:
HOTTIP和H19都是lncRNA(long non-coding RNA
lncRNA)中的一员
在肿瘤的发生、发展和迁移过程中发挥重要作用。本研究探讨HOTTIP rs2067087、H19 rs2839698和H19 rs2107425单核苷酸多态性(single nucleotide polymorphism
SNP)与
不同级别子宫颈病变发病风险的关系。
方法:
收集2018年11月
&
#x02014;2020年12月盐城市第一人民医院收治的345例子宫颈病变患者的外周静脉血及相关临床资料
其中子宫颈上皮内瘤变(cervical intraepithelial neoplasia
CIN)220例
子宫颈癌(cervical cancer
CC)125例
选取同期住院的360例无子宫颈病变患者为对照。采用TaqMan实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction
RTFQ-PCR)方法对2组人群中的
HOTTIP
基因的SNP位点rs2067087和
H
19基因的SNP位点rs2839698、rs2107425进行基因分型
采用
χ
2
检验和非条件logistic回归分析3个SNP位点与不同级别子宫颈病变的相关性。
结果:
与对照组相比
HOTTIP
rs2067087和
H
19 rs2839698在子宫颈病变患者中的基因型分布存在显著差异。在隐性模型中
携带
HOTTIP
rs2067087 GG基因型患者发生子宫颈病变的频率增加了52.2%(95% CI:1.021 ~ 2.269
P
<
0.05)
分层分析发现
该位点GG基因型主要增加了CIN的发病风险(OR=1.730
95% CI:1.117 ~ 2.680
P
<
0.05);与CC+CT基因型相比
携带
H
19 rs2839698 TT基因型患者发生子宫颈癌的风险减少了70.8%(95% CI:0.087 ~ 0.976
P
<
0.05)。未发现H19 rs2107425位点与不同级别子宫颈病变相关(
P
>
0.05)。
结论:
HOTTIP
基因SNP位点rs2067087与不同级别子宫颈病变相关
其GG基因型可能是宫颈上皮内瘤变发生的危险因素;
H
19基因SNP位点rs2839698与子宫颈癌发病风险相关
其TT基因型可能是子宫颈癌发生的保护因素。
Background and purpose:
Both HOTTIP and H19 are members of long non-coding RNA(lncRNA). They have been found to play an important role in the occurrence
development and migration of tumors. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of HOTTIP rs2067087
H19 rs2839698 and H19 rs2107425 and the risk of cervical lesions of different grades.
Methods:
The peripheral venous blood and related clinical data of 345 cases of cervical lesions were collected from Nov. 2018 to Dec. 2020 in Yancheng No.1 People's Hospital
including 220 cases of cervical intraepithelial neoplasia (CIN) and 125 cases of cervical cancer (CC). Three hundred and sixty patients without cervical lesions hospitalized during the same period were selected as the co
ntrol. TaqMan real-time fluorescence quantitative polymerase chain reaction (RTFQPCR) was used to genotype the HOTTIP SNP rs2067087
H19 SNP rs2839698 and rs2107425 in the two groups
and
&#x003c7;
2
test and unconditional logistic regression were used to analyze the association of the three SNP loci with cervical lesions of different grades.
Results:
Compared with the control group
there were significant differences in genotype distribution of HOTTIP rs2067087 and H19 rs2839698 in patients with cervical lesions. In the recessive model
the frequency of cervical lesions in patients with HOTTIP rs2067087 GG genotype increased by 52.2% (95% CI: 1.021-2.269
P
<
0.05). Stratified analysis showed that GG genotype at this locus mainly increased the risk of CIN (OR =1.730
95% CI: 1.117-2.680
P
<
0.05); Stratified analysis showed that the GG genotype at this locus mainly increased the risk of CIN (OR=1.730
95% CI:1.117-2.680
P
<
0.05). Compared with CC+CT genotype
the risk of cervical cancer in patients with H19 rs2839698 TT genotype was reduced by 70.8% (95% CI: 0.087-0.976
P
<
0.05). No correlation was found between H19 rs2107425 and cervical lesions of different grades (
P
>
0.05).
Conclusion:
HOTTIP rs2067087 SNP is associated with different levels of cervical lesions
and the GG genotype may be a risk factor for CIN; H19 rs2839698 SNP is associated with the risk of cervical cancer
and the TT genotype may be a protective factor for cervical cancer.
SUNG H , FERLAY J , SIEGEL R L , et al . Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J ] . CA Cancer J Clin , 2021 , 71 ( 3 ): 209 - 249 . DOI: 10.3322/caac.21660 http://doi.org/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660 https://onlinelibrary.wiley.com/doi/10.3322/caac.21660
XU R R , ZHANG X Y , XU Y , et al . Long noncoding RNA MST1P2 promotes cervical cancer progression by sponging with microRNA miR-133b [J ] . Bioengineered , 2021 , 12 ( 1 ): 1851 - 1860 . DOI: 10.1080/21655979.2021.1921550 http://doi.org/10.1080/21655979.2021.1921550 https://www.tandfonline.com/doi/full/10.1080/21655979.2021.1921550 https://www.tandfonline.com/doi/full/10.1080/21655979.2021.1921550
KUMARI S , BHOR V M . Association of cervicovaginal dysbiosis mediated HPV infection with cervical intraepithelial neoplasia [J ] . Microb Pathog , 2021 , 152 : 104780 . DOI: 10.1016/j.micpath.2021.104780 http://doi.org/10.1016/j.micpath.2021.104780 https://linkinghub.elsevier.com/retrieve/pii/S0882401021000528 https://linkinghub.elsevier.com/retrieve/pii/S0882401021000528
COHEN P A , JHINGRAN A , OAKNIN A , et al . Cervical cancer [J ] . Lancet , 2019 , 393 ( 10167 ): 169 - 182 . DOI: 10.1016/S0140-6736(18)32470-X http://doi.org/10.1016/S0140-6736(18)32470-X https://linkinghub.elsevier.com/retrieve/pii/S014067361832470X https://linkinghub.elsevier.com/retrieve/pii/S014067361832470X
ELSAYED E T , SALEM P E , DARWISH A M , et al . Plasma long non-coding RNA HOTAIR as a potential biomarker for gastric cancer [J ] . Int J Biol Markers , 2018 : 1724600818760244.
SHENG J Q , WANG M R , FANG D , et al . LncRNA NBR2 inhibits tumorigenesis by regulating autophagy in hepatocellular carcinoma [J ] . Biomedecine Pharmacother , 2021 , 133 : 111023 .
CHEN P Y , HSIEH P L , PENG C Y , et al. LncRNA MEG3 inhibits self-renewal and invasion abilities of oral cancer stem cells by sponging miR-421 [J ] . J Formos Med Assoc , 2021 , 120 ( 4 ): 1137 - 1142 . DOI: 10.1016/j.jfma.2020.09.006 http://doi.org/10.1016/j.jfma.2020.09.006 https://linkinghub.elsevier.com/retrieve/pii/S0929664620304290 https://linkinghub.elsevier.com/retrieve/pii/S0929664620304290
WANG K C , YANG Y W , LIU B , et al . A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression [J ] . Nature , 2011 , 472 ( 7341 ): 120 - 124 . DOI: 10.1038/nature09819 http://doi.org/10.1038/nature09819 https://doi.org/10.1038/nature09819 https://doi.org/10.1038/nature09819
RATAJCZAK M Z . Igf2-H19, an imprinted tandem gene, is an important regulator of embryonic development, a guardian of proliferation of adult pluripotent stem cells, a regulator of longevity, and a &#x02018;passkey&#x02019; to cancerogenesis [J ] . Folia Histochem Cytobiol , 2012 , 50 ( 2 ): 171 - 179 . DOI: 10.5603/FHC.2012.0026 http://doi.org/10.5603/FHC.2012.0026 http://czasopisma.viamedica.pl/fhc/article/view/19347 http://czasopisma.viamedica.pl/fhc/article/view/19347
OU L , WANG D Z , ZHANG H , et al . Decreased expression of miR-138-5p by lncRNA H19 in cervical cancer promotes tumor proliferation [J ] . Oncol Res , 2018 , 26 ( 3 ): 401 - 410 . DOI: 10.3727/096504017X15017209042610 http://doi.org/10.3727/096504017X15017209042610 https://www.ingentaconnect.com/content/10.3727/096504017X15017209042610 https://www.ingentaconnect.com/content/10.3727/096504017X15017209042610
刘芳 . 长链非编码RNA HOTTIP影响宫颈癌细胞增殖、迁移及侵袭能力的研究 [D ] . 合肥 : 安徽大学 , 2015 .
WOJCIK G L , KAO W H L , DUGGAL P . Relative performance of gene- and pathway-level methods as secondary analyses for genome-wide association studies [J ] . BMC Genet , 2015 , 16 : 34 . DOI: 10.1186/s12863-015-0191-2 http://doi.org/10.1186/s12863-015-0191-2 http://www.biomedcentral.com/1471-2156/16/34 http://www.biomedcentral.com/1471-2156/16/34
WANG Y C , TSAO S M , LI Y T , et al . The relationship between long noncoding RNA H19 polymorphism and the epidermal growth factor receptor phenotypes on the clinicopathological characteristics of lung adenocarcinoma [J ] . Int J Environ Res Public Health , 2021 , 18 ( 6 ): 2862 . DOI: 10.3390/ijerph18062862 http://doi.org/10.3390/ijerph18062862 https://www.mdpi.com/1660-4601/18/6/2862 https://www.mdpi.com/1660-4601/18/6/2862
WANG B G , LI Y Z , DING H X , et al . HOTTIP polymorphism may affect gastric cancer susceptibility by altering HOTTIP expression [J ] . Biosci Rep , 2020 , 40 ( 8 ): BSR20191687.
TONG Y S , WANG X W , ZHOU X L , et al . Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma [J ] . Mol Cancer , 2015 , 14 : 3 . DOI: 10.1186/1476-4598-14-3 http://doi.org/10.1186/1476-4598-14-3 http://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-14-3 http://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-14-3
YANG J , WANG Y Y , ZHANG S , et al . The association of TNF-&#x003b1; promoter polymorphisms with genetic susceptibility to cervical cancer in a Chinese Han population [J ] . Int J Gen Med , 2022 , 15 : 417 - 427 .
ALI M A , SHAKER O G , EZZAT E M , et al . Association between rs1859168/HOTTIP expression level and colorectal cancer and adenomatous polyposis risk in Egyptians [J ] . J Interferon Cytokine Res , 2020 , 40 ( 6 ): 279 - 291 . DOI: 10.1089/jir.2019.0105 http://doi.org/10.1089/jir.2019.0105 https://www.liebertpub.com/doi/10.1089/jir.2019.0105 https://www.liebertpub.com/doi/10.1089/jir.2019.0105
WANG B G , XU Q , LV Z , et al . Association of twelve polymorphisms in three onco-lncRNA genes with hepatocellular cancer risk and prognosis: a case-control study [J ] . World J Gastroenterol , 2018 , 24 ( 23 ): 2482 - 2490 . DOI: 10.3748/wjg.v24.i23.2482 http://doi.org/10.3748/wjg.v24.i23.2482 http://www.wjgnet.com/1007-9327/full/v24/i23/2482.htm http://www.wjgnet.com/1007-9327/full/v24/i23/2482.htm
LV Z , XU Q , SUN L P , et al . Four novel polymorphisms in long non-coding RNA HOTTIP are associated with the risk and prognosis of colorectal cancer [J ] . Biosci Rep , 2019 , 39 ( 5 ): BSR20180573.
于洁 , 卢博奇 , 朱丽业 , 等 . 长链非编码RNA H19靶向Bcl-2的表达调控宫颈癌细胞侵袭转移行为的机制 [J ] . 解放军医药杂志 , 2019 , 31 ( 1 ): 12 - 17 .
YU J , LU B Q , ZHU L Y , et al . Mechanism of long-chain non-coding RNA H19 targeting bcl-2 expression for regulating invasion and metastasis of cervical cancer cells [J ] . Med Pharm J Chin People&#x02019;s Liberation Army , 2019 , 31 ( 1 ): 12 - 17 .
YANG C , TANG R , MA X , et al . Tag SNPs in long non-coding RNA H19 contribute to susceptibility to gastric cancer in the Chinese Han population [J ] . Oncotarget , 2015 , 6 ( 17 ): 15311 - 15320 . DOI: 10.18632/oncotarget.3840 http://doi.org/10.18632/oncotarget.3840 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.3840 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.3840
WU E R , CHOU Y E , LIU Y F , et al . Association of lncRNA H19 gene polymorphisms with the occurrence of hepatocellular carcinoma [J ] . Genes (Basel ), 2019 , 10 ( 7 ): E506 .
LIU C H , CHEN L S , YOU Z H , et al . Association between lncRNA H19 polymorphisms and cancer susceptibility based on a meta-analysis from 25 studies [J ] . Gene , 2020 , 729 : 144317 . DOI: 10.1016/j.gene.2019.144317 http://doi.org/10.1016/j.gene.2019.144317 https://linkinghub.elsevier.com/retrieve/pii/S037811191930976X https://linkinghub.elsevier.com/retrieve/pii/S037811191930976X
YU B Q , CHEN J Y , HOU C F , et al. LncRNA H 19 gene rs2839698 polymorphism is associated with a decreased risk of colorectal cancer in a Chinese Han population: a case-control study [J ] . J Clin Lab Anal , 2020 , 34 ( 8 ): e23311 .
HASHEMI M , MOAZENI-ROODI A , SARABANDI S , et al . Association between genetic polymorphisms of long noncoding RNA H19 and cancer risk: a meta-analysis [J ] . J Genet , 2019 , 98 : 81 . DOI: 10.1007/s12041-019-1126-x http://doi.org/10.1007/s12041-019-1126-x https://doi.org/10.1007/s12041-019-1126-x https://doi.org/10.1007/s12041-019-1126-x
HUANG M C , CHOU Y H , SHEN H P , et al . The clinicopathological characteristic associations of long non-coding RNA gene H19 polymorphisms with uterine cervical cancer [J ] . J Cancer , 2019 , 10 ( 25 ): 6191 - 6198 . DOI: 10.7150/jca.36707 http://doi.org/10.7150/jca.36707 http://www.jcancer.org/v10p6191.htm http://www.jcancer.org/v10p6191.htm
YANG P J , HSIEH M J , HUNG T W , et al . Effects of long noncoding RNA H19 polymorphisms on urothelial cell carcinoma development [J ] . Int J Environ Res Public Health , 2019 , 16 ( 8 ): E1322 .
HUANG M C , CHOU Y H , SHEN H P , et al . The clinicopathological characteristic associations of long non-coding RNA gene H19 polymorphisms with uterine cervical cancer [J ] . J Cancer , 2019 , 10 ( 25 ): 6191 - 6198 . DOI: 10.7150/jca.36707 http://doi.org/10.7150/jca.36707 http://www.jcancer.org/v10p6191.htm http://www.jcancer.org/v10p6191.htm
0
浏览量
1446
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621