血清miR-18a、miR-485-5p对HPV阳性宫颈癌的诊断价值

李丹萍; 李宗民; 张丽峡; 杨伟伟; 李巧莉

doi:10.16766/j.cnki.issn.1674-4152.002860

血清miR-18a、miR-485-5p对HPV阳性宫颈癌的诊断价值

doi: 10.16766/j.cnki.issn.1674-4152.002860

1.
黄河三门峡医院妇科，河南三门峡 472000
2.
黄河三门峡医院放疗科，河南三门峡 472000

基金项目:

河南省科技发展计划项目 182102510069

详细信息

通讯作者:
李丹萍，E-mail：sdjs1205@163.com

中图分类号: R737.33 R730.43
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- 文章访问数: 127
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- PDF下载量: 4
- 被引次数: 0
出版历程
- 收稿日期: 2022-01-29
- 网络出版日期: 2023-04-20

Diagnostic value of serum miR-18a and miR-485-5p for HPV-positive cervical cancer

1.
Department of Gynaecology, Yellow River Sanmenxia Hospital, Sanmenxia, Henan 472000, China

摘要

摘要: 目的探讨宫颈癌患者伴人乳头瘤病毒(HPV)与单纯宫颈癌患者血清微小RNA(miR)-18a，miR-485-5p表达差异，分析二指标对HPV阳性宫颈癌的诊断价值。方法选取2020年1月—2021年1月黄河三门峡医院收治的91例HPV阳性宫颈癌患者为HPV阳性宫颈癌组，62例HPV阳性非宫颈癌妇女为HPV阳性组，57名体检健康妇女为对照组，采用qRT-PCR检测血清miR-18a、miR-485-5p的表达。采用受试者操作特征曲线(ROC)分析血清miR-18a、miR-485-5p对HPV阳性宫颈癌的诊断价值。结果 HPV阳性宫颈癌组血清miR-18a表达高于对照组和HPV阳性组，而miR-485-5p表达低于对照组和HPV阳性组(均P＜0.05)。血清miR-18a、miR-485-5p表达与HPV阳性宫颈癌患者FIGO分期、间质浸润深度、是否淋巴结转移有关(均P＜0.05)。ROC曲线显示，miR-18a、miR-485-5p、联合诊断HPV阳性宫颈癌的AUC分别为0.752、0.802、0.876，灵敏度分别为67.03%、75.82%、83.52%，特异度分别为77.42%、74.19%、83.87%。联合诊断HPV阳性宫颈癌的AUC大于miR-18a、miR-485-5p单独诊断(均P＜0.05)。结论 HPV阳性宫颈癌血清miR-18a高表达，miR-485-5p低表达，可作为HPV阳性宫颈癌辅助诊断指标。
- 宫颈癌 /
- 人乳头瘤病毒 /
- 微小RNA-18a /
- 微小RNA-485-5p
Abstract: Objective To explore the difference of serum MicroRNA (miR)-18a and miR-485-5p expression between cervical cancer patients with human papillomavirus (HPV) and simple cervical cancer patients, and analyze the diagnostic value of the two indicators for HPV-positive cervical cancer. Methods A total of 91 patients with HPV-positive cervical cancer admitted to Yellow River Sanmenxia Hospital from January 2020 to January 2021 were selected as the HPV-positive cervical cancer group. Sixty-two women with HPV-positive non-cervical cancer were placed in the HPV-positive group, and 57 healthy women based on physical examination were placed in the control group. Serum miR-18a and miR-485-5p expression was detected by qRT-PCR. Receiver operating characteristic (ROC) curve was used to analyse the diagnostic value of two indicators for HPV-positive cervical cancer. Results The expression of serum miR-18a in HPV-positive cervical cancer group was higher, while the expression of miR-485-5p was lower than those in the control group and HPV-positive cervical cancer group (P < 0.05). Serum miR-18a and miR-485-5p expression was associated with FIGO stage, depth of interstitial infiltration and lymph node metastasis in patients with HPV-positive cervical cancer (P < 0.05). The ROC curves showed that the area under the curve (AUC) for miR-18a and miR-485-5p and their combination for the diagnosis of HPV-positive cervical cancer were 0.752, 0.802 and 0.876, respectively, with sensitivities of 67.03%, 75.82% and 83.52%, and specificities of 77.42%, 74.19% and 83.87%, respectively. The AUC of the combined diagnosis of HPV-positive cervical cancer was greater than that of miR-18a and miR-485-5p alone (P < 0.05). Conclusion High expression of serum miR-18a and low expression of miR-485-5p in HPV-positive cervical cancer can be used as an auxiliary diagnostic indicator for HPV-positive cervical cancer.
- Cervical cancer /
- Human papillomavirus /
- MicroRNA-18a /
- MicroRNA-485-5p

HTML全文

图 1 血清miR-18a、miR-485-5p表达诊断HPV阳性宫颈癌的ROC曲线

Figure 1. ROC curve of serum miR-18a and miR-485-5p expression in diagnosis of HPV-positive cervical cancer

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表 1 3组血清miR-18a、miR-485-5p表达水平比较(x±s)

Table 1. The expression levels of serum miR-18 a, miR-485-5p in three groups (x±s)

组别	例数	miR-18a	miR-485-5p
HPV阳性宫颈癌组	91	2.43±0.51^ab	1.27±0.21^ab
HPV阳性组	62	1.93±0.58^a	1.59±0.30^a
对照组	57	1.29±0.17	2.00±0.35
F值		109.472	116.430
P值		＜0.001	＜0.001
注：与对照组比较，^aP＜0.05；与HPV阳性组比较，^bP＜0.05。

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表 2 miR-18a、miR-485-5p表达与HPV阳性宫颈癌患者临床病理特征的关系(x±s)

Table 2. Relationship between miR-18a and miR-485-5p expression and clinicopathological features of patients with HPV-positive cervical cancer (x±s)

项目	例数	miR-18a	t值	P值	miR-485-5p	t值	P值
年龄
≥45岁	52	2.47±0.51	0.781	0.437	1.26±0.23	-0.309	0.758
＜45岁	39	2.38±0.51			1.28±0.20
病理类型
鳞癌	74	2.45±0.50	0.899	0.371	1.28±0.22	0.520	0.605
腺癌	17	2.33±0.55			1.25±0.20
肿瘤直径
≥3 cm	49	2.51±0.48	1.646	0.103	1.24±0.23	1.088	0.280
＜3 cm	42	2.34±0.53			1.30±0.20
分化程度
低分化	34	2.52±0.42	1.335	0.185	1.23±0.23	1.250	0.214
中高分化	57	2.38±0.55			1.29±0.20
FIGO分期
Ⅰ~Ⅱ期	52	2.26±0.51	3.935	＜0.001	1.34±0.19	3.693	＜0.001
Ⅲ~Ⅳ期	39	2.65±0.42			1.18±0.21
间质浸润深度
≥2/3	43	2.57±0.43	3.145	0.002	1.24±0.22	2.844	0.006
＜2/3	48	2.31±0.54			1.30±0.21
淋巴结转移
有	33	2.70±0.48	4.118	＜0.001	1.16±0.22	4.172	＜0.001
无	58	2.28±0.47			1.34±0.18

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表 3 血清miR-18a、miR-485-5p表达对HPV阳性宫颈癌的诊断价值

Table 3. Diagnostic value of serum miR-18a and miR-485-5p expression in HPV positive cervical cancer

指标	AUC (95% CI)	约登指数	截断值	灵敏度 (%)	特异度 (%)
miR-18a	0.752(0.676~0.818)	0.445	2.26	67.03	77.42
miR-485-5p	0.802(0.730~0.862)	0.500	1.40	75.82	74.19
联合	0.876(0.814~0.924)	0.674		83.52	83.87

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参考文献(26)

[1]	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
[2]	王光演, 谷杭芝, 林风, 等. 夫妻配偶双方生殖器人乳头瘤病毒感染情况分析[J]. 中华全科医学, 2020, 18(10): 1691-1694. doi: 10.16766/j.cnki.issn.1674-4152.001595 WANG G Y, GU H Z, LIN F, et al. The analysis of HPV infection of genitals among heterosexual couples[J]. Chinese Journal of General Practice, 2020, 18(10): 1691-1694. doi: 10.16766/j.cnki.issn.1674-4152.001595
[3]	ALI SYEDA Z, LANGDEN S S S, MUNKHZUL C, et al. Regulatory mechanism of microRNA expression in cancer[J]. Int J Mol Sci, 2020, 21(5): 1723. doi: 10.3390/ijms21051723
[4]	LIU Q Y, GAO L Y, XU L, et al. CASC2 inhibits the growth, migration, and invasion of thyroid cancer cells through sponging miR-18a-5p/FIH1 axis[J]. Kaohsiung J Med Sci, 2021, 37(4): 268-275. doi: 10.1002/kjm2.12331
[5]	ZHAO Y, ZHANG Q, LIU H T, et al. lncRNA PART1, manipulated by transcriptional factor FOXP2, suppresses proliferation and invasion in ESCC by regulating the miR-18a-5p/SOX6 signaling axis[J]. Oncol Rep, 2021, 45(3): 1118-1132. doi: 10.3892/or.2021.7931
[6]	廖迎锋. lncRNA RHPN1-AS1靶向miR-485-5p调控骨肉瘤细胞增殖、凋亡、迁移、侵袭及其分子机制[J]. 现代肿瘤医学, 2021, 29(20): 3544-3552. doi: 10.3969/j.issn.1672-4992.2021.20.007 LIAO Y F. lncRNA RHPN1-AS1 regulates the proliferation, apoptosis, migration and invasion of osteosarcoma cells by targeting miR-485-5p and its molecular mechanism[J]. Journal of Modern Oncology, 2021, 29(20): 3544-3552. doi: 10.3969/j.issn.1672-4992.2021.20.007
[7]	GU J F, DONG L, WANG Y, et al. LINC01224 promotes colorectal cancer progression through targeting miR-485-5p/MYO6 axis[J]. World J Surg Oncol, 2021, 19(1): 281. doi: 10.1186/s12957-021-02389-x
[8]	刘玲, 王静, 肖红尼, 等. miR-18a通过靶向SOX6调控宫颈癌细胞C-33A增殖、凋亡的研究[J/OL]. 中国现代医学杂志, 2021. [2021-10-17]. http://kns.cnki.net/kcms/detail/43.1225.R.20210915.1129.002.html. LIU L, WANG J, XIAO H N, et al. Regulation of proliferation and apoptosis of cervical cancer cells C-33A by miR-18a targeting SOX6[J/OL]. China Journal of Modern Medicine, 2021. [2021-10-17]. http://kns.cnki.net/kcms/detail/43.1225.R.20210915.1129.002.html.
[9]	ZHAO D Y, ZHANG H, LONG J X, et al. LncRNA SNHG7 functions as an oncogene in cervical cancer by sponging miR-485-5p to modulate JUND expression[J]. Onco Targets Ther, 2020, 13: 1677-1689. doi: 10.2147/OTT.S237802
[10]	中国抗癌协会妇科肿瘤专业委员会. 宫颈癌诊断与治疗指南(第四版)[J]. 中国实用妇科与产科杂志, 2018, 34(6): 613-622. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF201806011.htm Chinese Anti-Cancer Association Gynecological Tumor Professional Committee. Guidelines to the diagnosis and treatment of cervical cancer (4th edition)[J]. Chinese Journal of Practical Gynecology and Obstetrics, 2018, 34(6): 613-622. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF201806011.htm
[11]	中华医学会妇科肿瘤学分会, 中国优生科学协会阴道镜和宫颈病理学分会. 人乳头瘤病毒疫苗临床应用中国专家共识[J]. 协和医学杂志, 2021, 12(2): 189-201. https://www.cnki.com.cn/Article/CJFDTOTAL-FKLC202102048.htm Gynecological Oncology Society of Chinese Medical Association, Chinese Society for Colposcopy and Cervical Pathology. Chinese Expert Consensus on Clinical Application of Human Papilloma Virus Vaccine[J]. Medical Journal of Peking Union Medical College Hospital, 2021, 12(2): 189-201. https://www.cnki.com.cn/Article/CJFDTOTAL-FKLC202102048.htm
[12]	World Health Organization. Human papillomavirus vaccines: WHO position paper, May 2017-Recommendations[J]. Vaccine, 2017, 35(43): 5753-5755. doi: 10.1016/j.vaccine.2017.05.069
[13]	中华预防医学会疫苗与免疫分会. 子宫颈癌等人乳头瘤病毒相关疾病免疫预防专家共识[J]. 中华预防医学杂志, 2019, 53(8): 761-803. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201906023.htm Vaccine and Immunization Branch of Chinese Preventive Medicine Association. xpert consensus on immunological prevention of human papillomavirus-related diseases[J]. Chinese Journal of Preventive Medicine, 2019, 53(8): 761-803. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGJM201906023.htm
[14]	GALKA-MARCINIAK P, URBANEK-TRZECIAK M O, NAWROCKA P M, et al. A pan-cancer atlas of somatic mutations in miRNA biogenesis genes[J]. Nucleic Acids Res, 2021, 49(2): 601-620. doi: 10.1093/nar/gkaa1223
[15]	LIU H, ZHANG L, DING X L, et al. LINC00861 inhibits the progression of cervical cancer cells by functioning as a ceRNA for miR-513b-5p and regulating the PTEN/AKT/mTOR signaling pathway[J]. Mol Med Rep, 2021, 23(1): 24.
[16]	YUAN Y Y, SHI X Q, LI B J, et al. Integrated analysis of key microRNAs /TFs /mRNAs/ in HPV-positive cervical cancer based on microRNA sequencing and bioinformatics analysis[J]. Pathol Res Pract, 2020, 216(6): 152952. DOI: 10.1016/j.prp.2020.152952.
[17]	ZHANG J R, WANG L, JIANG J, et al. The lncRNA SNHG15/miR-18a-5p axis promotes cell proliferation in ovarian cancer through activating Akt/mTOR signaling pathway[J]. J Cell Biochem, 2020, 121(12): 4699-4710. doi: 10.1002/jcb.29474
[18]	WEI M F, GU Z S, ZHENG L L, et al. Long non-coding RNA GAS5 promotes natural killer cell cytotoxicity against gastric cancer by regulating miR-18a[J]. Neoplasma, 2020, 67(5): 1085-1093.
[19]	HE C B, MAO D G, HUA G H, et al. The Hippo/YAP pathway interacts with EGFR signaling and HPV oncoproteins to regulate cervical cancer progression[J]. EMBO Mol Med, 2015, 7(11): 1426-1449.
[20]	MATARRESE P, VONA R, ASCIONE B, et al. Physical interaction between HPV16E7 and the actin-binding protein gelsolin regulates epithelial-mesenchymal transition via HIPPO-YAP axis[J]. Cancers (Basel), 2021, 13(2): 353.
[21]	MORGAN E L, PATTERSON M R, RYDER E L, et al. MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer[J]. PLoS Pathog, 2020, 16(6): e1008624. DOI: 10.1371/journal.ppat.1008624.
[22]	朱银川, 王丰云, 杨雁华, 等. 干扰LINC00265上调miR-485-5p的表达影响缺氧诱导的心肌细胞凋亡、增殖机制研究[J]. 中国循证心血管医学杂志, 2021, 13(3): 362-365. https://www.cnki.com.cn/Article/CJFDTOTAL-PZXX202103026.htm ZHU Y C, WANG F Y, YANG Y H, et al. Interfering with LINC00265 can affect apoptosis and proliferation of cardiomyocyte induced by hypoxia through up-regulating the expression of miR-485-5p[J]. Chinese Journal of Evidence-Based Cardiovascular Medicine, 2021, 13(3): 362-365. https://www.cnki.com.cn/Article/CJFDTOTAL-PZXX202103026.htm
[23]	YU J, CHEN X G, LI J, et al. CircRUNX1 functions as an oncogene in colorectal cancer by regulating circRUNX1/miR-485-5p/SLC38A1 axis[J]. Eur J Clin Invest, 2021, 51(7): e13540. DOI: 10.1111/eci.13540.
[24]	CHENG L, PENG R J, GUO P, et al. A HIF1A/miR-485-5p/SRPK1 axis modulates the aggressiveness of glioma cells upon hypoxia[J]. Exp Cell Res, 2021, 402(1): 112547. DOI: 10.1016/j.yexcr.2021.112547.
[25]	GAUTHIER-ROUVIÈRE C, BODIN S, COMUNALE F, et al. Flotillin membrane domains in cancer[J]. Cancer Metastasis Rev, 2020, 39(2): 361-374.
[26]	DAI Y Y, XIE F Y, CHEN Y. Reduced levels of miR-485-5p in HPV-infected cervical cancer promote cell proliferation and enhance invasion ability[J]. FEBS Open Bio, 2020, 10(7): 1348-1361.