METTL3在早期鳞状细胞宫颈癌中的表达及其与临床特征和预后的关系

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1299 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探讨甲基化转移酶3(METTL3)在早期鳞状细胞宫颈癌中的表达及其与临床特征和预后的关系。方法纳入2008年1－12月行广泛性子宫切除术治疗的110例早期宫颈癌石蜡组织标本。采用免疫组织化学检测肿瘤标本和癌旁非肿瘤宫颈组织中METTL3的表达,将患者分为METTL3高表达及低表达组,使用Kaplan-Meier生存分析法明确METTL3表达水平与预后的关系,使用Cox比例风险回归分析早期宫颈癌患者预后不良的影响因素。结果宫颈癌肿瘤组织METTL3表达水平(2.705±0.273)明显低于正常宫颈标本(8.574±0.421),差异有统计学意义(P<0.01)。METTL3低表达与较高的FIGO分期(P=0.041)、盆腔淋巴结转移(P=0.001)相关。Kaplan-Meier生存分析表明METTL3低表达有低的总生存率(HR=3.576,95% CI:1.474~8.677,P=0.0048)。Cox多因素分析表明,FIGO分期(HR=5.109, 95% CI: 1.891~11.135, P<0.01)、盆腔淋巴结转移(HR=2.395, 95% CI:1.156~4.879, P=0.017)及METTL3低表达(HR=6.187, 95% CI:2.314~21.292, P=0.004)是早期宫颈癌患者的独立预后因素。结论 METTL3 表达水平在宫颈癌组织中明显下降,FIGO分期、盆腔淋巴结转移及METTL3 表达水平是早期鳞状细胞宫颈癌患者预后不良的影响因素。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	王彩霞
	卢寒
	周宏
	帅翰林
	李玉洁

关键词 ：宫颈癌, 甲基化转移酶3, 预后, 生存分析

Abstract：Objective To investigate the relationship between the expression of METTL3 and its clinical features and prognosis in early-stage squamous cell cervical cancer.Methods This study included paraffin samples from 110 patients with cervical cancer who underwent radical hysterectomy from January 2008 to December 2008. Immunohistochemistry was used to detect the METTL 3 expression in tumor specimens and non-tumor cervical tissues, and patients were divided into high-expression group and low-expression group. Kaplan-Meier survival analysis was used to determine the relationship between the expression level of METTL 3 and prognosis. Cox proportional hazard regression analysis was used to analyze the influencing factors of poor prognosis of early cervical cancer patients.Results The expression level of METTL3 in tumor tissues of patients with cervical cancer was significantly lower than that in normal cervical specimens (P<0.01). Low METTL3 expression was associated with higher FIGO staging (P=0.041) and pelvic lymph node metastasis (P=0.001). Kaplan-Meier survival analysis showed that low METTL3 expression was associated with worse overall survival (HR=3.576, 95%CI=1.474-8.677, P=0.0048). Cox multivariate analysis showed that FIGO installment (HR=5.109, 95% CI: 1.891-11.135, P<0.01), pelvic metastases (HR=2.395, 95 % CI: 1.156-4.879, P<0.05),and low expression of METTL3(HR=6.187, 95% CI: 2.314-21.292, P=0.004) were the independent prognostic factor in patients with early cervical cancer.Conclusion METTL3 expression level has decreased significantly in cervical cancer tissue. The FIGO staging, pelvic lymph node metastasis and METTL3 expression levels are independent indicators for poor prognosis of patients with early squamous cell cervical cancer.

Key words： cervical cancer METTL3 prognosis survival analysis

收稿日期: 2022-03-10

ZTFLH:

R737.33

基金资助:广东省自然科学基金(2021A1515011221)

通讯作者: 帅翰林,E-mail:piaoshuai2003@126.com

作者简介: 王彩霞,硕士,副主任医师。

引用本文:

王彩霞, 卢寒, 周宏, 帅翰林, 李玉洁. METTL3在早期鳞状细胞宫颈癌中的表达及其与临床特征和预后的关系[J]. 武警医学, 2022, 33(8): 645-649. WANG Caixia, LU Han, ZHOU Hong, SHUAI Hanlin, LI Yujie. Analysis of relationship between the expression of METTL3 and its clinical features and prognosis in early-stage squamous cell cervical cancer. Med. J. Chin. Peop. Armed Poli. Forc., 2022, 33(8): 645-649.

链接本文:

http://journal08.magtechjournal.com/Jwk_wjyx/CN/ 或 http://journal08.magtechjournal.com/Jwk_wjyx/CN/Y2022/V33/I8/645

[1]	Jemal A, Bray F, Center M M, et al. Global cancer statistics [J]. CA Cancer J Clin, 2011, 61(2): 69-90.
[2]	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.
[3]	Cohen A C, Roane B M, Leath C A 3rd. Novel therapeutics for recurrent cervical cancer: moving towards personalized therapy [J]. Drugs, 2020, 80(3): 217-227.
[4]	Tsikouras P, Zervoudis S, Manav B, et al. Cervical cancer: screening, diagnosis and staging [J]. J Buon, 2016, 21(2): 320-325.
[5]	Lan Q, Liu P Y, Haase J, et al. The critical role of rna m6A methylation in cancer [J]. Cancer Res, 2019, 79(7): 1285-1292.
[6]	Maity A, Das B. N6-methyladenosine modification in mrna: Machinery, function and implications for health and diseases [J]. Febs J, 2016, 283(9): 1607-1630.
[7]	Li F, Wang H, Huang H, et al. M6a RNA methylation regulators participate in the malignant progression and have clinical prognostic value in lung adenocarcinoma [J]. Front Genet, 2020, 11: 994.
[8]	Wang H, Xu B, Shi J. N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2 [J]. Gene, 2020, 722: 144076.
[9]	Bhatla N, Berek J S, Cuello Fredes M, et al. Revised figo staging for carcinoma of the cervix uteri [J]. Int J Gynaecol Obstet, 2019, 145(1): 129-135.
[10]	Luo J, Liu H, Luan S, et al. Aberrant regulation of mrna m6A modification in cancer development [J]. Int J Mol Sci, 2018, 19(9): 1011-1023.
[11]	Ma S, Chen C, Ji X, et al. The interplay between m6A RNA methylation and noncoding RNA in cancer [J]. J Hematol Oncol, 2019, 12(1): 121.
[12]	He L, Li H, Wu A, et al. Functions of n6-methyladenosine and its role in cancer [J]. Mol Cancer, 2019, 18(1): 176.
[13]	赵敬, 杨金豪, 常艳敏, 等. 中国宫颈癌DNA甲基化标志物的研究进展[J]. 天津医科大学学报, 2021, 27(5): 545-548.
[14]	Chen M, Wei L, Law C T, et al. RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SCOS2 [J]. Hepatology, 2018, 67(6): 2254-2270.
[15]	Roundtree I A, Evans M E, Pan T, et al. Dynamic RNA modifications in gene expression regulation [J]. Cell, 2017, 169(7): 1187-1200.
[16]	Han J, Wang J Z, Yang X, et al. METTL3 promote tumor proliferation of bladder cancer by accelerating pri-mir221/222 maturation in m6a-dependent manner [J]. Mol Cancer, 2019, 18(1): 110.
[17]	Cheng M, Sheng L, Gao Q, et al. The m(6)a methyltransferase METTL3 promotes bladder cancer progression via AFF4/nf-κb/myc signaling network [J]. Oncogene, 2019, 38(19): 3667-3680.
[18]	Vu L P, Pickering B F, Cheng Y, et al. The n(6)-methyladenosine (m(6)a)-forming enzyme METTL3 controls myeloid differentiation of normal hematopoietic and leukemia cells [J]. Nat Med, 2017, 23(11): 1369-1376.
[19]	Wu R, Guo G, Bi Z, et al. M(6)a methylation modulates adipogenesis through JAK2-stat3-c/ebpβ signaling [J]. Biochim Biophys Acta Gene Regul Mech, 2019, 1862(8): 796-806.
[20]	Chen X Y, Zhang J, Zhu J S. The role of m(6)a RNA methylation in human cancer [J]. Mol Cancer, 2019, 18(1): 103.
[21]	Pan F, Lin X R, Hao L P, et al. The role of RNA methyltransferase METTL3 in hepatocellular carcinoma: results and perspectives [J]. Front Cell Dev Biol, 2021, 9: 674919.
[22]	Lin S, Liu J, Jiang W, et al. METTL3 promotes the proliferation and mobility of gastric cancer cells [J]. Open Med (Wars), 2019, 14: 25-31.
[23]	Shi Y, Zheng C, Jin Y, et al. Reduced expression of METTL3 promotes metastasis of triple-negative breast cancer by m6A methylation-mediated COL3A1 up-regulation [J]. Front Oncol, 2020, 10: 1126.
[24]	Xu J, Chen Q, Tian K, et al. M6a methyltransferase METTL3 maintains colon cancer tumorigenicity by suppressing SOCS2 to promote cell proliferation [J]. Oncol Rep, 2020, 44(3): 973-986.
[25]	Xia T L, Yan S M, Yuan L, et al. Upregulation of METTL3 expression predicts poor prognosis in patients with esophageal squamous cell carcinoma [J]. Cancer Manag Res, 2020, 12: 5729-5737.
[26]	Wang W, Shao F, Yang X, et al. METTL3 promotes tumour development by decreasing apc expression mediated by apc mRNA n(6)-methyladenosine-dependent ythdf binding[J]. Nat Commun, 2021, 12(1): 3803.
[27]	Ni H H, Zhang L, Huang H, et al. Connecting METTL3 and intratumoural CD33(+) mdscs in predicting clinical outcome in cervical cancer [J]. J Transl Med, 2020, 18(1): 393.
[28]	Hu Y, Li Y, Huang Y, et al. METTL3 regulates the malignancy of cervical cancer via post-transcriptional regulation of RAB2B [J]. Eur J Pharmacol, 2020, 879: 173134.