Relationship of serum miRNA-196a and miRNA-92a expression levels with recurrence of cervical cancer after radical surgery
WANG Yucun1 HU Tuoyang1 CUI Jing1 HAN Ping2 DING Yan1
1.The Second Department of Gynecology and Oncology, Gansu Provincial Cancer Hospital, Gansu Province, Lanzhou 730050, China;
2.Department of Radiology, Gansu Provincial Cancer Hospital, Gansu Province, Lanzhou 730050, China
Abstract:Objective To investigate the relationship between the expression levels of serum microRNA (miRNA)-196a and miRNA-92a and recurrence of cervical cancer after radical surgery. Methods A total of 113 patients undergoing radical resection of cervical cancer who were admitted to Gansu Provincial Cancer Hospital from January 2015 to June 2016 were selected as the cervical cancer group, qRT-PCR was used to detect serum miRNA-196a and miRNA-92a levels in the both groups. The relationship between serum miRNA-196a and miRNA-92a levels and clinicopathological characteristics of cervical cancer patients was analyzed. Post-operative follow-up for five years, and the cervical cancer patients were divided into high expression and low expression according to the mean value of serum miRNA-196a and miRNA-92a. The recurrence rates of cervical cancer patients in high expression and low expression were compared, multivariate Cox regression was used to analyze the influencing factors of cervical cancer after radical surgery. Receiver operator characteristic (ROC) curve was used to analyze the predictive value of serum miRNA-196a and miRNA-92a levels on recurrence of cervical cancer after radical surgery. Results The expression levels of serum miRNA-196a and miRNA-92a in cervical cancer group were higher than those in control group, and the differences were statistically significant (P < 0.05). There were statistically significant differences in serum miRNA-196a and miRNA-92a levels among cervical cancer patients with different Federation of Gynecology and Obstetrics (FIGO) stages, interstitial invasion depth, and lymph node metastasis (P < 0.05). By the last follow-up, 25 patients (22.12%) of 113 cervical cancer patients had recurrence after surgery and the recurrence rate of miRNA-196a and miRNA-92a of the high expression were higher than those of the low expression, and the differences were statistically significant (P < 0.05). FIGO stage ⅡA, interstitial invasion depth ≥1/2, lymph node metastasis, miRNA-196a ≥5.239, and miRNA-92a ≥1.816 were the independent risk factors for recurrence on cervical cancer after radical surgery (HR > 1, P < 0.05). ROC curve showed that the area under the curve of miRNA-196a combined with miRNA-92a in predicting the recurrence on cervical cancer after radical surgery was greater than that of both alone (Z = 2.319, 2.582, P = 0.020, 0.010). Conclusion Serum miRNA-196a and miRNA-92a levels in cervical cancer are high expression, both of which are associated with FIGO stage, depth of interstitial infiltration, lymph node metastasis, and recurrence, and can be used as predictors of recurrence on cervical cancer after radical surgery.
王雨村1 胡拓阳1 崔静1 韩萍2 丁燕1. 血清miRNA-196a、miRNA-92a表达水平与宫颈癌根治术后复发的关系[J]. 中国医药导报, 2022, 19(17): 27-31.
WANG Yucun1 HU Tuoyang1 CUI Jing1 HAN Ping2 DING Yan1. Relationship of serum miRNA-196a and miRNA-92a expression levels with recurrence of cervical cancer after radical surgery. 中国医药导报, 2022, 19(17): 27-31.
[1] 中华人民共和国国家卫生健康委员会.宫颈癌诊疗规范(2018年版)[J].肿瘤综合治疗电子杂志,2020,6(3):33-43.
[2] Sung H,Ferlay J,Siegel RL,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] Koh WJ,Abu-Rustum NR,Bean S,et al. Cervical Cancer,Version 3.2019,NCCN Clinical Practice Guidelines in Oncology [J]. J Natl Compr Canc Netw,2019,17(1):64-84.
[4] Khan AQ,Ahmed EI,Elareer NR,et al. Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies [J]. Cells,2019,8(8):840.
[5] 王宝军,周爱萍,周红.长链非编码RNA GAS5调控miR-196a抑制胃癌细胞增殖、诱导凋亡及放射增敏的机制[J].中国老年学杂志,2021,41(4):853-857.
[6] Xin H,Wang C,Liu Z. miR-196a-5p promotes metastasis of colorectal cancer via targeting IκBα [J]. BMC Cancer,2019,19(1):30.
[7] 胡爱妮,王豫萍,路毅斌,等.miR-92a靶向PTEN/PI3K/Akt通路抑制非小细胞肺癌细胞的自噬[J].第三军医大学学报,2020,42(13):1301-1307.
[8] 单留群,方征,刘洪,等.miR-92a通过下调RAB3B表达促进肝癌细胞增殖、迁移的机制分析[J].临床和实验医学杂志,2019,18(12):1266-1270.
[9] Lee SI,Atri M. 2018 FIGO Staging System for Uterine Cervical Cancer:Enter Cross-sectional Imaging [J]. Radiology,2019,292(1):15-24.
[10] H?觟ckel M,Wolf B,Schmidt K,et al. Surgical resection based on ontogenetic cancer field theory for cervical cancer:mature results from a single-centre,prospective,observational,cohort study [J]. Lancet Oncol,2019,20(9):1316-1326.
[11] 郑楹楹,吕宏英,陈正飞,等.宫颈癌根治术后患者康复期症状体验及心理感受的质性研究[J].中华护理杂志,2020,55(4):569-573.
[12] Nahand JS,Taghizadeh-Boroujeni S,Karimzadeh M,et al. microRNAs:New prognostic,diagnostic,and therapeutic biomarkers in cervical cancer [J]. J Cell Physiol,2019, 234(10):17064-17099.
[13] Yang Y,Liu Y,Liu W,et al. miR-122 Inhibits the Cervical Cancer Development by Targeting the Oncogene RAD21 [J]. Biochem Genet,2022,60(1):303-314.
[14] Yang W,Wang X,Song S,et al. Long noncoding RNA ALOX12-AS1 inhibits cervical cancer cells proliferation via targeting miR-3171 [J]. Anticancer Drugs,2022,33(1):e362-e369.
[15] Yang S,Sun Y,Jiang D,et al. MiR-362 suppresses cervical cancer progression via directly targeting BAP31 and activating TGFβ/Smad pathway [J]. Cancer Med,2021,10(1):305-316.
[16] Liu H,Zhang L,Ding X,et al. LINC00861 inhibits the progression of cervical cancer cells by functioning as a ceRNA for miR513b5p and regulating the PTEN/AKT/mTOR signaling pathway [J]. Mol Med Rep,2021,23(1):24.
[17] Lee S,Hong JH,Kim JS,et al. Cancer-associated fibroblasts activated by miR-196a promote the migration and invasion of lung cancer cells [J]. Cancer Lett,2021,508:92-103.
[18] Takkar S,Sharma V,Ghosh S,et al. Hypoxia-inducible miR-196a modulates glioblastoma cell proliferation and migration through complex regulation of NRAS [J]. Cell Oncol(Dordr),2021,44(2):433-451.
[19] 梁燕,朱万娇,张志苏,等.miR-196a通过靶向NR6A1降低宫颈癌Hela细胞生存和运动能力[J].局解手术学杂志,2021,30(2):93-99.
[20] Qiu YF,Han Q,Lu H,et al. miR-196a targeting LRIG3 promotes the proliferation and migration of cervical cancer cells [J]. Cell Mol Biol(Noisy-le-grand),2020,66(7):180-185.
[21] Hang JH,Zhou QH,Chen CC,et al. MicroRNA miR-92a-3p regulates breast cancer cell proliferation and metastasis via regulating B-cell translocation gene 2(BTG2)[J]. Bioengineered,2021,12(1):2033-2044.
[22] 王万里,郭淑利,王慧睿.微小RNA-92a靶向FHIT基因调控淋巴瘤细胞增殖及凋亡的机制研究[J].中华生物医学工程杂志,2019,25(2):177-182.
[23] 王利娟,谷丽娟,孙颖川.miR-92a对宫颈癌细胞增殖凋亡影响及其机制[J].青岛大学学报(医学版),2019, 55(4):406-410.
[24] Vallejo-Díaz J,Chagoyen M,Olazabal-Morán M,et al. The Opposing Roles of PIK3R1/p85α and PIK3R2/p85β in Cancer [J]. Trends Cancer,2019,5(4):233-244.
[25] Wang Y,Chen A,Zheng C,et al. miR-92a promotes cervical cancer cell proliferation,invasion,and migration by directly targeting PIK3R1 [J]. J Clin Lab Anal,2021,3(2021):e23893.