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北京大学学报（医学版） ›› 2020, Vol. 52 ›› Issue (3): 570-577. doi: 10.19723/j.issn.1671-167X.2020.03.026

• 论著 • 上一篇    下一篇

144例维吾尔族与汉族女性子宫内膜癌微小RNA表达特点及临床意义

王晓1,贺丹1,李文婷2,阿迪拉·斯依提2,韩蕊1,董颖1,△()   

  1. 1. 北京大学第一医院病理科, 北京 100034
    2. 新疆医科大学附属肿瘤医院病理科, 乌鲁木齐 830011
  • 收稿日期:2018-04-02 出版日期:2020-06-18 发布日期:2020-06-30
  • 通讯作者: 董颖 E-mail:dongying_999@163.com
  • 基金资助:
    国家自然科学基金(81360381)

Characteristic and clinical significance of microRNA expression between 144 Uygur and Han women with endometrial carcinoma

Xiao WANG1,Dan HE1,Wen-ting LI2,SIYITI Adila·2,Rui HAN1,Ying DONG1,△()   

  1. 1. Department of Pathology, Peking University First Hospital, Beijing 100034, China
    2. Department of Pathology, Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi 830011, China
  • Received:2018-04-02 Online:2020-06-18 Published:2020-06-30
  • Contact: Ying DONG E-mail:dongying_999@163.com
  • Supported by:
    National Natural Science Foundation of China(81360381)

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摘要：

目的 分析144例女性子宫内膜癌微小RNA(microRNA,miRNA)的表达特点,对比其在维吾尔族与汉族女性子宫内膜癌中的表达差异及其与临床病理特点的内在关联性,阐述临床意义。方法 144例维吾尔族与汉族女性(包括62例维吾尔族和82例汉族),采用Taqman低密度芯片对比两者子宫内膜癌miRNA的表达特点,选取5种miRNA,采用实时定量PCR法验证并分析这些miRNA的表达特点。结果 miRNA表达谱分析显示,Ⅱ型癌突出的特点是许多miRNA在一个民族中表达升高或降低,而在另一个民族中不表达或变化轻微。144例女性的子宫内膜癌miR-141、miR-200a、miR-205表达均升高,维吾尔族女性Ⅰ型癌miR-141/200a表达升高的肿瘤更具侵袭性,而汉族女性Ⅰ型癌的特点相反,miR-200a表达升高的肿瘤侵袭性呈减弱趋势,但Ⅱ型癌miR-200a表达升高的肿瘤趋向更具侵袭性。miR-145、miR-143在维吾尔族与汉族女性子宫内膜癌中的表达特点相反,在维吾尔族表达升高,在汉族显著降低(P<0.05)。维吾尔族中Ⅱ型癌miR-145、miR-143升高更明显,侵袭性相对弱的肿瘤的miR-145表达水平更高,肌层浸润深度<1/2组差异有统计学意义(P=0.042)。汉族女性Ⅰ/Ⅱ型癌中miR-145和miR-143的表达均降低,侵袭性强的Ⅰ型癌中两者降低得更明显,但差异无统计学意义;Ⅱ型癌不具此特点。结论 维吾尔族与汉族女性子宫内膜癌miRNA表达存在一定差异性,miR-141/200a/205在子宫内膜癌中普遍表达升高,但miR-141/200a在维吾尔族与汉族Ⅰ/Ⅱ型子宫内膜癌中扮演的角色可能不尽相同。miR-145/143在维吾尔族与汉族女性子宫内膜癌中的表达特点相反,但可能均发挥抑癌作用。

关键词: 子宫内膜癌, 癌, 子宫内膜样, 微RNAs

Abstract:

Objective: To compare the expression patterns of microRNA (miRNA) between 144 Uygur and Han women with endometrial carcinoma and to investigate their clinical significance.Methods: Taqman miRNA low-density array was used to compare miRNA profiles between Uygur and Han women with non-endometrioid endometrial carcinoma (NEEC). Five miRNAs were further analyzed in the 144 endometrial cancers including 62 Uygur and 82 Han samples via real-time PCR to determine their expression patterns.Results: MiRNA expression profiles revealed that many miRNAs overexpressed or downregula-ted in one ethnic group, but did not express or changed slightly in the other ethnic group. Further detection in the 144 endometrial cancers showed that miR-141, miR-200a, and miR-205 overexpressed in both ethnic groups. In Uygur endometrioid endometrial carcinoma (EEC), tumors with miR-141/200a overexpression tended to be more aggressive in behavior, whereas in the Han group, EEC with miR-200a overexpression was relative mild. However, the NEEC with miR-200a overexpression also had aggressive clinicopathologic features in the Han women. MiR-145 and miR-143 expressed differentially between Uygur and Han groups, they overexpressed in the former and decreased in the latter (P<0.05). In the Uygur women miR-145/143 increased significantly in NEEC and there was a trend that NEEC exhibiting favorable clinicopathologic factors had higher miR-145 expression, and was statistically significant in tumors with myometrial invasion less than 1/2 thickness (P=0.042). By contrary, miR-145/143 decreased in Han group and EEC with worse clinicopathologic variables had lower expression although without statistical significance. NEEC in Han group had no such tendency.Conclusion: Uygur and Han women might have different miRNA expression profiles. MiR-141/200a/205 overexpressed in endometrial carcinomas and miR-141/200a might behave differently between these two ethnic groups as well as in EEC and in NEEC. Although miR-145/143 showed inverse expression patterns between Uygur and Han women with endometrial cancer, they all exerted tumor suppression effect on endometrial cancer.

Key words: Endometrial carcinoma, Carcinoma, endometrioid, MicroRNAs

中图分类号: 

  • R737.33

表1

维吾尔族与汉族Ⅱ型子宫内膜癌中表达差异的miRNAs"

miRNA log2 (relative quantity)
Uygur Han
hsa-miR-101#-002143 0.071 15.513
hsa-miR-876-3p-4395336 0.053 10.105
hsa-miR-299-5p-4373188 0.037 87.624
hsa-miR-885-5p-4395407 0.019 47.159
hsa-miR-218-2#-002294 0.012 32.331
hsa-let-7c#-002405 0.012 526.021
hsa-miR-450b-5p-4395318 0.003 334.49
hsa-miR-876-5p-4395316 0.003 334.728
hsa-miR-643-001594 0.003 516.767
hsa-miR-497#-002368 0.001 265.121
hsa-miR-29b-1#-002165 0.001 295.243
hsa-miR-504-4395195 0 363.642
hsa-miR-296-3p-4395212 0 2 683.919
hsa-miR-941-002183 0 4 023.437
hsa-miR-1267-002885 94 877.297 0
hsa-miR-486-3p-4395204 14 529.595 0
hsa-miR-654-5p-4381014 3 411.37 0.001
hsa-miR-541-4395312 3 315.935 0
hsa-miR-431-4395173 3 306.269 0.001
hsa-miR-486-5p-4378096 1 747.636 0.075
hsa-miR-452#-002330 169.787 0.004
hsa-miR-548J-002783 85.613 0.004
hsa-miR-523-4395497 19.512 0.049

图1

miR-141、miR-200a、miR-205、miR-143和miR-145在维吾尔族和汉族患者中的表达"

表2

miR-141、miR-200a、miR-205、miR-143、miR-145在维吾尔族女性EEC (n=49)和NEEC (n=13)中的表达"

Variable log2 (relative quantity),mean±SE
miR-141 miR-200a miR-205 miR-143 miR-145
EEC NEEC EEC NEEC EEC NEEC EEC NEEC EEC NEEC
Histologic type 4.60±0.42 3.65±0.79 5.12±0.42 4.45±0.69 4.44±0.40 4.02±0.69 0.52±0.51 2.04±0.73 1.99±0.56 3.95±0.83
P <0.001 0.003 <0.001 <0.001 <0.001 0.001 0.504 0.040 0.013 <0.001
Age
Premenopause (n=25) 4.69±0.68 3.65±0.24 4.93±0.72 2.44±1.71 4.27±0.75 4.21±0.64 0.52±0.68 1.92±2.04 2.25±0.98 3.54±0.95
Postmenopause (n=37) 4.53±0.55 3.65±1.04 5.28±0.50 5.05±0.68 4.58±0.61 3.97±0.90 0.53±0.75 2.07±0.81 1.79±0.65 4.07±1.06
P 0.854 0.999 0.687 0.115 0.751 0.894 0.991 0.935 0.688 0.801
Grade (EEC)
Low (n=21) 4.33±0.68 - 4.87±0.45 - 4.49±0.78 - 1.08±0.93 - 2.20±0.62 -
High (n=28) 4.81±0.55 - 6.93±0.76 - 4.41±0.59 - 0.10±0.55 - 0.52±1.06 -
P 0.580 0.044 0.934 0.371 0.376
Myometrial invasiona
<1/2 (n=35) 4.17±0.55 1.28±1.77 4.76±0.56 1.53±0.88 3.81±0.61 1.85±1.62 -0.39±0.57 3.90±1.20 1.40±0.76 5.98±1.13
≥1/2 (n=13) 5.72±0.81 4.48±0.66 6.14±0.81 5.53±0.47 4.83±1.73 4.84±0.52 -0.88±0.75 1.11±0.90 0.65±0.99 2.86±1.08
P 0.284 0.167 0.225 0.011 0.547 0.160 0.617 0.099 0.945 0.042
Lymph node metastasesb
No (n=37) 4.35±0.62 4.04±0.71 5.03±0.60 4.53±0.79 3.88±0.74 4.28±0.68 -0.36±0.63 2.46±0.90 1.61±0.87 4.08±1.07
Yes (n=4) 5.40±1.07 3.44 5.69±1.09 3.26 3.98±1.82 4.63 -0.80±0.47 -0.56 0.51±0.74 1.86
P 0.590 0.807 0.704 0.343 0.964 0.879 0.588 0.337 0.809 0.527
Vessel invasiona
No (n=38) 4.36±0.54 3.00±1.17 4.86±0.54 3.66±1.04 3.96±0.62 3.65±0.85 -0.58±0.54 2.11±1.27 1.24±0.75 3.92±1.05
Yes (n=10) 4.55±1.40 3.97±1.21 5.53±1.26 4.94±0.85 3.90±1.61 4.11±1.41 0.30±1.30 1.95±0.90 1.62±1.23 3.88±1.73
P 0.900 0.586 0.909 0.465 0.970 0.771 0.547 0.924 0.450 0.935
Stagea
Ⅰ or Ⅱ (n=40) 4.30±0.53 3.81±1.21 4.89±0.53 4.21±1.12 3.95±0.61 3.47±0.85 -0.43±0.54 1.47±1.03 1.37±0.72 4.57±2.06
Ⅲ or Ⅳ (n=8) 5.40±1.07 2.85±1.11 5.69±1.09 4.16±0.76 3.98±1.82 4.37±1.37 -0.80±0.47 2.84±1.30 0.51±0.74 3.43±0.66
P 0.546 0.588 0.358 0.194 0.989 0.570 0.617 0.422 0.932 0.570

表3

miR-141、miR-200a、miR-205、miR-143、miR-145在汉族女性EEC (n=53)和NEEC (n=29)中的表达"

Variable log2 (relative quantity), mean±SE
miR-141 miR-200a miR-205 miR-143 miR-145
EEC NEEC EEC NEEC EEC NEEC EEC NEEC EEC NEEC
Histologic type 2.63±0.34 4.82±1.01 2.61±0.38 5.81±1.30 4.51±0.52 4.31±0.79 -2.43±0.34 -0.13±1.16 -2.61±0.32 -2.70±0.92
P 0.023 <0.001 <0.001 <0.001 0.012 0.015 <0.001 0.009 0.001 0.187
Age
Premenopause (n=28) 2.78±0.56 4.79±1.84 1.76±0.70 8.21±1.64 4.97±0.84 5.18±1.55 -2.22±0.53 -2.54±1.34 -1.94±0.53 0.84±2.81
Postmenopause (n=54) 2.55±0.43 4.62±0.98 3.12±0.42 5.03±1.31 4.23±0.67 4.35±0.71 -2.85±0.39 -1.73±0.69 -2.73±0.44 0.01±0.83
P 0.751 0.934 0.082 0.247 0.499 0.606 0.334 0.596 0.267 0.702
Grade (EEC)
Low (n=28) 2.60±0.46 - 2.64±0.42 - 3.89±0.80 - -2.39±0.46 - -2.36±0.37 -
High (n=25) 2.68±0.51 - 2.43±0.86 - 5.20±0.64 - -2.86±0.43 - -2.92±0.80 -
P 0.907 0.694 0.212 0.470 0.446
Myometrial invasiona
<1/2 (n=62) 2.55±0.43 4.62±0.98 2.63±0.41 5.43±1.49 4.67±0.54 4.40±0.71 -2.32±0.35 -2.43±0.82 -2.26±0.36 -0.73±1.33
≥1/2 (n=19) 2.88±0.46 4.31±1.95 2.55±0.81 7.08±3.16 4.06±1.30 3.95±1.56 -3.41±0.66 -1.70±0.85 -2.90±0.83 1.91±2.22
P 0.603 0.876 0.817 0.614 0.609 0.762 0.129 0.609 0.431 0.160
Lymph node metastasesb
No (n=32) 2.72±0.58 5.05±1.20 3.19±0.63 5.70±2.05 4.35±1.12 4.53±0.85 -2.15±0.58 -1.92±0.89 -1.84±0.69 -0.02±1.57
Yes (n=8) 2.29±1.32 5.21±0.90 2.71±1.69 6.36±1.35 4.02±1.13 2.00±1.65 -2.82±0.79 -4.97±1.90 -2.51±1.05 -3.23±1.71
P 0.738 0.956 0.411 0.671 0.879 0.229 0.567 0.172 0.457 0.457
Vessel invasiona
No (n=67) 2.69±0.38 4.47±1.03 2.77±0.38 5.68±1.57 4.48±0.61 4.39±0.78 -2.45±0.36 -2.54±0.76 -2.35±0.37 -0.35±1.44
Yes (n=14) 2.37±0.78 4.78±1.70 1.84±1.25 6.42±2.81 4.65±0.70 3.80±1.19 -3.40±0.62 -0.96±0.67 -2.81±0.88 0.93±0.90
P 0.733 0.891 0.255 0.867 0.906 0.727 0.260 0.322 0.602 0.073
Stagea
Ⅰ or Ⅱ (n=68) 2.63±0.37 3.81±0.99 2.71±0.38 4.53±1.60 4.49±0.59 4.21±0.66 -2.45±0.34 -1.83±0.70 -2.27±0.36 -0.42±1.28
Ⅲ or Ⅳ (n=13) 2.67±0.94 6.97±1.73 1.98±1.53 9.77±1.91 4.64±0.87 4.49±1.96 -3.64±0.77 -3.56±1.38 -3.51±0.97 0.98±2.63
P 0.970 0.134 0.587 0.570 0.925 0.862 0.204 0.252 0.172 0.507

图2

DNMT3B在维吾尔族和汉族女性中的过表达率"

表4

维吾尔族与汉族女性子宫内膜癌中DNMT3B的表达特点"

Variable DNMT3B overexpression
Uygur Han
EEC NEEC EEC NEEC
Histologic type 67.3% (33/49) 84.6% (11/13) 60.4% (32/53) 41.4% (12/29)
P 0.312 0.099
Grade (EEC)
Low 65.1% (28/43) - 58.7% (27/46) -
High 83.3%(5/6) - 71.4% (5/7) -
P 0.690 0.649
Myometrial invasion
<1/2 64.5% (20/31) 50.0% (2/4) 61.5% (24/39) 33.3% (7/21)
≥1/2 100.0% (5/5) 100.0% (8/8) 57.1% (4/7) 57.1% (4/7)
P 0.295 0.091 0.773 0.381
Lymph node metastases
No 66.7% (18/27) 90.0% (9/10) 47.1% (8/17) 57.1% (8/14)
Yes 50.0% (1/2) 100.0% (1/1) 80.0% (4/5) 50.0% (2/4)
P 0.323 >0.999 0.534 >0.999
Vessel invasion
No 66.7% (21/31) 71.4% (5/7) 59.1% (26/44) 40.9% (9/22)
Yes 80.0% (4/5) 100.0% (5/5) 66.7% (6/9) 33.3% (2/6)
P 1.000 0.470 >0.999 >0.999
Stage
Ⅰ or Ⅱ 66.7% (22/33) 71.4% (5/7) 58.1% (27/46) 38.1% (8/21)
Ⅲ or Ⅳ 100.0% (3/3) 100.0% (5/5) 71.4% (5/7) 42.9% (3/7)
P 0.538 0.470 0.690 >0.999
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ISSN 1671-167X
CN 11-4691/R
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