切换至 "中华医学电子期刊资源库"

中华结直肠疾病电子杂志 ›› 2021, Vol. 10 ›› Issue (02) : 132 -136. doi: 10.3877/cma.j.issn.2095-3224.2021.02.004

所属专题: 文献

论著

微卫星不稳定状态与结直肠癌患者临床病理特征的相关性研究
张冬生1, 封益飞1, 王勇1, 胥子玮1, 唐俊伟1, 黄远健1, 张川1, 孙跃明1,()   
  1. 1. 210029 南京医科大学第一附属医院结直肠外科
  • 收稿日期:2020-08-27 出版日期:2021-04-25
  • 通信作者: 孙跃明
  • 基金资助:
    国家重点研发计划(2017YFC0908200(AH17))

Study on the relationship between microsatellite instability status and clinicopathological characteristics of colorectal cancer patients

Dongsheng Zhang1, Yifei Feng1, Yong Wang1, Ziwei Xu1, Junwei Tang1, Yuanjian Huang1, Chuan Zhang1, Yueming Sun1,()   

  1. 1. The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
  • Received:2020-08-27 Published:2021-04-25
  • Corresponding author: Yueming Sun
引用本文:

张冬生, 封益飞, 王勇, 胥子玮, 唐俊伟, 黄远健, 张川, 孙跃明. 微卫星不稳定状态与结直肠癌患者临床病理特征的相关性研究[J/OL]. 中华结直肠疾病电子杂志, 2021, 10(02): 132-136.

Dongsheng Zhang, Yifei Feng, Yong Wang, Ziwei Xu, Junwei Tang, Yuanjian Huang, Chuan Zhang, Yueming Sun. Study on the relationship between microsatellite instability status and clinicopathological characteristics of colorectal cancer patients[J/OL]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2021, 10(02): 132-136.

目的

探究微卫星不稳定(MSI)状态与结直肠癌患者临床病理特征的相关性。

方法

采用回顾性队列研究方法,收集2015年1月至2019年12月南京医科大学第一附属医院结直肠外科1 280例结直肠癌手术患者的临床病理资料,其中男性800例,女性480例;中位年龄为63岁;右半结肠癌337例,左半结肠癌398例,直肠癌545例。PCR方法检测肿瘤标本的微卫星状态。依据MSI状态,将患者分为高度微卫星不稳定性(MSI-H)组和微卫星稳定性(MSS)/低度微卫星不稳定性(MSI-L)组。观察人口学特征,手术标本病理学检查,微卫星状态等指标。计数资料以绝对数或百分比表示,组间比较采用卡方检验或Fisher精确检验。等级资料采用秩和检验。非正态分布资料,采用中位数MP25,P75)表示,组间比较采用曼-惠特尼U检验。

结果

在1 280例患者中,112例(8.7%)为MSI-H,79例(6.2%)为MSI-L,1 089例(85.1%)为MSS。MSI-H组与MSS/MSI-L组患者在术前血清CEA(χ2=6.943,P<0.05)、肿瘤部位(Z=-9.451,P<0.001)、肿瘤TNM分期(Z=-2.108,P<0.05)、肿瘤T分期(Z=-2.397,P<0.05)、肿瘤N分期(Z=-3.892,P<0.001)、肿瘤分化(χ2=6.663,P<0.05)、肿瘤黏液成分(χ2=78.833,P<0.001)、肿瘤最大直径(χ2=39.656,P<0.001)、癌结节(χ2=8.759,P<0.05)、神经侵犯(χ2=10.238,P<0.05)、淋巴结转移率(LNR)(χ2=5.880,P<0.05)、淋巴结检出数(Z=-5.019,P<0.001)、阳性淋巴结检出数(Z=-3.667,P<0.001)等方面差异有统计学意义,主要表现为,MSI-H组患者CEA<4.7 ng/mL、右半结肠癌、低TNM分期、高T分期、低N分期、低分化、黏液成分、肿瘤直径≥4 cm、无癌结节、无神经侵犯、低LNR所占比例显著高于MSS/MSI-L组患者。MSI-H组淋巴结检出数显著多于MSS/MSI-L组,而阳性淋巴结检出数显著较少。

结论

MSI-H结直肠癌患者具有较为特殊的临床病理特征,其中既有预后良好的,亦有预后不良的特征。

Objective

To identify the relationship between microsatellite instability(MSI) status and clinicopathological characteristics of colorectal cancer patients.

Methods

The clinicopathological data of 1 280 colorectal cancer patients from Jan 2015 to Dec 2019 were retrospectively analyzed. These patients had received radical resection for colorectal cancer in the Colorectal Surgery Department of the First Affiliated Hospital of Nanjing Medical University. Among these patients, there were 800 male and 480 female patients. The median age was 63 years (range 26~91 years). There were 337 right colon cancer patients, 398 left colon cancer patients and 545 rectal cancer patients. Microsatellite instability status was detected by polymerase chain reaction. The patients were divided into microsatellite instability high (MSI-H) and microsatellite stable/microsatellite instability low (MSS/MSI-L) groups. Patient characteristics, postoperative pathological examinations, MSI status were collected and analyzed. Count data were described as absolute numbers or percentages. Comparison of count data between groups was analyzed using the chi square test or Fisher's exact test. Rank sum test was used for ranked data. Measurement data with non-normal distribution were described as M (P25, P75), and comparison between groups was done using Mann-Whitney U Test.

Results

Among 1 280 colorectal cancer patients, 112(8.7%) patients were MSI-H, 79(6.2%) were MSI-L, and 1 089(85.1%) were MSS. Distinctive differences were found concerning preoperative blood serum level of CEA (χ2=6.943, P<0.05), tumor localization (Z=-9.451, P<0.001), TNM stage (Z=-2.108, P<0.05), T stage (Z=-2.397, P<0.05), N stage (Z=-3.892, P<0.001), differentiation (χ2=6.663, P<0.05), mucinous differentiation (χ2=78.833, P<0.001), tumor size (χ2=39.656, P<0.001), tumor deposits (χ2=8.759, P<0.05), perineural invasion (χ2=10.238, P<0.05), lymph node metastasis ratio (LNR) (χ2=5.880, P<0.05), lymph node count (Z=-5.019, P<0.001), positive lymph node count (Z=-3.667, P<0.001) between MSI-H and MSS/MSI-L colorectal cancer patients. More patients were found with CEA<4.7 ng/mL, right colon cancer, low TNM stage, high T stage, low N stage, poor differentiation, mucinous differentiation, tumor size ≥4 cm, no tumor deposits, no perineural invasion, low lymph node ratio, high lymph node count and low positive lymph node count in MSI-H patients.

Conclusion

Compared with MSS/MSI-L patients, MSI-H colorectal patients have distinctive clinicopathological features, with a mixture associated with both good and poor outcomes.

表1 MSI状态与结直肠癌患者的临床特征的关系[例(%)]
表2 MSI状态与结直肠癌患者的病理特征的关系[例(%)]
变量 MSS/MSI-L MSI-H 检验值 P
肿瘤部位 Z=-9.451 <0.001

右半结肠

266(22.8) 71(63.4)

左半结肠

367(31.4) 31(27.7)

直肠

535(45.8) 10(8.9)
肿瘤TNM分期 Z=-2.108 0.035

204(17.4) 11(9.80)

565(48.4) 84(75.00)

343(29.4) 16(14.30)

56(4.8) 1(0.90)
肿瘤T分期 Z=-2.397 0.017

1

62(5.3) 2(1.8)

2

185(15.8) 9(8.0)

3

814(69.7) 90(80.4)

4a

101(8.6) 10(8.9)

4b

6(0.5) 1(0.9)
肿瘤N分期 Z=-3.892 <0.001

0

781(66.9) 95(84.8)

1

255(21.8) 12(10.7)

2

132(11.3) 5(4.5)
肿瘤M分期 χ2=3.657 0.054

0

1 112(95.2) 111(99.1)

1

56(4.8) 1(0.9)
肿瘤分化 χ2=6.663 0.010

中高

816(69.9) 65(58.0)

352(30.1) 47(42.0)
印戒细胞 χ2=1.236 0.249

1 159(99.2) 110(98.2)

9(0.8) 2(1.8)
黏液成分 χ2=78.833 <0.001

996(85.3) 58(51.8)

172(14.7) 54(48.2)
病理形态 χ2=2.052 0.152

溃疡

797(68.2) 69(61.6)

隆起

371(31.8) 43(38.4)
最大直径(cm) χ2=39.656 <0.001

<4

503(43.1) 14(12.5)

≥4

665(56.9) 98(87.5)
癌结节 χ2=8.759 0.003

1 046(89.6) 110(98.2)

122(10.4) 2(1.8)
脉管侵犯 χ2=0.049 0.825

992(84.9) 96(85.7)

176(15.1) 16(14.3)
神经侵犯 χ2=10.238 0.001

985(84.3) 107(95.5)

183(15.7) 5(4.5)
LNR χ2=5.880 0.015

<0.25

1 073(91.9) 110(98.2)

≥0.25

95(8.1) 2(1.8)
淋巴结检出数(枚) 19(16,23) 22(18,30) Z=-5.019 <0.001
阳性淋巴结检出数(枚) 0(0,1) 0(0,0) Z=-3.667 <0.001
1
郑荣寿, 孙可欣, 张思维, 等. 2015年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2019, 41(1): 19-28.
2
Kawakami H, Zaanan A, Sinierope FA. Microsatellite instability testing and its role in the management of colorectal cancer[J]. Curr Treat Options Oncol, 2015, 16(7): 30.
3
Kazama Y, Watanabe T, Kanazawa T, et al. Microsatellite instability in poorly differentiated adenocarcinomas of the colon and rectum: relationship to clinicopathological features[J]. J Clin Pathol, 2007, 60(6): 701-704.
4
中国临床肿瘤学会结直肠癌专家委员会, 中国抗癌协会大肠癌专业委员会遗传学组, 中国医师协会结直肠肿瘤专业委员会遗传专委会. 结直肠癌及其他相关实体瘤微卫星不稳定性检测中国专家共识[J]. 中华肿瘤杂志. 2019, 41(10): 734-741.
5
Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer[J]. Cancer Res, 1998, 58(22): 5248-5257.
6
王畅. 微卫星状态对结肠癌术后辅助化疗决策的影响[J/CD]. 中华结直肠疾病电子杂志, 2018, 7(3): 207-213.
7
Al-Sohaily S, Biankin A, Leong R, et al. Molecular pathways in colorectal cancer[J]. J Gastroenterol Hepatol, 2012, 27(9): 1423-1431.
8
Shin US, Cho SS, Moon SM, et al. Is microsatellite instability really a good prognostic factor of colorectal cancer?[J]. Ann Coloproctol, 2014, 30(1): 28-34.
9
Karahan B, Argon A, Yıldırım M, et al. Relationship between MLH-1, MSH-2, PMS-2, MSH-6 expression and clinicopathological features in colorectal cancer[J]. Int J Clin Exp Pathol, 2015, 8(4): 4044-4053.
10
陈美丽, 李琳, 禹立霞, 等. 微卫星状态与术后大肠癌患者的临床及病理特征相关性研究[J]. 中国肿瘤临床, 2018, 45(3): 131-136.
11
Kim YH, Min BH, Choi HK, et al. Sporadic colorectal carcinomas with low-level microsatellite instability in Korea: do they form a distinct subgroup with distinguished clinicopathological features?[J]. J Surg Oncol, 2009, 99(6): 351-355.
12
Gupta R, Sinha S, Paul RN. The impact of microsatellite stability status in colorectal cancer[J]. Curr Probl Cancer, 2018, 42(6): 548-559.
13
Kang S, Na Y, Joung SY, et al. The significance of microsatellite instability in colorectal cancer after controlling for clinicopathological factors[J]. Medicine (Baltimore), 2018, 97(9): e0019.
14
Belt EJ, te Velde EA, Krijgsman O, et al. High lymph node yield is related to microsatellite instability in colon cancer[J]. Ann Surg Oncol, 2012, 19(4): 1222-1230.

URL    
15
Berg M, Guriby M, Nordgård O, et al. Influence of microsatellite instability and KRAS and BRAF mutations on lymph node harvest in stage I-III colon cancers[J]. Mol Med, 2013, 19(1): 286-293.
16
Phillips SM, Banerjea A, Feakins R, et al. Tumour-infiltrating lymphocytes in colorectal cancer with microsatellite instability are activated and cytotoxic[J]. Br J Surg, 2004, 91(4): 469-475.
17
Ogino S, Nosho K, Irahara N, et al. Lymphocytic reaction to colorectal cancer is associated with longer survival, independent of lymph node count, microsatellite instability, and CpG island methylator phenotype[J]. Clin Cancer Res, 2009, 15(20): 6412-6420.
18
MurphyJohn, PocardMarc, JassJeremy R, et al. Number and size of lymph nodes recovered from dukes B rectal cancers: correlation with prognosis and histologic antitumor immune response [J]. Dis Colon Rectum, 2007, 50(10): 1526-1534.

URL    
19
Wirta EV, Seppälä T, Friman M, et al. Immunoscore in mismatch repair-proficient and -deficient colon cancer[J]. J Pathol Clin Res, 2017, 3(3): 203-213.
20
MacQuarrie E, Arnason T, Gruchy J, et al. Microsatellite instability status does not predict total lymph node or negative lymph node retrieval in stage III colon cancer[J]. Hum Pathol, 2012, 43(8): 1258-1264.

URL    
[1] 罗青杉, 梅海涛, 郝家领, 蔡锦锋, 周润楷, 温玉刚. 连接蛋白43通过调控细胞周期抑制结直肠癌的增殖机制研究[J/OL]. 中华普通外科学文献(电子版), 2024, 18(05): 344-349.
[2] 徐逸男. 不同术式治疗梗阻性左半结直肠癌的疗效观察[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 72-75.
[3] 陈浩, 王萌. 胃印戒细胞癌的临床病理特征及治疗选择的研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 108-111.
[4] 孙建娜, 孔令军, 任崇禧, 穆坤, 王晓蕊. 266例首诊Ⅳ期乳腺癌手术患者预后分析[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(05): 502-505.
[5] 严虹霞, 王晓娟, 张毅勋. 2 型糖尿病对结直肠癌患者肿瘤标记物、临床病理及预后的影响[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 483-487.
[6] 赵磊, 刘文志, 林峰, 于剑, 孙铭骏, 崔佑刚, 张旭, 衣宇鹏, 于宝胜, 冯宁. 深部热疗在改善结直肠癌术后辅助化疗副反应及生活质量中的作用研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 488-493.
[7] 黄海洋, 邝永龙, 陈嘉胜. 基层医院结直肠肿瘤经自然腔道取标本手术30 例分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 510-518.
[8] 韩加刚, 王振军. 梗阻性左半结肠癌的治疗策略[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 450-458.
[9] 梁轩豪, 李小荣, 李亮, 林昌伟. 肠梗阻支架置入术联合新辅助化疗治疗结直肠癌急性肠梗阻的疗效及其预后的Meta 分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 472-482.
[10] 任佳琪, 刁德昌, 何自衍, 张雪阳, 唐新, 李文娟, 李洪明, 卢新泉, 易小江. 网膜融合线导向的脾曲游离技术在左半结肠癌根治术中的应用[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 362-367.
[11] 张迪, 王春霞, 张学东, 李发馨, 庞淅文, 陈一锋, 张维胜, 王涛. 梗阻性左半结直肠癌自膨式金属支架置入后行腹腔镜手术与开腹手术的短期临床疗效比较[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 375-380.
[12] 张蔚林, 王哲学, 白峻阁, 黄忠诚, 肖志刚. 利用TCGA数据库构建基于miRNA的结直肠癌列线图预后模型[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 381-388.
[13] 张伟伟, 陈启, 翁和语, 黄亮. 随机森林模型预测T1 期结直肠癌淋巴结转移的初步研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 389-393.
[14] 丁富贵, 吴泽涛, 董卫国. 家族性腺瘤性息肉病临床特征及生物信息学分析[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 512-518.
[15] 甘曦, 廖鑫. 胃癌旁肿瘤沉积与CT影像学特征、血清指标及病理特征的关联性分析[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(05): 422-425.
阅读次数
全文


摘要