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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
作者姓名:张冬生  封益飞  王勇  胥子玮  唐俊伟  黄远健  张川  孙跃明
作者单位:南京医科大学第一附属医院结直肠外科
基金项目:国家重点研发计划[No.2017YFC0908200(AH17)]。
摘    要: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1280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M(P25,P75)表示,组间比较采用曼-惠特尼U检验。结果在1280例患者中,112例(8.7%)为MSI-H,79例(6.2%)为MSI-L,1089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。

关 键 词:结直肠肿瘤  病理特征  微卫星状态

Study on the relationship between microsatellite instability status and clinicopathological characteristics of colorectal cancer patients
Authors:Zhang Dongsheng  Feng Yifei  Wang Yong  Xu Ziwei  Tang Junwei  Huang Yuanjian  Zhang Chuan  Sun Yueming
Institution:(The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China)
Abstract:Objective To identify the relationship between microsatellite instability(MSI)status and clinicopathological characteristics of colorectal cancer patients.Methods The clinicopathological data of 1280 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 1280 colorectal cancer patients,112(8.7%)patients were MSI-H,79(6.2%)were MSI-L,and 1089(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/m L,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.
Keywords:Colorectal neoplasms  Clinicopathological characteristics  Microsatellite status
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