Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

KRAS and BRAF gene mutations and DNA mismatch repair status in Chinese colorectal carcinoma patients

AIM:To investigate gene mutations and DNA mismatch repair(MMR) protein abnormality in Chinese colorectalcarcinoma(CRC) patients and their correlations with clinicopathologic features.METHODS:Clinical and pathological information for 535 patients including 538 tumors was reviewed and recorded.Mutation analyses for exon 2 of KRAS gene and exon 15 of BRAF gene were performed by Sanger sequencing except that in 9 tumors amplification refractory mutation system PCR was used.Expression of MMR proteins including MHL1,MSH2,MSH6 and PMS2 was evaluated by immunohistochemistry.Correlations of KRAS and BRAF mutation status and the expression status of MMR proteins with age,gender,cancer stage,location,and histology were analyzed.Correlations between KRAS or BRAF mutations and MMR protein expression were also explored.RESULTS:The overall frequencies of KRAS and BRAF mutations were 37.9% and 4.4%,respectively.KRAS mutations were more common in patients ≥ 50 years old(39.8% vs 22% in patients < 50 years old,P < 0.05).The frequencies of BRAF mutants were higher in tumors from females(6.6% vs males 2.8%,P < 0.05),located in the right colon(9.6% vs 2.1% in the left colon,1.8% in the rectum,P < 0.01),with mucinous differentiation(9.8% vs 2.8% without mucinous differentiation,P < 0.01),or being poorly differentiated(9.5% vs 3.4% well/moderately differentiated,P < 0.05).MMR deficiency was strongly associated with proximal location(20.5% in the right colon vs 9.2% in the left colon and 5.1% in the rectum,P < 0.001),early cancer stage(15.0% in stages Ⅰ-Ⅱ vs 7.7% in stages Ⅲ-Ⅳ,P < 0.05),and mucinous differentiation(20.2% vs 9.2% without mucin,P < 0.01).A higher frequency of MLH1/PMS2 loss was found in females(9.2% vs 4.4% in males,P < 0.05),and MSH2/MSH6 loss tended to be seen in younger(<50 years old) patients(12.0% vs 4.0% ≥ 50 years old,P < 0.05).MMR deficient tumors were less likely to have KRAS mutations(18.8% vs 41.7% in MMR proficient tumors,P < 0.05) and tumorswith abnormal MLH1/PMS2 tended to harbor BRAF mutations(15.4% vs 4.2% in MMR proficient tumors,P < 0.05).CONCLUSION:The frequency of sporadic CRCs having BRAF mutation,MLH1 deficiency and MSI in Chinese population may be lower than that in the Western population.

Preliminary Studies on Base Substitutions and Repair of DNA Mismatch Damage Stimulated by Low Energy N^+ Ion Beam Implantation in Escherichia coli

Ever since the low energy N+ ion beam has been accepted that the mutation effects of ionizing radiation are attributed mainly to direct or indirect damage to DNA. Evidences based on naked DNA irradiation in support of a mutation spectrum appears to be consistent, but direct proof of such results in vivo are limited. Using mutS, dam and/or dcm defective Eschericha coli imitator strains, an preliminary experimental system on induction of in vivo mutation spectra of low energy N+ ion beam has been established in this study. It was observed that the mutation rates of rifampicin resistance induced by N+ implantation were quite high, ranging from 9.2 x 10~8 to 4.9× 10~5 at the dosage of 5.2×1014 ions/cm2. Strains all had more than 90-fold higher mutation rate than its spontaneous mutation rate determined by this method. It reveals that base substitutions involve in induction of mutation of low energy nitrogen ion beam implantation. The mutation rates of mutator strains were nearly 500-fold (GM2929), 400-fold (GM5864) and 6-fold larger than that of AB1157. The GM2929 and GM5864 both lose the ability of repair DNA mismatch damage by virtue of both dam and dcm pathways defective (GM2929) or failing to assemble the repair complex (GM5864) respectively. It may explain the both strains had a similar higher mutation rate than GM124 did. It indicated that DNA cytosine methylase might play an important role in mismatch repair of DNA damage induced by N+ implantation. The further related research were also discussed.

Helicobacter pylori infection and expression of DNA mismatch repair proteins

AIM： TO determine the expression of DNA （MMR） proteins, including hMLH1 and hMSH2, in gastric epithelial cells in the patients with or without Helicobacter pylori （H pylori）-infected gastritis. METHODS： Fifty Hpylori-positive patients and 50 H pylori-negative patients were enrolled in the study. During endoscopy of patients with non-ulcer dyspepsia, two antral and two corpus biopsies were taken for histological examination （Giemsa stain） and for immunohistochemical staining of hMLH1 and hMSH2. RESULTS： The percentage of epithelial cell nuclei that demonstrated positivity for hMLH1 staining was 84.14 ± 7.32% in Hpylori-negative patients, while it was 73.34 ±10.10% in Hpylori-positive patients （P 〈 0.0001）. No significant difference was seen between the two groups regarding the percentage of epithelial cell nuclei that demonstrated positivity for hMSH2 staining （81.16±8.32% in H pylori-negative versus 78.24 ± 8.71% in Hpylori-positive patients; P = 0.09）. CONCLUSION： This study indicates that Hpylori might promote development of gastric carcinoma at least in part through its ability to affect the DNA MMR system

Association between DNA mismatch repair gene polymorphisms and platinum-based chemotherapy toxicity in non-small cell lung cancer patients

Background:Chemotherapy toxicity is a serious problem from which non-small cell lung cancer(NSCLC) patients suffer.The mismatch repair(MMR) system is associated with platinum-based chemotherapy toxicity in NSCLC patients.In this study,we aimed to investigate the relationship between genetic polymorphisms in the MMR pathway and platinum-based chemotherapy toxicity in NSCLC patients.Methods:A total of 220 Chinese lung cancer patients who received at least two cycles of platinum-based chemotherapy were recruited for this study.Toxicity was evaluated in each patient after two cycles of chemotherapy.A total of 44 single nucleotide polymorphisms were selected to investigate their associations with platinum-based chemotherapy toxicity.Results:MutS homolog 2[MSH2) rs6544991[odds ratio(OR) 2.98,95%confidence interval(CI) 1.20-7.40,P = 0.019]was associated with gastrointestinal toxicity in the dominant model;MSH3 rs6151627(OR 2.38,95%CI 1.23-4.60,P = 0.010),rs6151670(OR 2.05,95%CI 1.07-3.93,P = 0.031),and rs7709909(OR 2.38,95%CI 1.23-4.64,P = 0.010)were associated with hematologic toxicity in the dominant model.Additionally,MSH5 rs805304 was significantly associated with overall toxicity(OR 2.21,95%CI 1.19-4.09,P = 0.012),and M5H5 rs707939 was significantly associated with both overall toxicity(OR 0.42,95%CI 0.23-0.76,P = 0.004) and gastrointestinal toxicity(OR 0.44,95%CI 0.20-0.96,P = 0.038) in the dominant model.Conclusion:Genetic polymorphisms in the MMR pathway are potential clinical markers for predicting chemotherapy toxicity in NSCLC patients.

The Role of DNA Mismatch Repair and Recombination in the Processing of DNA Alkylating Damage in Living Yeast Cells

It is proposed that mismatch repair (MMR) mediates the cytotoxic effects of DNA damaging agents by exerting a futile repair pathway which leads to double strand breaks (DSBs). Previous reports indicate that the sensitivity of cells defective in homologous recombination (HR) to DNA alkylation is reduced by defects in MMR genes. We have assessed the contribution of different MMR genes to the processing of alkylation damage in vivo. We have directly visualized recombination complexes formed upon DNA damage using fluorescent protein (FP) fusions. We find that msh6 mutants are more resistant than wild type cells to MNNG, and that an msh6 mutation rescues the sensitivity of rad52 strains more efficiently than an msh3 mutation. Analysis of RAD52-GFP tagged strains indicate that MNNG increases repair foci formation, and that the inactivation of the MHS2 and MSH6 genes but not the MSH3 gene result in a reduction of the number of foci formed. In addition, in the absence of HR, NHEJ could process the MNNG-induced DSBs as indicated by the formation of NHEJ-GFP tagged foci. These data suggest that processing of the alkylation damage by MMR, mainly by MSH2-MSH6, is required for recruitment of recombination proteins to the damage site for repair.

Evaluation of 30 DNA damage response and 6 mismatch repair gene mutations as biomarkers for immunotherapy outcomes across multiple solid tumor types

Objective:DNA damage response(DDR)genes have low mutation rates,which may restrict their clinical applications in predicting the outcomes of immune checkpoint inhibitor(ICI)treatment.Thus,a systemic analysis of multiple DDR genes is needed to identify potential biomarkers of ICI efficacy.Methods:A total of 39,631 patients with mutation data were selected from the cBioPortal database.A total of 155 patients with mutation data were obtained from the Fudan University Shanghai Cancer Center(FUSCC).A total of 1,660 patients from the MSK-IMPACT cohort who underwent ICI treatment were selected for survival analysis.A total of 249 patients who underwent ICI treatment from the Dana-Farber Cancer Institute(DFCI)cohort were obtained from a published dataset.The Cancer Genome Atlas(TCGA)level 3 RNA-Seq version 2 RSEM data for gastric cancer were downloaded from cBioPortal.Results:Six MMR and 30 DDR genes were included in this study.Six MMR and 20 DDR gene mutations were found to predict the therapeutic efficacy of ICI,and most of them predicted the therapeutic efficacy of ICI,in a manner dependent on TMB,except for 4 combined DDR gene mutations,which were associated with the therapeutic efficacy of ICI independently of the TMB.Single MMR/DDR genes showed low mutation rates;however,the mutation rate of all the MMR/DDR genes associated with the therapeutic efficacy of ICI was relatively high,reaching 10%–30%in several cancer types.Conclusions:Coanalysis of multiple MMR/DDR mutations aids in selecting patients who are potential candidates for immunotherapy.

Microsatellite instability and expression of DNA mismatch repair genes in malignant astrocytic tumors from adult and pediatric patients

Microsatellite instability (MSI) is used as a molecular marker for defective DNA mismatch repair (MMR) genes.We report here alterations of MSI in 15 malignant astrocytomas (WHO grade Ⅲ) and glioblastomas (GBM; WHO grade Ⅳ) of pediatric patients (2-21 years) and 12 GBM from adults (44-68 years) by comparative analysis of BAT25/BAT26 loci and 10 other microsatellite markers. High-level microsatellite instability (MSI-H) occurred in 4 of the 15 pediatric cases (26.7%) and in 1 of the 12 adult GBM cases (8.3%). Low-level mi-

Constitutional Mismatch Repair-Deficiency Syndrome Is a Rare Cause of Cancer Even in a Highly Consanguineous Population

Biallelic germline mutations in the mismatch repair genes, including MLH1, MSH2, MSH6 or PMS2, lead to a recessive constitutional mismatch repair-deficiency (CMMR-D) syndrome characterized by early onset malignancies in children and young adults. Because consanguinity unmasks autosomal recessive disorders, we hypothesized that the frequency of CMMR-D is inflated in the highly consanguineous population of Saudi Arabia. In this study, 371 pediatric and young adult?patient samples from Saudi Arabia that cover the tumor spectrum of CMMR-D syndrome were analyzed for biallelic germline mutations in the MLH1, MSH2, MSH6 and PMS2 with the use of direct genomic sequencing. However, none of the 371 patients involved in the study was found to have biallelic pathological mutations of MLH1, MSH2, MSH6 or PMS2. This result indicates that CMMR-D is exceptionally rare among pediatric cancer patients and adult early onset cancer patients, even in the highly consanguineous Saudi population. Our findings suggest that larger cohorts will be needed, particularly in outbred populations, to determine the frequency of CMMR-D and that routine screening for this syndrome among cancer patients is not warranted.

基于纳米金胶标记DNA探针的电化学DNA传感器研究

以纳米金胶为标记物 ,将其标记于人工合成的 5 -端巯基修饰的寡聚核苷酸片段上 ,制成了具有电化学活性的金胶标记 DNA电化学探针 ;在一定条件下 ,使其与固定在玻碳电极表面的靶序列进行杂交反应 ,利用 ss DNA与其互补链杂交的高度序列选择性和极强的分子识别能力 ,以及纳米金胶的电化学活性 ,实现对特定序列 DNA片段的电化学检测以及对 DNA碱基突变的识别 .

寡聚酰胺为探针的电化学DNA生物传感器

DNA分子中的碱基对可以长程传递电荷,DNA分子中的碱基π堆积结构为电荷的长程传递提供了良好的通道.电荷在DNA分子中的传递受碱基序列的影响,利用这种性质可以构建DNA碱基错配检测的电化学传感器.寡聚酰胺能和DNA以小沟绑定方式高亲和力地结合,并且具有序列识别功能,本文以带有硝基官能团的寡聚酰胺分子为电化学探针,设计了电化学DNA生物传感器.结果显示,寡聚酰胺与DNA修饰电极作用后,电化学响应显著增强,并且可以作为检测DNA碱基错配的电化学探针分子.

大鳞副泥鳅群体线粒体DNA D-loop序列遗传变异分析

为探明大鳞副泥鳅野生资源状况,利用线粒体DNA D-loop序列,对天津5个大鳞副泥鳅自然群体的遗传多样性、遗传结构及种群历史动态进行分析。5个群体72个个体的D-loop基因序列全长912~914bp,其中多态性位点30个,共检测到22个单倍型,平均单倍型多样性和核苷酸多样性分别为0.813和0.0015,呈现高单倍型多样性和低核苷酸多样性的模式。5个群体间的遗传分化指数为-0.0205~0.0795,总的遗传分化指数为0.0712,属中等程度的遗传分化。单倍型网络进化图和单倍型系统发育树均未显示出明显的地理分布格局,中性检验和核苷酸不配对分布分析均表明,大鳞副泥鳅经历过种群扩张,扩张事件发生在第四纪更新世晚期。研究结果表明,应加强5个湿地大鳞副泥鳅群体的保护,适时开展大鳞副泥鳅良种选育工作,减少对大鳞副泥鳅野生资源的破坏。

DNA错配修复与癌症的发生及治疗

DNA错配修复是细胞复制后的一种修复机制,具有维持DNA复制保真度,控制基因变异的作用。DNA错配修复缺陷使整个基因组不稳定,最终会导致肿瘤和癌症的发生。DNA错配修复系统不仅通过矫正在DNA重组和复制过程中产生的碱基错配而保持基因组的稳定,而且通过诱导DNA损伤细胞的凋亡而消除由突变细胞生长形成的癌变。错配修复缺陷细胞的抗药性也引起了癌症化疗研究方面的关注。大多数情况下,错配修复健全型细胞对肿瘤化疗药物敏感,而错配修复缺陷细胞却有较高的抗性。DNA错配修复系统通过修复和诱导细胞凋亡维护基因组稳定的功能,显示了错配修复途径在癌症生物学和分子医学中的重要性。

DNA错配修复蛋白表达与胃腺癌临床病理特征的关系及意义

目的:检测DNA错配修复(mismatch repair,MMR)主要蛋白(MLH1、MSH2、MSH6和PMS2)在人胃腺癌组织中的表达,并分析错配修复缺陷(defective mismatch repair,dMMR)与胃腺癌临床病理因素及预后的关系。方法:采用免疫组织化学染色法检测4种MMR蛋白(MLH1、MSH2、MSH6和PMS2)在120例人胃腺癌组织中的表达,并从癌症基因组图谱(The Cancer Genome Atlas,TCGA)公共数据库下载432例胃腺癌患者的临床病理资料和微卫星不稳定性(microsatellite instability,MSI)的检测结果,分析MSI与胃腺癌临床病理特征的关系,利用TCGA的数据分析高频度微卫星不稳定(MSI-H)与胃腺癌患者预后的关系。结果:免疫组化染色结果显示在120例胃腺癌组织中,MMR蛋白表达正常(pMMR)组106例(88.3%),MMR蛋白表达缺失(dMMR)组14例(11.7%),其中MLH1缺失2例(1.7%)、PMS2缺失13例(10.8%)、MLH1和PMS2共同缺失2例(1.7%)、MSH2和MSH6共同缺失1例(0.8%)。统计分析结果显示,dMMR与胃腺癌淋巴结转移相关( P =0.022),而与其他临床病理因素无关。TCGA数据统计分析结果显示,MSI-H与胃腺癌患者年龄( P =0.001)、性别( P =0.000)、原发肿瘤部位( P =0.000)、Lauren分型( P =0.011)、肿瘤浸润深度T分期( P =0.024)、淋巴结有无转移( P =0.008)有关。Kaplan-Meier生存分析结果显示MSI-H型胃腺癌患者有预后更好的趋势,但差异不具有统计学意义( P =0.070)。结论:120例中国胃腺癌患者中MSI/dMMR型胃腺癌占比为11.7%,且dMMR状态与胃腺癌的淋巴结转移呈负相关;MSI-H型胃腺癌患者具有年龄大、多为女性、肿瘤多位于胃远端、肿瘤浸润深度T分期低、无淋巴结转移的特征,且MSI-H型胃腺癌具有预后更好的趋势,但不具有统计学意义。MSI状态与胃癌预后的关系尚需进一步深入研究和大样本数据的验证。

DNA错配修复基因甲基化在H446细胞获得性耐药中的作用

目的探讨DNA错配修复基因MLH1(human MutL homolog1)、MSH2(human MutS homolog2)甲基化在人小细胞肺癌H446细胞获得性耐药中的作用。方法RT-PCR及Western blot法检测H446细胞及其多药耐药细胞H446/DDP中MLH1、MSH2基因的mRNA表达和蛋白表达,甲基化特异性PCR(MSP)法检测MLH1、MSH2基因启动子CpG岛甲基化状态。结果H446/DDP细胞中MLH1、MSH2基因的mRNA及蛋白水平均较H446细胞显著降低(P<0.01),且其启动子甲基化程度明显增强。结论DNA错配修复基因MLH1、MSH2启动子甲基化诱导其表达下调可能是人小细胞肺癌获得性耐药的重要机制之一。

结直肠癌DNA错配修复蛋白的表达及临床病理学意义

目的探讨错配修复蛋白在结直肠癌中的表达及临床病理学意义。方法采用免疫组织化学法,对55例结直肠癌组织标本进行MLH1、MSH2、MSH6、PMS2四种错配修复蛋白检测,同时观察其与临床病理学参数关系。采用real-time PCR法对其中10例进行鼠类肉瘤病毒癌基因(KRAS)第2号外显子和鼠类肉瘤滤过性毒菌致癌基因同源体B1(BRAF)基因第15号外显子突变检测。结果 55例患者中50例四种蛋白均阳性表达,为微卫星稳定(MSS),5例患者蛋白表达有缺失,提示为高频微卫星不稳定(MSI-H),缺失率为9.09%,其中4例MLH1、PMS2联合缺失,1例MSH2、MSH6联合缺失;MSI-H患者肿瘤多发生在右半结肠,与MSS患者相比差异显著(P=0.01),其中3例为黏液癌或伴黏液分化癌,均无淋巴结转移;10例行KRAS及BRAF突变检测的病例中,6例存在KRAS基因突变,1例存在BRAF基因突变且表现为MLH1、PMS2表达联合缺失。结论 MSI-H结直肠癌患者多发生在右半结肠,这类患者有以黏液癌或伴有黏液分化癌多见及淋巴结转移少见为特征的趋势;MSI-H与MSS患者相比,在年龄、性别、肿块大小、肿瘤分级及分期方面无显著差异;发现散发性结直肠癌中具有微卫星不稳定的病例,结合其他检测可进一步指导临床用药,为新的治疗方案提供理论依据。

DNA错配修复系统组成和功能的研究进展

DNA错配修复(Mismateh repair,MMR)系统广泛的存在于从原核到真核的生物体中,是进化上保守的生化通路。MMR系统由一系列特异性修复DNA碱基错配的酶分子(错配修复基因产物)组成。细胞由于此系统的存在使DNA复制保持忠实性,从而保持遗传物质的完整性和稳定性,避免遗传物质发生突变。MMR系统基因的失活会导致自发突变率的明显增加,从而导致微卫星不稳定(MSI),可能引发某些肿瘤发生。近年来,MMR系统的研究越来越受到学者的重视,对MMR作用机制及组成该系统的几种酶蛋白结构与功能方面的研究不断深入,加深了对MMR系统的理解。这些为MMR系统相关的应用研究,尤其是为肿瘤发生奠定了理论的基础。本文重点讨论了错配修复系统的蛋白组成、各蛋白的功能及它们如何相互协调发挥作用的最新研究进展。

DNA损伤修复机制——解读2015年诺贝尔化学奖

Tomas Lindahl,Paul Modrich和Aziz Sancar三位科学家因发现"DNA损伤修复机制"获得了2015年诺贝尔化学奖.Lindahl首次发现Escherichia Coli中参与碱基切除修复的第一个蛋白质——尿嘧啶-DNA糖基化酶(UNG);Modrich重建了错配修复的体外系统,从大肠杆菌到哺乳动物深入探究了错配修复的机制;Sancar利用纯化的Uvr A、Uvr B、Uvr C重建了核苷酸切除修复的关键步骤,阐述了核苷酸切除修复的分子机制.DNA损伤是由生物所处体外环境和体内因素共同导致的,面对不同种类的损伤,机体启动多种不同的修复机制修复损伤,保护基因组稳定性.这些修复机制包括:光修复(light repairing);核苷酸切除修复(nucleotide excision repair,NER);碱基切除修复(base excision repair,BER);错配修复(mismatch repair,MMR);以及DNA双链断裂修复(DNA double strand breaks repair,DSBR).其中DNA双链断裂修复又分同源重组(homologous recombination,HR)和非同源末端连接(non-homologous end joining,NHEJ)两种方式.本文将对上述几种修复的机制进行总结与讨论.

DNA错配修复基因hMLH1与肿瘤及化疗耐药相关性的研究进展

DNA是生命活动最重要的遗传物质。DNA复制产生的误差(碱基错配)是一种重要的损伤。若DNA损伤得不到修复,将会导致基因的突变,其中一部分突变有利于物种的进化,而另一部分将导致细胞恶化和死亡。DNA错配修复系统(mismatch repair system,MMR)是人体细胞中存在的一种能识别并修复DNA碱基错配的安全保障系统。到目前为止,已从人体细胞中共分离克隆到9种MMR基因。hMLH1基因是一系列DNA错配修复基因中最重要的一种,也是MMR系统的重要成分,其甲基化可导致MMR缺陷。近年来的研究发现,hMLH1的失活与肿瘤发生发展有关,并可能因此导致肿瘤对某些抗肿瘤药物耐药。

DNA错配修复蛋白缺失与Ⅱ、Ⅲ期结肠癌根治术后复发转移及预后的关系

目的探讨DNA错配修复蛋白(MMR)缺失与Ⅱ、Ⅲ期结肠癌根治术后复发转移及预后的关系。方法采用免疫组织化学法检测294例结肠癌患者手术标本的MMR表达,回顾性分析其表达对结肠癌患者临床病理参数及生存率的影响。结果多因素分析结果显示,肿瘤部位、分化程度和分期是影响MMR表达状态的独立性危险因素(P<0.05);单因素结果显示,年龄、分化程度、T和N分期是影响患者复发转移率、总体生存率的危险因素;仅有N分期是影响患者复发转移率的独立性危险因素;仅有肿瘤分化程度、N分期和MMR缺失是影响患者总体生存率的独立性危险因素。220例DNA错配修复缺陷蛋白完整(pMMR)患者中,69例出现复发转移(31.4%),48例死亡(21.8%);74例DNA错配修复蛋白缺失(dMMR)患者中,13例出现复发转移(17.6%),9例死亡(12.2%)。两组患者的无病生存率(P=0.034)、总体生存率(P=0.047)差异均具有统计学意义。结论肿瘤部位、分化程度和分期与MMR表达状态密切相关;MMR表达缺失患者预后明显较差,可作为判断患者预后的一个潜在标志物。