错配修复蛋白表达及RAS基因突变与结直肠癌临床病理特征的关系

目的探讨结直肠癌组织中错配修复(mismatch repair,MMR)蛋白表达及RAS基因突变状态与临床病理特征的相关性。方法采用免疫组化法检测186例结直肠癌组织中4种MMR蛋白(MSH2、MSH6、MLH1、PMS2)的表达,并采用ARMS-PCR法检测RAS基因突变状态。结果186例结直肠癌组织中MMR蛋白表达缺失率为6.99%(13/186),其中MSH2和MSH6共同缺失2例,MLH1和PMS2共同缺失9例,MSH6单独缺失1例,PMS2单独缺失1例。RAS突变者97例(52.15%),其中KRAS突变88例(47.31%),NRAS突变9例(4.84%)。MMR蛋白表达缺失多发生于50岁以下、肿瘤部位多为右半结肠、黏液腺癌、肿瘤低分化、肿瘤分期Ⅰ+Ⅱ期的患者(P<0.05)。RAS突变状态与结直肠癌临床病理特征无相关性(P>0.05)。MMR蛋白表达缺失病例中,RAS突变状态与肿瘤是否伴黏液腺癌成分有显著相关性(P=0.015),伴RAS突变病例不伴有黏液腺癌,而RAS野生型多伴黏液腺癌。结论MMR蛋白表达状态与结直肠癌患者年龄、肿瘤部位、分化程度、肿瘤分期和病理分型有关,结合RAS突变检测,可为结直肠癌患者的个体化治疗提供更多的依据。     

子宫内膜癌组织中COX-2、YKL-40、NF-κB的表达及临床意义

目的探究子宫内膜癌组织中环氧合酶-2(COX-2)、甲壳质酶蛋白40(YKL-40)、核转录因子κB(NF-κB)的表达及临床意义。方法选择2014年2月至2018年12月我院妇科收集的80例子宫内膜癌组织及同期行子宫切除的40例正常子宫内膜组织标本作为研究样本,采用免疫组化方法测定组织中COX-2、YKL-40、NF-κB蛋白表达情况,分析子宫内膜癌组织蛋白表达与患者临床参数、预后的相关性。结果子宫内膜癌组织COX-2、YKL-40、NF-κB蛋白阳性表达率显著高于正常内膜组织(P<0.05);子宫内膜癌患者COX-2水平与患者FIGO分期、淋巴结转移相关(P<0.05);YKL-40、NF-κB水平与FIGO分期、分化程度、肌层浸润、淋巴结转移相关(P<0.05);Kaplan-Meier生存曲线显示,COX-2、YKL-40、NF-κB阳性表达患者总体生存率均显著低于阴性表达患者;COX多因素分析示,在矫正其他临床资料后,YKL-40、NF-κB蛋白阳性表达是子宫内膜癌患者预后不良的独立危险因素(P<0.05)。结论子宫内膜癌组织存在COX-2、YKL-40、NF-κB等阳性表达率的升高,与肿瘤侵袭性及预后相关,可作为病情判断及预后预测的参考指标。     

转移抑制基因KAI1表达与子宫内膜腺癌进展的关系

目的探讨KAI1蛋白表达与子宫内膜腺癌进展的关系。方法应用免疫组化SP法检测20例正常子宫内膜组织、17例子宫内膜不典型增生和48例子宫内膜腺癌组织中KAI1蛋白的表达情况。结果子宫内膜腺癌中KAI1蛋白的阳性率明显低于正常内膜组织(P<0.01)和内膜不典型增生组织(P<0.01)。KAI1蛋白的表达随子宫内膜腺癌恶性程度(P<0.01),肌层浸润深度(P<0.01)及手术-病理分期(P<0.05)的增高而降低,并与子宫内膜腺癌组织学类型有关(P<0.01),有淋巴结转移的组织中KAI1蛋白阳性率明显低于无转移组织(P<0.01)。KAI1阴性的患者总的生存率低于阳性者(P<0.01,<0.01)。结论KAI1蛋白在子宫内膜腺癌的恶性进展中表达下调,有望成为内膜癌恶性程度评估,转移预测和判断预后的有效指标。     

结直肠癌错配修复蛋白与临床病理特征的关系

目的:分析结直肠癌(Colorectal cancer,CRC)患者错配修复(Mismatch Repair,MMR)蛋白与临床病理特征的关系.方法:选取2018年10月～2021年10月于本院接受根治术治疗的116例CRC患者作为研究对象.于根治术中采集患者病理标本,检测MMR蛋白表达情况和CRC组织的临床病理特征,分析MMR蛋白表达与临床病理特征的关系.结果:所有患者中,MMR蛋白表达阳性者94例,MMR蛋白表达缺失者22例;其中MutL同源物1(MutL homolog 1,MLH1)、减数分裂后分离蛋白2(Post-meiotic segregation 2,PMS2)、MutL同源物2(MutS protein homolog 2,MSH2)、MutL同源物6(MutS homolog 6,MSH6)蛋白表达缺失者分别为9例、11例、6例、6例,MLH1和PMS2蛋白共同缺失者4例,MSH2和MSH6蛋白共同缺失者6例,未见4种蛋白共同缺失患者.不同肿瘤TNM分期、肿瘤部位、肿瘤直径、分化程度患者的MMR蛋白表达缺失具有明显差异(P<0.05);MMR蛋白表达与肿瘤部位、肿瘤TNM分期、分化程度、肿瘤直径呈正相关(P<0.05).结论:CRC患者MMR蛋白缺失与肿瘤部位、肿瘤TNM分期、分化程度、肿瘤直径呈正相关.     

BRCA1在子宫内膜癌中的变化与预后的相关性分析

目的:分析乳腺癌易感基因1(Breast cancer susceptibility gene 1,BRCA1)在子宫内膜癌中的变化与预后的相关性.方法:收集本院2017年12月至2020年6月收治的91例子宫内膜癌患者的临床资料作为研究对象的研究组(癌组织),另选择距癌旁3cm处的正常组织作为对照组.比较两组患者子宫内膜组织BRCAl阳性表达率;对患者进行1年随访,分析影响其预后生存的危险因素.结果:研究组BRCAl阳性表达率为31.87％,明显低于对照组的95.60％(P<0.05).临床分期(Ⅲ～Ⅳ期)、淋巴结转移(有)、组织分化(G3)、肌层浸润(≥1/2)及BRCAl(阴性)为影响子宫内膜癌患者预后生存的独立危险因素(P<0.05).结论:BRCAl过度表达可能与子宫内膜癌发生、发展有关,可作为判断子宫内膜癌病情、预后的辅助指标.     

子宫内膜癌组织中cyclin E和p27表达的相关性及其与临床预后的关系

目的 :探讨子宫内膜癌组织中cyclinE与 p2 7表达的相关性及其与临床预后的关系。方法 :用免疫组化方法检测 40例子宫内膜癌、10例子宫内膜不典型增生、2 0例正常子宫内膜组织中cyclinE和p2 7的表达 ,并用Log Rank检验p2 7蛋白和cyclinE蛋白表达与子宫内膜癌患者生存率的关系。结果 :cyclinE表达的阳性率 ,子宫内膜癌组显著高于内膜不典型增生组和正常子宫内膜组 (P <0 .0 5 )。p2 7表达与子宫内膜癌的组织学分级、手术分期及肌层浸润深度有关 (P <0 .0 5 )。cyclinE与p2 7的表达呈负相关。cyclinE蛋白表达阳性患者生存率低于阴性患者 ,p2 7蛋白表达阳性患者生存率高于阴性患者 ,但无统计学意义 (P >0 .0 5 )。结论 :cyclinE对子宫内膜癌的发生可能起一定作用 ,p2 7则与抑制子宫内膜癌的进展有关 ,并可能成为判断预后的有用指标     

Fhit、p53表达与子宫内膜癌发生和发展的相关性

目的　探讨正常子宫内膜、子宫内膜增殖症及内膜癌组织中Fhit、p53蛋白表达,以及与子宫内膜癌发生、发展的关 系。方法　应用免疫组化S P法检测37例正常子宫内膜组织、27例单纯型增生过长、28例复杂型增生过长、38例子宫内膜癌 组织中Fhit、p53蛋白的表达。结果　在正常子宫内膜(增生期、分泌期)、子宫内膜增殖症(单纯型增生过长、复杂型增生过 长、不典型增生)、子宫内膜腺癌组织中Fhit蛋白的阳性表达率依次递增,差异有显著性(χ2=33.726,P<0.005)。p53蛋白的 阳性表达率也依次递增,差异有显著性(χ2=58.474,P<0.005)。在腺瘤型增生过长、不典型增生及子宫内膜腺癌组织中Fhit (χ2=6.571,P=0.037)、p53(χ2=6.915,P=0.032)蛋白的阳性表达率依次递增,差异有显著性。Fisher精确概率检验显示不 同肌层浸润组Fhit(P=0.033)、p53(P=0.034)蛋白的表达差异有统计学意义,而在年龄、是否绝经、手术病理分期、组织学分 级组的表达无统计学意义(P>0.05)。Spearman等级相关分析显示Fhit、p53蛋白表达呈正相关(r=0.900,P<0.05)。在月 经期内膜的腺上皮细胞胞质中的Fhit蛋白阳性表达率为72.72%。结论　Fhit、p53蛋白的表达与子宫内膜癌的发生相关。 Fhit基因可能成为子宫内膜组织早期癌变的分子标记物。     

MLH1、MSH2、MSH6和PMS2蛋白在结直肠癌中的表达及在Lynch综合征筛查中的意义

目的探讨错配修复(mismatch repair,MMR)蛋白MLH1、MSH2、MSH6和PMS2在结直肠癌中的表达及其临床意义。方法采用免疫组化En Vision两步法检测102例结直肠癌组织中MLH1、MSH2、MSH6和PMS2蛋白表达缺失情况,分析蛋白表达缺失与结直肠癌临床病理特征的关系,并对其中20例进行微卫星不稳定(microsatellite instability,MSI)检测。结果 102例结直肠癌有15例(14.7%)发生MMR蛋白表达缺失,MLH1、MSH2、MSH6、PMS2蛋白表达缺失率分别为12.7%(13/102)、3.9%(4/102)、4.9%(5/102)、10.8%(11/102)。结直肠癌标本中MLH1、MSH2、MSH6、PMS2的蛋白表达缺失与患者性别、年龄、肿瘤大小、浸润深度、淋巴结转移无关(P0.05);MLH1与PMS2蛋白表达缺失与组织学分化高低相关(P0.05)。进行MSI检测的10例MMR蛋白缺失病例中有2例(2.0%)为高频微卫星不稳定(microsatellite instability-high,MSI-H),其余8例为微卫星稳定(microsatellite stability,MSS);另10例无MMR蛋白缺失的病例微卫星状态均为低频微卫星不稳定(microsatellite instability-low,MSI-L)/MSS。结论免疫组化检测MLH1、MSH2、MSH6和PMS2的缺失可以用于Lynch综合征的初筛,对结直肠癌患者行MMR免疫组化检测和MSI联合检测可提高Lynch综合征的诊断率。     

新疆地区2718例子宫内膜癌构成及临床病理特征

目的 探讨新疆地区子宫内膜癌(endometrial cancer, EC)的流行病学特点及不同方法检测微卫星稳定性结果存在差异的原因。方法 收集2011～2021年2 718例EC流行病学资料，采用免疫组化EnVision法检测4种错配修复(mismatch repair, MMR)蛋白表达，分析其与临床病理特征的关系；采用多重荧光PCR-毛细管电泳法检测微卫星不稳定(microsatellite instability, MSI)的一致性，分析两种检测结果不一致的原因。结果 2 718例EC好发于51～60岁，11年间患者平均年龄和中位年龄分别下降1.3、3岁；组织学类型以子宫内膜样癌G1级为主，其他类型较少见。MMR蛋白表达总缺失率为24.2%,其中MLH1、MSH2、MSH6和PMS2表达缺失率分别为12.7%、5.5%、6.9%和15.2%;dMMR组与pMMR组在患者年龄、组织学类型、FIGO分期、脉管内瘤栓及淋巴结转移等参数，差异均有统计学意义(P<0.05);MSH2在维吾尔族和哈萨克族中缺失比例最高，MSH6缺失易发生于>50岁(P=0.033)、维吾尔族...     

126例子宫内膜癌中Lynch综合征的初步筛查

目的探讨hMSH2、hMSH6、hMLH1、hPMS2蛋白缺失情况和hMLH1基因启动子甲基化状态及Lynch综合征患者的家系分析,初步进行Lynch综合征相关子宫内膜癌筛查。方法采用免疫组化SP法检测126例子宫内膜癌中hMSH2、hMSH6、hMLH1、hPMS2蛋白表达,并用甲基化特异性PCR检测hMLH1蛋白表达缺失病例的hMLH1基因启动子甲基化状态。结果免疫组化结果显示22%(28/126)的病例出现MMR蛋白缺失表达,其中12例hMLH1~-/hPMS2~-、6例hPMS2~-、4例hMSH2~-/hMSH6~-,hMSH6~-和hMLH1~-各3例,以hMLH1和hPMS2蛋白缺失表达为主。甲基化特异性PCR检测有hMLH1蛋白表达缺失的15例子宫内膜癌中hMLH1基因启动子甲基化状态,证实9例存在hMLH1基因启动子甲基化,提示其为子宫内膜癌的散发性病例。结论对子宫内膜癌患者行MMR蛋白免疫组化SP法染色,结合甲基化特异性PCR检测hMLH1基因启动子甲基化状态,是初步筛查Lynch综合征的有效策略。     

Role of endometrial cancer abnormal MMR protein in screening Lynch-syndrome families

Objective: To identify patients with endometrial cancer with potential Lynch-related DNA mismatch repair (MMR) protein expression defects and to explore the role of these defects in screening for LS. Methods: Endometrial cancers from 173 patients recruited to the Nanchong Central Hospital were tested for MMR (MLH1, MSH2, PMS2, and MSH6) protein expression using immunohistochemistry (IHC). Results: In the 173 tumor tissue samples, the expression loss rates of MSH6, MSH2, PMS2 and MLH1 protein were 16.18% (28/173), 12.14% (21/173), 7.51% (13/173) and 5.78% (10/173), respectively. The total loss rate of MMR protein was 29.89% (27/87). There were 19 patients with a family history of cancer, of which 18 patients demonstrated loss of expression of MMR protein. In the 22 abnormal MMR patients without family history, five families were found to have Lynch-associated cancer (colorectal cancer, endometrial cancer, ovarian cancer, stomach cancer) after follow-up for two years. Conclusion: MMR proteins play an important role in the progress of endometrial cancer. The routine testing of MMR proteins in endometrial cancer can contribute to the screening of LS families, especially small families.     

Protein expression profiles of deoxyribonucleic acid mismatch repair genes: Association with clinicopathological characteristics of Malaysian Lynch syndrome patients

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, accounts for approximately 1–5% of all colorectal cancers. Germline mutations in a group of deoxyribonucleic acid (DNA) mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS1, and PMS2) are responsible for Lynch syndrome cases. This study focuses on the determination of MMR (MLH1, MSH2, MSH6, and PMS2) protein expression profile by immunohistochemical analysis and its association with clinicopathological characteristics in clinically diagnosed Malaysian Lynch syndrome patients. Fifty patients who fulfilled any of the revised Bethesda Guidelines criteria were recruited from four collaborating centers in Malaysia. Clinicopathological information of clinically diagnosed Lynch syndrome cases that underwent bowel resection was reviewed. Immunohistochemical analysis for MLH1, MSH2, MSH6, and PMS2 proteins were performed on paraffin-embedded carcinomatous tissues. Colorectal cancer protein expression analysis for MLH1, MSH2, MSH6, and PMS2 antigens showed absence of expression of any MMR proteins in 18 out of 50 clinically diagnosed Lynch syndrome patients (36.0%). There was a significant association between abnormal MMR protein expression with tumor size (p = 0.012), histological differentiation of cancers (p = 0.012), and growth pattern of tumor (p = 0.01). Abnormal expression of MMR protein in colorectal cancers in clinically diagnosed Lynch syndrome patients was associated with specific clinicopathological characteristics such as tumor size, histological differentiation of cancers, and growth pattern of tumor. Immunohistochemical analysis proved to be an advantageous pre-screening tool for Lynch syndrome in Malaysian patients and highly predictive of a germline mutation in DNA MMR genes.     

Markers of proliferative activity are predictors of patient outcome for low-grade endometrioid adenocarcinoma but not papillary serous carcinoma of endometrium.

On the basis of pathogenesis, two types of endometrial cancer can be recognized. Type 1 endometrial carcinomas are relatively indolent tumors that develop after prolonged estrogen stimulation, on a background of endometrial hyperplasia. Type 2 endometrial carcinomas are aggressive tumors that are not associated with hyperplasia or estrogen excess. The aim of this study is to evaluate the prognostic significance of tumor proliferative activity in early-stage endometrial cancer by using mitotic index and immunostaining, comparing Type 1 (endometrioid) and Type 2 (papillary serous carcinoma) tumors. The mitotic index, MIB-1, and p53 immunostaining in 39 tumors from patients with low-grade Stage Ia or Ib endometrioid adenocarcinoma; as well as 23 tumors from patients with Stage I papillary serous carcinoma. In low-grade endometrioid adenocarcinoma, mitotic and MIB-1 indices were statistically significant independent prognostic indicators (P =.004 and P =.018, respectively), and both were strongly correlated with p53 expression (P =.01 and P =.006, respectively). The mean mitotic index was 5 mitoses/10 high-power fields, and mean MIB-1 index was 27.5%. There was no significant correlation between mitotic or MIB-1 indices and patient outcome or p53 expression in papillary serous carcinoma. The mean mitotic index was 31 mitoses/10 high-power fields, and mean MIB-1 index was 30.5% in these tumors. p53 expression and proliferative indices are strongly correlated in low-grade endometrioid adenocarcinoma. MIB-1 and mitotic indices are independent prognostic indicators in these tumors. Papillary serous carcinoma of endometrium is rapidly proliferative in tumors even at an early stage, and quantification of proliferative activity in these tumors does not allow prediction of patient outcome.     

EphA2及其配体在子宫内膜样腺癌中的表达及其与血管生成的关系

 目的： 探讨生促红素肝细胞受体A2 （EphA2）及其配体ephrin-A1在子宫内膜样腺癌组织中的表达及其与肿瘤血管生成的关系。方法： 利用免疫组织化学法检测56例子宫内膜样腺癌、20例子宫内膜增生过长、30例正常子宫内膜增殖期和30例分泌期组织中EphA2、ephrin-A1、雌激素受体（ER）和孕激素受体（PR）的表达,并采用CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)。分析EphA2和ephrin-A1的表达与MVD之间的相关性及其与子宫内膜样腺癌临床病理特征的关系。结果： 子宫内膜样腺癌组织中EphA2和ephrin-A1的表达显著高于子宫内膜样增生过长及正常子宫内膜(P<0.05);EphA2和ephrin-A1表达水平及MVD值与子宫内膜样腺癌FIGO分期、肿瘤分化程度、肌层浸润深度、淋巴微血管浸润和孕激素受体表达有关(P<0.05);Spearman等级相关分析表明EphA2和ephrin-A1表达分别与MVD呈显著正相关(r=0.476,P<0.05;r=0.501,P<0.05)。结论： EphA2及其配体ephrin-A1在子宫内膜样腺癌中高表达,可能参与了肿瘤血管生成和孕激素抵抗。     

Evidence for breast cancer as an integral part of Lynch syndrome

Lynch syndrome, an autosomal dominant cancer predisposition caused by mutations in DNA mismatch repair (MMR) genes, mainly mainly mutL homolog 1, OMIM 120436 (MLH1) and mutS homolog 2, OMIM 609309 (MSH2), encompasses a tumor spectrum including primarily gastrointestinal, endometrial, and ovarian cancer. This study aimed at clarifying the heavily debated issue of breast cancer being part of Lynch syndrome. Detailed clinical data on cancer occurrence in Swiss female MLH1/MSH2 mutation carriers were gathered, all available breast cancer specimens assessed for molecular evidence for MMR deficiency (i.e., microsatellite instability (MSI), MMR protein expression, and somatic (epi)genetic MMR gene alterations) and compiled with the scarce molecular data available from the literature. Seventy unrelated Swiss Lynch syndrome families were investigated comprising 632 female family members at risk of which 92 were genetically verified mutation carriers (52 MLH1 and 40 MSH2). On contrast to endometrial and ovarian cancer, which occurred significantly more often and at younger age in MLH1/MSH2 mutation carriers (median 50.5 and 49.0 years; P < 0.00001), overall cumulative breast cancer incidence closely mirrored the one in the Swiss population (56.5 years). Six (85.7%) of seven breast cancer specimens available for molecular investigations displayed the hallmarks of MMR deficiency. Combined with data from the literature, MSI was present in 26 (70.3%) of 37 and altered MMR protein expression in 16 (72.7%) of 22 breast cancer specimens from MLH1/MSH2 mutation carriers. These findings, thus, provide strong molecular evidence for a pivotal role of MMR deficiency in breast cancer development in Lynch syndrome.     

MMP-14和c-myc基因在乳腺癌组织中表达及临床意义

目的分析乳腺癌病灶组织中基质金属蛋白酶(MMP)-14和c-myc原癌基因的表达活性,并探讨其与肿瘤临床特征和生存预后的关系,为乳腺癌的发生及靶向治疗提供理论依据。方法选择经手术切除获得病理组织确诊为乳腺癌患者共90例,年龄38~78岁,平均年龄53.6岁。对每例患者分别完整切除肿瘤组织和至少距离肿瘤切缘3 cm的正常乳腺组织,以免疫组织化学法半定量检测MMP-14蛋白,荧光原位杂交技术(FISH)检测组织c-myc基因扩增阳性率,进一步比较MMP-14蛋白和c-myc基因阳性与阴性表达者在不同肿瘤临床特征(包括年龄、肿瘤直径、临床分期、病理分级、淋巴结转移)中的差异,分析MMP-14蛋白和c-myc基因表达间的相关性;随访1~5年,比较MMP-14蛋白和c-myc基因阳性与阴性表达者的无瘤生存期、复发率和总生存率的差异性。结果每例患者均至少获得1份可有效分析的癌组织和癌旁正常组织。结果发现,癌组织MMP-14蛋白和c-myc基因表达阳性率显著高于癌旁正常组织(χ^2=40.000、31.358,P<0.05)。对MMP-14蛋白和c-myc基因在不同肿瘤临床特征的样本中进行分析发现,肿瘤直径越大、临床分期越晚、病理分级越低和伴淋巴结转移者的MMP-14蛋白、c-myc基因阳性表达越明显(P<0.05),但与年龄无关(P>0.05)。MMP-14蛋白阳性表达者的c-myc基因表达阳性率高于MMP-14蛋白阴性者,而c-myc基因阳性表达者的MMP-14蛋白表达阳性率高于c-myc基因阴性者(χ^2=4.160,P<0.05)。随访发现,MMP-14蛋白和c-myc基因阳性表达患者的无瘤生存期较阴性者显著缩短(P<0.05),复发率和总生存率比较,差异无统计学意义(P>0.05)。结论MMP-14蛋白和c-myc基因可广泛存在乳腺癌病灶组织中并被稳定检测出,表达上调可能参与乳腺癌的发生机制,并且在不同的肿瘤临床特征和生存预后结局患者中可检测出差异性表达,对早期诊断乳腺癌或作为肿瘤的敏感标志物有一定的应用潜力。     

DNA错配修复蛋白(MLH1,PMS2,MSH2,MSH6)与人类神经管畸形(NTDs)关联性的初步研究

目的通过观察神经管畸形(Neural Tube Defects,NTDs)患儿与正常胎儿脑组织中DNA错配修复(mis-match repair,MMR)蛋白MLH1、PMS2、MSH2及MSH6的表达情况,探讨MMR系统与NTDs发生机理间可能存在的联系。方法 NTDs患儿脑组织及正常胎儿脑组织各15例,运用免疫组化方法检测各病例中MLH1、PMS2、MSH2及MSH6蛋白表达情况。结果 NTDs组MLH1阳性率中位数为1.44%,正常组为(41.96±11.01)%,中位数为43.95%;NTDs组PMS2阳性率为(25.48±16.46)%;正常组为(43.36±7.86)%。NTDs组中两种蛋白较正常组明显下降,组间存在统计学差异(P0.01)。但NTDs组中MSH2及MSH6阳性率分别为(43.56±18.67)%、(32.26±23.18)%;正常组中为(45.87±8.49)%、(35.15±10.68)%。两种蛋白组间比较无统计学差异,P值分别为0.6516和0.5387。结论首次报道NTDs中可能存在一种或多种特定MMR蛋白表达异常,推测MMR系统表达异常可能在NTDs发生过程中起到重要作用。