临床与病理杂志2024,Vol.44Issue(1) :14-22.DOI:10.11817/j.issn.2095-6959.2024.230425

SEPTIN9与HOXA9基因甲基化在鉴别阑尾和卵巢来源腹膜假黏液瘤中的诊断价值

Diagnostic value of SEPTIN9 and HOXA9 gene methylation in distinguishing appendiceal from ovarian pseudomyxoma peritonei

侯芳 卢一艳 齐长海 李方 任晓沙 佘彬
临床与病理杂志2024,Vol.44Issue(1) :14-22.DOI:10.11817/j.issn.2095-6959.2024.230425

SEPTIN9与HOXA9基因甲基化在鉴别阑尾和卵巢来源腹膜假黏液瘤中的诊断价值

Diagnostic value of SEPTIN9 and HOXA9 gene methylation in distinguishing appendiceal from ovarian pseudomyxoma peritonei

侯芳 1卢一艳 1齐长海 1李方 1任晓沙 2佘彬2
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作者信息

  • 1. 航天中心医院病理科,北京 100049
  • 2. 上海甲预生命科技有限公司,上海 201203
  • 折叠

摘要

目的:腹膜假黏液瘤(pseudomyxoma peritonei,PMP)是一种罕见的腹膜恶性肿瘤综合征,其来源鉴别较困难.本研究旨在探讨SEPTIN9与HOXA9基因在阑尾黏液性肿瘤来源的PMP(appendiceal mucinous neoplasms-PMP,AMNs-PMP)与卵巢黏液性肿瘤来源的PMP(ovarian mucinous tumors-PMP,OMTs-PMP)中的甲基化水平及其对PMP鉴别的意义.方法:采用甲基化特异度聚合酶链反应(methylation-specific polymerase chain reaction,MS-PCR)检测SEPTIN9与HOXA9基因在正常阑尾(appendix control,APD control)组(n=10)、正常卵巢(ovary control,OV control)组(n=17)、AMNs-PMP组(n=40)及OMTs-PMP组(n=19)中的甲基化水平,同时对AMNs-PMP组及OMTs-PMP组的组织样本进行细胞角蛋白(cytokeratin,CK)7、CK20免疫组织化学检测.通过t检验分析SEPTIN9及HOXA9基因甲基化在AMNs-PMP组及OMTs-PMP组中表达差异并分析其与免疫组织化学联合检测的作用及价值.结果:AMNs-PMP组中SEPTIN9基因甲基化的阳性率明显高于OMTs-PMP组(92.5%vs 63.2%,P<0.01);OMTs-PMP组中HOXA9基因甲基化的阳性率显著高于AMNs-PMP组(94.7%vs 12.5%,P<0.001).OMTs-PMP组中HOXA9基因甲基化的ΔCt值显著低于AMNs-PMP组(3.20±0.47 vs 8.63±0.61,P<0.001).OMTs-PMP组中CK7的阳性率显著高于AMNs-PMP组(94.7%vs 17.5%,P<0.001),AMNs-PMP组中CK20的阳性率显著高于OMTs-PMP组(97.5%vs 63.2%,P<0.001).CK7(-)CK20(+)与SEPTIN9(+)HOXA9(-)基因甲基化在AMNs-PMP中诊断均有较高的敏感度(82.5%vs 87.5%)和特异度(均为94.7%);CK7(+)CK20(-)与SEPTIN9(-)HOXA9(+)基因甲基化在OMTs-PMP诊断中均有较低的敏感度(均为36.8%)、较高的特异度(97.5%vs 92.5%),而CK7(+)HOXA9(+)在与前2种组合特异度相似的情况下,其敏感度为89.5%,显著高于前二者.结论:SEPTIN9(+)HOXA9(-)可用于AMNs-PMP诊断,CK7(+)HOXA9(+)可用于OMTs-PMP诊断.SEPTIN9与HOXA9基因甲基化可成为AMNs-PMP及OMTs-PMP的潜在生物学标志物.

Abstract

Objective:Pseudomyxoma peritonei(PMP)is a rare peritoneal malignant tumor syndrome,and its origin is difficult to distinguish.This study aims to explore the methylation levels of SEPTIN9 and HOXA9 genes in PMP originating from appendiceal mucinous neoplasms-PMP(AMNs-PMP)and ovarian mucinous tumors-PMP(OMTs-PMP),and their significance in distinguishing PMP.Methods:Methylation-specific polymerase chain reaction(MS-PCR)was used to detect the methylation levels of SEPTIN9 and HOXA9 genes in a normal appendix control group(APD control,n=10),a normal ovary control group(OV control,n=17),a AMNs-PMP group(n=40),and a OMTs-PMP group(n=19).Immunohistochemical detection of cytokeratin(CK)7 and CK20 was performed on tissue samples from the AMNs-PMP group and the OMTs-PMP group.The expression of SEPTIN9 and HOXA9 gene methylation in the AMNs-PMP group and the OMTs-PMP group was analyzed by t-test,and the role and value of combined immunohistochemical detection were analyzed.Results:The positivity rate of SEPTIN9 gene methylation in the AMNs-PMP group was significantly higher than that in the OMTs-PMP group(92.5%vs 63.2%,P<0.01).The positive rate of HOXA9 gene methylation in the OMTs-PMP group was significantly higher than that in the AMNs-PMP group(94.7%vs 12.5%,P<0.001).The ΔCt value of HOXA9 gene methylation in the OMTs-PMP group was significantly lower than that in the AMNs-PMP group(3.20±0.47 vs 8.63±0.61,P<0.001).The positivity rate of CK7 in the OMTs-PMP group was significantly higher than that in the AMNs-PMP group(94.7%vs 17.5%,P<0.001),whilie the positivity rate of CK20 in the AMNs-PMP group was significantly higher than that in the OMTs-PMP group(97.5%vs 63.2%,P<0.001).CK7(-)CK20(+)and SEPTIN9(+)HOXA9(-)gene methylation had high sensitivity(82.5%vs 87.5%)and specificity(both 94.7%)in diagnosing of AMNs-PMP.CK7(+)CK20(-)and SEPTIN9(-)HOXA9(+)gene methylation had low sensitivity(both 36.8%)and high specificity(97.5%vs 92.5%)in the diagnosing of OMTs-PMP.while CK7(+)HOXA9(+)had higher sensitivity(89.5%)than the previous 2 combinations with a similar specificity.Conclusion:Utilization of SEPTIN9(+)HOXA9(-)can be used for diagnosing AMNs-PMP,and CK7(+)HOXA9(+)can be used for diagnosing OMTs-PMP.Methylation of HOXA9 and SEPTIN9 genes can serve as potential biological markers for the differential diagnosis of AMNs-PMP and OMTs-PMP.

关键词

甲基化/表观遗传学/假黏液瘤/SEPTIN9/HOXA9

Key words

methylation/epigenetics/pseudomyxoma peritonei/SEPTIN9/HOXA9

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出版年

2024
临床与病理杂志
中南大学

临床与病理杂志

CSTPCD
影响因子:0.559
ISSN:1673-2588
参考文献量22
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