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SATB2 和 CDX2 表达缺失与结直肠癌中 DNA 错配修复蛋白缺陷和 BRAF 突变相关。

Loss of SATB2 and CDX2 expression is associated with DNA mismatch repair protein deficiency and BRAF mutation in colorectal cancer.

机构信息

Department of Pathology, Fujian Provincial Hospital, Fuzhou, 350001, China.

Department of Pathology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350004, China.

出版信息

Med Mol Morphol. 2024 Mar;57(1):1-10. doi: 10.1007/s00795-023-00366-9. Epub 2023 Aug 15.

DOI:10.1007/s00795-023-00366-9
PMID:37583001
Abstract

The relationship between the expression of the SATB2 and CDX2 proteins and common molecular changes and clinical prognosis in colorectal cancer (CRC) still needs further clarification. We collected 1180 cases of CRC and explored the association between the expression of SATB2 and CDX2 and clinicopathological characteristics, molecular alterations, and overall survival of CRC using whole-slide immunohistochemistry. Our results showed that negative expression of SATB2 and CDX2 was more common in MMR-protein-deficient CRC than in MMR-protein-proficient CRC (15.8% vs. 6.0%, P = 0.001; 14.5% vs. 4.0%, P = 0.000, respectively). Negative expression of SATB2 and CDX2 was more common in BRAF-mutant CRC than in BRAF wild-type CRC (17.2% vs. 6.1%, P = 0.003; 13.8% vs. 4. 2%; P = 0.004, respectively). There was no relationship between SATB2 and/or CDX2 negative expression and KRAS, NRAS, and PIK3CA mutations. The lack of expression of SATB2 and CDX2 was associated with poor histopathological features of CRC. In multivariate analysis, negative expression of SATB2 (P = 0.030), negative expression of CDX2 (P = 0.043) and late clinical stage (P = 0.000) were associated with decreased overall survival of CRC. In conclusion, the lack of SATB2 and CDX2 expression in CRC was associated with MMR protein deficiency and BRAF mutation, but not with KRAS, NRAS and PIK3CA mutation. SATB2 and CDX2 are prognostic biomarkers in patients with CRC.

摘要

SATB2 和 CDX2 蛋白的表达与结直肠癌(CRC)常见的分子改变和临床预后之间的关系仍需要进一步阐明。我们收集了 1180 例 CRC 病例,并通过全切片免疫组织化学法研究了 SATB2 和 CDX2 的表达与 CRC 的临床病理特征、分子改变和总生存之间的关系。结果显示,SATB2 和 CDX2 阴性表达在错配修复蛋白缺陷型 CRC 中比在错配修复蛋白功能正常型 CRC 中更为常见(15.8%比 6.0%,P=0.001;14.5%比 4.0%,P=0.000)。SATB2 和 CDX2 阴性表达在 BRAF 突变型 CRC 中比在 BRAF 野生型 CRC 中更为常见(17.2%比 6.1%,P=0.003;13.8%比 4.2%,P=0.004)。SATB2 和/或 CDX2 阴性表达与 KRAS、NRAS 和 PIK3CA 突变之间无相关性。SATB2 和 CDX2 表达缺失与 CRC 的不良组织学特征相关。多因素分析显示,SATB2 阴性表达(P=0.030)、CDX2 阴性表达(P=0.043)和晚期临床分期(P=0.000)与 CRC 总生存时间缩短相关。结论:CRC 中 SATB2 和 CDX2 的表达缺失与 MMR 蛋白缺失和 BRAF 突变有关,而与 KRAS、NRAS 和 PIK3CA 突变无关。SATB2 和 CDX2 是 CRC 患者的预后生物标志物。

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本文引用的文献

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Cancers (Basel). 2021 Dec 7;13(24):6177. doi: 10.3390/cancers13246177.
2
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Curr Oncol. 2021 Dec 13;28(6):5356-5383. doi: 10.3390/curroncol28060447.
3
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Diseases. 2024 Oct 1;12(10):234. doi: 10.3390/diseases12100234.
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Am J Surg Pathol. 2019 Oct;43(10):1314-1322. doi: 10.1097/PAS.0000000000001330.
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Colitis-associated colorectal adenocarcinomas are frequently associated with non-intestinal mucin profiles and loss of SATB2 expression.结肠炎相关结直肠腺癌常伴有非肠道黏蛋白谱和 SATB2 表达缺失。
Mod Pathol. 2019 Jun;32(6):884-892. doi: 10.1038/s41379-018-0198-0. Epub 2019 Feb 1.
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