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评估CDX2表达免疫组化评分系统作为结肠癌预后生物标志物的研究

Evaluation of the Immunohistochemical Scoring System of CDX2 Expression as a Prognostic Biomarker in Colon Cancer.

作者信息

Ilie-Petrov Andreea-Corina, Cristian Daniel-Alin, Grama Florin Andrei, Chitul Andrei, Blajin Angela, Popa Andrei, Mandi Draga-Maria, Welt Luminița, Bara Marina Alina, Vrîncianu Rareș, Ardeleanu Carmen Maria

机构信息

Faculty of Medicine, "Carol Davila" University of Medicine and Pharmacy, 020021 Bucharest, Romania.

Clinical General Surgery Department, Colțea Clinical Hospital, 030171 Bucharest, Romania.

出版信息

Diagnostics (Basel). 2024 May 15;14(10):1023. doi: 10.3390/diagnostics14101023.

Abstract

Encoded by the CDX2 homeobox gene, the CDX2 protein assumes the role of a pivotal transcription factor localized within the nucleus of intestinal epithelial cells, orchestrating the delicate equilibrium of intestinal physiology while intricately guiding the precise development and differentiation of epithelial tissue. Emerging research has unveiled that positive immunohistochemical expression of this protein shows that the CDX2 gene exerts a potent suppressive impact on tumor advancement in colorectal cancer, impeding the proliferation and distant dissemination of tumor cells, while the inhibition or suppression of CDX2 frequently correlates with aggressive behavior in colorectal cancer. In this study, we conducted an immunohistochemical assessment of CDX2 expression on a cohort of 43 intraoperatively obtained tumor specimens from patients diagnosed with colon cancer at Colțea Clinical Hospital in Bucharest, between April 2019 and December 2023. Additionally, we shed light on the morphological diversity within colon tumors, uncovering varying differentiation grades within the same tumor, reflecting the variations in CDX2 expression as well as the genetic complexity underlying these tumors. Based on the findings, we developed an innovative immunohistochemical scoring system that addresses the heterogeneous nature of colon tumors. Comprehensive statistical analysis of CDX2 immunohistochemical expression unveiled significant correlations with known histopathological parameters such as tumor differentiation grades (-value = 0.011) and tumor budding score (-value = 0.002), providing intriguing insights into the complex involvement of the CDX2 gene in orchestrating tumor progression through modulation of differentiation processes, and highlighting its role in metastatic predisposition. The compelling correlation identified between CDX2 expression and conventional histopathological parameters emphasizes the prognostic significance of the CDX2 biomarker in colon cancer. Moreover, our novel immunohistochemical scoring system reveals a distinct subset of colon tumors exhibiting reserved prognostic outcomes, distinguished by their "mosaic" CDX2 expression pattern.

摘要

CDX2蛋白由CDX2同源框基因编码,是一种关键的转录因子,定位于肠道上皮细胞核内,在协调肠道生理的微妙平衡的同时,精确指导上皮组织的发育和分化。新兴研究表明,该蛋白的阳性免疫组化表达显示CDX2基因对结直肠癌的肿瘤进展具有强大的抑制作用,可阻碍肿瘤细胞的增殖和远处扩散,而CDX2的抑制或缺失通常与结直肠癌的侵袭性行为相关。在本研究中,我们对2019年4月至2023年12月期间在布加勒斯特科尔泰亚临床医院诊断为结肠癌的患者术中获取的43例肿瘤标本进行了CDX2表达的免疫组化评估。此外,我们还揭示了结肠肿瘤内的形态学多样性,发现同一肿瘤内存在不同的分化程度,反映了CDX2表达的差异以及这些肿瘤潜在的遗传复杂性。基于这些发现,我们开发了一种创新的免疫组化评分系统,以应对结肠肿瘤的异质性。对CDX2免疫组化表达的综合统计分析揭示了与已知组织病理学参数如肿瘤分化程度(P值=0.011)和肿瘤芽生评分(P值=0.002)之间的显著相关性,为CDX2基因通过调节分化过程协调肿瘤进展的复杂机制提供了有趣的见解,并突出了其在转移易感性中的作用。CDX2表达与传统组织病理学参数之间的显著相关性强调了CDX2生物标志物在结肠癌中的预后意义。此外,我们新颖的免疫组化评分系统揭示了一组具有独特预后结果的结肠肿瘤亚群,其特征是“镶嵌”CDX2表达模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3503/11119288/03fe45025c95/diagnostics-14-01023-g001.jpg

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