Mongkolwat Wariya, Sonthi Phattarapon, Somsuan Keerakarn, Aluksanasuwan Siripat, Samol Ratirath, Sakulsak Natthiya, Wanna-Udom Sasithorn
Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand.
Biomed Rep. 2025 May 16;23(1):119. doi: 10.3892/br.2025.1997. eCollection 2025 Jul.
The SWitch/sucrose non-fermentable chromatin remodeling complex functions as a tumor suppressor by regulating gene expression and thus various cellular processes. Key subunits of this complex, including the AT-rich interactive domain (ARID)-containing proteins ARID1A, ARID1B and ARID2, are frequently mutated in cancer, including colorectal cancer (CRC). However, their protein expression and prognostic significance in CRC remain unclear. The present study investigated the ARID1A, ARID1B and ARID2 expression levels in CRC tissues and their relationship with the clinicopathological characteristics of patients. Bioinformatics analysis of The Cancer Genome Atlas-colon adenocarcinoma cohort revealed frequent mutations, positive mRNA correlations among the genes and increased promoter methylation levels. Immunohistochemical analysis of 63 CRC tissue samples demonstrated significantly decreased ARID1A, ARID1B and ARID2 protein expression in cancerous areas compared with adjacent non-cancerous areas of the tissues. Low ARID1A and ARID1B expression levels were significantly associated with advanced clinicopathological characteristics in Thai patients with CRC. All three ARIDs showed a trend towards an association with the 5-year progression-free survival of Thai patients with CRC. Kaplan-Meier plotter database analysis further demonstrated that low expression of all three genes was associated with a shorter overall survival time in patients with CRC; however, only expression showed a statistically significant prognostic relevance. In conclusion, the ARID1A, ARID1B and ARID2 expression levels were shown to be positively correlated, and their reduced expression was associated with worse clinicopathological characteristics in patients with CRC. These findings suggest the potential of ARIDs as prognostic biomarkers, warranting further investigation to validate their clinical significance.
SWI/SNF染色质重塑复合体通过调节基因表达进而调控各种细胞过程发挥肿瘤抑制作用。该复合体的关键亚基，包括富含AT互作结构域（ARID）的蛋白ARID1A、ARID1B和ARID2，在包括结直肠癌（CRC）在内的多种癌症中经常发生突变。然而，它们在CRC中的蛋白表达及预后意义仍不明确。本研究调查了CRC组织中ARID1A、ARID1B和ARID2的表达水平及其与患者临床病理特征的关系。对癌症基因组图谱-结肠腺癌队列的生物信息学分析显示存在频繁突变、基因间mRNA正相关以及启动子甲基化水平升高。对63例CRC组织样本的免疫组化分析表明，与组织的相邻非癌区域相比，癌区中ARID1A、ARID1B和ARID2蛋白表达显著降低。在泰国CRC患者中，低ARID1A和ARID1B表达水平与晚期临床病理特征显著相关。所有三种ARID均显示出与泰国CRC患者5年无进展生存期相关的趋势。Kaplan-Meier绘图仪数据库分析进一步表明，所有这三个基因低表达均与CRC患者较短的总生存时间相关；然而，只有 表达显示出具有统计学意义的预后相关性。总之，ARID1A、ARID1B和ARID2的表达水平呈正相关，其表达降低与CRC患者较差的临床病理特征相关。这些发现提示ARID作为预后生物标志物的潜力，值得进一步研究以验证其临床意义。
