Division of Gastroenterology, Department of Internal Medicine, University Hospital of Split, Spinčićeva 1, 21000 Split, Croatia.
Department of Anatomy, Histology and Embryology, University of Split School of Medicine, Šoltanska 2, 21000 Split, Croatia.
Genes (Basel). 2023 Jun 21;14(7):1306. doi: 10.3390/genes14071306.
Left-sided and right-sided colorectal cancer (L-CRC and R-CRC) have relatively different clinical pictures and pathophysiological backgrounds. The aim of this study was to investigate the presence of DAB adapter protein 2 (DAB2) as a potential molecular mechanism that contributes to this diversity in terms of malignancy and responses to therapy. The expression of the suppressor gene DAB2 in colon cancer has already been analyzed, but its significance has not been fully elucidated. Archived samples from 34 patients who underwent colon cancer surgery were included in this study, with 13 patients with low-grade CRC and 21 with high-grade CRC. Twenty of the tumors were R-CRC, while 14 were L-CRC. DAB2 expression was analyzed immunohistochemically in the tumor tissue and the colon resection margin was used as a control. Tumors were divided into L-CRC and R-CRC, with splenic flexure as the cutoff point for each side. The results showed that R-CRC had lower DAB2 protein expression compared to L-CRC ( = 0.01). High-grade tumors had reduced DAB2 expression compared to low-grade tumors ( = 0.02). These results are consistent with the analysis of gene expression data that we exported from the TCGA Colon and Rectal Cancer Study (COADREAD). In 736 samples of colon cancer, lower gene expression was found in R-CRC compared to L-CRC ( < 0.0001). gene expression was significantly higher in the sigmoid colon than in the cecum and ascending colon ( < 0.01). The analysis confirmed a lower expression of the in tumors with positive microsatellite instability ( < 0.001). In conclusion, DAB2 has a role in the biological differences between R-CRC and L-CRC and its therapeutic and diagnostic potential needs to be further examined.
左侧和右侧结直肠癌(L-CRC 和 R-CRC)具有相对不同的临床特征和病理生理背景。本研究旨在探讨 DAB 衔接蛋白 2(DAB2)的存在是否是导致这种恶性程度和治疗反应多样性的潜在分子机制。已经分析了结直肠癌中抑制基因 DAB2 的表达,但尚未充分阐明其意义。本研究纳入了 34 例接受结肠癌手术的患者的存档样本,其中 13 例为低级别 CRC,21 例为高级别 CRC。20 例肿瘤为 R-CRC,14 例为 L-CRC。采用免疫组织化学方法分析肿瘤组织中 DAB2 的表达,以结肠切除边缘作为对照。将肿瘤分为 L-CRC 和 R-CRC,脾曲作为两侧的分界点。结果显示,R-CRC 的 DAB2 蛋白表达低于 L-CRC( = 0.01)。高级别肿瘤的 DAB2 表达低于低级别肿瘤( = 0.02)。这些结果与我们从 TCGA 结肠癌和直肠癌研究(COADREAD)导出的基因表达数据的分析一致。在 736 例结肠癌样本中,R-CRC 的 基因表达低于 L-CRC( < 0.0001)。在乙状结肠中,基因表达显著高于盲肠和升结肠( < 0.01)。分析证实,在微卫星不稳定阳性的肿瘤中,基因表达较低( < 0.001)。综上所述,DAB2 在 R-CRC 和 L-CRC 之间的生物学差异中起作用,其治疗和诊断潜力需要进一步研究。