Marinović Sonja, Vuković Kristina, Škrtić Anita, Poljak Mirko, Petek Sara, Petek Lara, Kapitanović Sanja
Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruder Boskovic Institute, 10000 Zagreb, Croatia.
Department of Pathology, Clinical Hospital Merkur, 10000 Zagreb, Croatia.
Oncol Lett. 2021 Feb;21(2):131. doi: 10.3892/ol.2020.12392. Epub 2020 Dec 18.
Epidermal growth factor receptor (EGFR) expression is commonly upregulated in sporadic colorectal cancer (CRC) and its high expression is associated with poor prognosis in patients with CRC. CA-SSR1 is a dinucleotide CA repeat of the gene that can modulate transcription and is a potential target of the mismatch repair machinery in tumours with microsatellite instability (MSI). In the present study, 160 sporadic colon cancer samples were analysed for CA-SSR1 polymorphism and MSI status. Additionally, mRNA and protein expression levels in the tumour centre and in the invasive tumour front, compared with those in adjacent normal tissue samples, were evaluated in 80 tumour samples. An inverse association was identified between mRNA levels and the sum of repeats in both alleles of the CA-SSR1 polymorphism in normal tissues. Changes in CA-SSR1 were detected in the tumour centre as well as in the invasive tumour front and metastases in all MSI high (MSI-H) tumours. Analysis of EGFR expression at the mRNA and protein levels according to MSI status revealed lower mRNA and protein expression in MSI-H tumours than microsatellite-stable (MSS) tumours. Furthermore, higher EGFR levels in the invasive tumour front compared with in the tumour centre in MSS tumours were identified, suggesting a role of EGFR in tumour progression and higher invasive potential of MSS than MSI-H tumours.
表皮生长因子受体（EGFR）表达在散发性结直肠癌（CRC）中通常上调，其高表达与CRC患者的不良预后相关。CA-SSR1是该基因的二核苷酸CA重复序列，可调节转录，是微卫星不稳定（MSI）肿瘤中错配修复机制的潜在靶点。在本研究中，对160份散发性结肠癌样本进行了CA-SSR1多态性和MSI状态分析。此外，在80份肿瘤样本中评估了肿瘤中心和肿瘤浸润前沿与相邻正常组织样本相比的mRNA和蛋白表达水平。在正常组织中，mRNA水平与CA-SSR1多态性两个等位基因重复序列总和之间存在负相关。在所有MSI高（MSI-H）肿瘤的肿瘤中心、肿瘤浸润前沿和转移灶中均检测到CA-SSR1的变化。根据MSI状态对EGFR表达进行mRNA和蛋白水平分析，结果显示MSI-H肿瘤中的mRNA和蛋白表达低于微卫星稳定（MSS）肿瘤。此外，在MSS肿瘤中，肿瘤浸润前沿的EGFR水平高于肿瘤中心，这表明EGFR在肿瘤进展中起作用，且MSS肿瘤的侵袭潜力高于MSI-H肿瘤。
