Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.
Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.
Iran Biomed J. 2022 Jan 1;26(1):53-63. doi: 10.52547/ibj.26.1.53.
Single nucleotide polymorphisms result in dysregulation of the proto-oncogene TCF3 gene, which is associated with the development, metastasis, and chemoresistance of different malignancies.
GSE10810 microarray dataset and GEPIA2 online software were used to find differentially expressed genes and the TCF3 status in breast cancer (BC) and gastric cancer (GC), respectively. Plots and figures of microarray analysis were prepared by ggplot2 and pheatmap packages. Differentially expressed genes were obtained by the Bioconductor limma package. In silico analysis was used to predict the functions of rs72618599. BC (n = 123), GC (n = 132) and healthy age and gender matched controls (n = 184) were genotyped, using the high-resolution melting technique.
Based on the allelic comparison study, C allele of rs72618599 was associated with the BC tumor stage IV (66.1%, 78/120, p < 0.0001) and grade III (52.4%, 55/72, p < 0.0001), while the T allele was associated with metastasis (84.2%, 10/162, p < 0.0001). However, in GC patients, the C allele was significantly correlated with H. pylori infection (51.7%, 30/58, p = 0.008), stage III of primary tumors (47.7%, 62/88, p = 0.017), stage II of lymph node status (35.5%, 44/74, p = 0.017), and metastasis (52.9%, 90/132, p = 0.044). In silico analysis predicted that rs72618599 leads to the creation of a binding site for hsa-miR526b-5p in the 3′-UTR of TCF3 transcript.
Regarding the rs72618599 SNP, the C allele, is associated with poor prognosis of BC and GC. Furthermore, rs72618599 may be associated with cancer progression by altering the regulatory affinity of hsa-miR526b-5p to 3′-UTR of TCF3.
单核苷酸多态性导致原癌基因 TCF3 基因失调，与不同恶性肿瘤的发生、转移和化疗耐药有关。
使用 GSE10810 微阵列数据集和 GEPIA2 在线软件分别在乳腺癌 (BC) 和胃癌 (GC) 中寻找差异表达基因和 TCF3 状态。通过 ggplot2 和 pheatmap 软件包绘制微阵列分析的图表和图形。通过 Bioconductor limma 软件包获得差异表达基因。通过计算生物学分析预测 rs72618599 的功能。对 123 例 BC、132 例 GC 和 184 例年龄和性别匹配的健康对照进行 rs72618599 的高分辨率熔解曲线分析。
基于等位基因比较研究，rs72618599 的 C 等位基因与 BC 肿瘤 IV 期 (66.1%，78/120，p < 0.0001) 和 III 级 (52.4%，55/72，p < 0.0001) 相关，而 T 等位基因与转移相关 (84.2%，162/10，p < 0.0001)。然而，在 GC 患者中，C 等位基因与 H. pylori 感染显著相关 (51.7%，30/58，p = 0.008)、原发肿瘤 III 期 (47.7%，62/88，p = 0.017)、淋巴结状态 II 期 (35.5%，44/74，p = 0.017) 和转移 (52.9%，90/132，p = 0.044)。计算生物学分析预测 rs72618599 导致 TCF3 转录本 3′-UTR 中 hsa-miR526b-5p 结合位点的产生。
关于 rs72618599 SNP，C 等位基因与 BC 和 GC 的不良预后相关。此外，rs72618599 可能通过改变 hsa-miR526b-5p 对 TCF3 3′-UTR 的调节亲和力与癌症进展相关。
