Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Iran Biomed J. 2023 Mar 1;27(2 & 3):126-35. doi: 10.61186/ibj.3857.
K-Ras mutations rarely occur in breast cancer. However, studies have supported that K-Ras upregulation is involved in breast cancer pathogenesis. Two main K-Ras transcript variants; K-Ras4A and K-Ras4B, originate from the alternative splicing of exon 4. In this study, we aimed to evaluate variations in the expression of K-Ras4A and K-Ras4B and their role in breast ductal carcinoma.
Total RNA was extracted from breast tumors, and the NATs obtained via mastectomy. Patients were selected from new cases of breast cancer with no prior history of chemotherapy. Relative mRNA expression was calculated based on a pairwise comparison between the tumors and the NATs following normalization to the internal control gene. Predictive values of the transcript variants were examined by ROC curve analysis.
A statistically significant increase was found in the K-Ras4A and K-Ras4B expression with the mean fold changes of 7.58 (p = 0.01) and 2.47 (p = 0.001), respectively. The K-Ras4A/K-Ras4B ratio was lower in the tumors than that of the normal tissues. ROC curve analysis revealed the potential of K-Ras4A (AUC: 0.769) and K-Ras4B (AUC: 0.688) in breast cancer prediction. There was also a significant association between K-Ras4B expression and HER2 statues (p = 0.04). Furthermore, a significant link was detected between K-Ras4A expression and pathological prognostic stages (p = 0.04).
Our findings revealed that expression levels of K-Ras4A and K-Ras4B is higher in the tumor compared to the normal breast tissues. Increase in K-Ras4A expression was more significant than that of K-Ras4B.
K-Ras 突变在乳腺癌中很少发生。然而，研究表明 K-Ras 的上调参与了乳腺癌的发病机制。两个主要的 K-Ras 转录变体；K-Ras4A 和 K-Ras4B，来源于外显子 4 的选择性剪接。在这项研究中，我们旨在评估 K-Ras4A 和 K-Ras4B 的表达变化及其在乳腺导管癌中的作用。
从乳房肿瘤和乳房切除术获得的 NAT 中提取总 RNA。患者从无化疗史的新乳腺癌病例中选择。通过将肿瘤与 NAT 之间的相对 mRNA 表达基于内部对照基因进行归一化，计算相对 mRNA 表达。通过 ROC 曲线分析检查转录变体的预测值。
发现 K-Ras4A 和 K-Ras4B 的表达均显著增加，平均倍数变化分别为 7.58（p = 0.01）和 2.47（p = 0.001）。肿瘤中的 K-Ras4A/K-Ras4B 比值低于正常组织。ROC 曲线分析显示 K-Ras4A（AUC：0.769）和 K-Ras4B（AUC：0.688）在乳腺癌预测中的潜力。K-Ras4B 表达与 HER2 状态之间也存在显著关联（p = 0.04）。此外，还检测到 K-Ras4A 表达与病理预后分期之间存在显著关联（p = 0.04）。
我们的研究结果表明，与正常乳腺组织相比，肿瘤中 K-Ras4A 和 K-Ras4B 的表达水平更高。K-Ras4A 表达的增加比 K-Ras4B 更显著。
