Biochemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt.
Cancer Biomark. 2017;18(4):413-423. doi: 10.3233/CBM-160308.
We examined the expression status of p21^{Waf1/Cip1} and p57^{Kip2} in breast cancer as well as their relationship with clinicopathological factors. Moreover, the diagnostic value of gene promoter methylation of p21^Waf1/Cip1 and p57^Kip2 was assessed in breast cancer patients.
This study involved 85 patients diagnosed with breast cancer and 36 patients with benign breast lesions. The expression of p21^{Waf1/Cip1} and p57^{Kip2} in cell lysates was analyzed by ELISA and Western blot, respectively. The gene promoter methylation of p21^Waf1/Cip1 and p57^Kip2 was examined in cell lysates by methylation specific PCR.
p21^{Waf1/Cip1} expression was higher while p57^{Kip2} level was lower in breast cancer patients compared to patients with benign breast lesions. The combined use of p21^{Waf1/Cip1} and p57^{Kip2} provided sensitivity and specificity of 82.35% and 86.11%, respectively. None of the malignant and benign breast tumors were found to be hypermethylated at p21^Waf1/Cip1 gene promoter. However, aberrant methylation of p57^Kip2 gene promoter was detected in 49 of 85 (57.65%) of breast cancer tumors. High p21^{Waf1/Cip1} level was associated with high grade, late stages and lymph node involvement, whereas low p57^{Kip2} level was correlated with high grade and HER2 overexpressing breast cancer. Moreover, hypermethylated p57^Kip2 gene promoter was associated with high grade.
Our findings show that the overexpression of p21^{Waf1/Cip1}, down-expression of p57^{Kip2} and gene promoter methylation of p57^Kip2 could be considered as promising diagnostic markers for breast cancer.
研究 p21^Waf1/Cip1 和 p57^Kip2 在乳腺癌中的表达状态及其与临床病理因素的关系。此外，评估了 p21^Waf1/Cip1 和 p57^Kip2 基因启动子甲基化在乳腺癌患者中的诊断价值。
本研究共纳入 85 例乳腺癌患者和 36 例良性乳腺病变患者。通过 ELISA 和 Western blot 分别分析细胞裂解物中 p21^Waf1/Cip1 和 p57^Kip2 的表达。通过甲基化特异性 PCR 检测细胞裂解物中 p21^Waf1/Cip1 和 p57^Kip2 基因启动子的甲基化。
与良性乳腺病变患者相比，乳腺癌患者中 p21^Waf1/Cip1 的表达水平升高，而 p57^Kip2 的水平降低。联合使用 p21^Waf1/Cip1 和 p57^Kip2 的诊断敏感性和特异性分别为 82.35%和 86.11%。在所有恶性和良性乳腺肿瘤中均未发现 p21^Waf1/Cip1 基因启动子的异常高甲基化。然而，在 85 例乳腺癌肿瘤中有 49 例（57.65%）检测到 p57^Kip2 基因启动子的异常甲基化。高 p21^Waf1/Cip1 水平与高分级、晚期和淋巴结受累有关，而低 p57^Kip2 水平与高分级和 HER2 过表达乳腺癌有关。此外，p57^Kip2 基因启动子的高甲基化与高分级相关。
我们的研究结果表明，p21^Waf1/Cip1 的过表达、p57^Kip2 的下调以及 p57^Kip2 基因启动子的甲基化可以作为乳腺癌有前途的诊断标志物。
