Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, 1873 Rama IV Road, Pathumwan, Bangkok, 10330, Thailand.
The Queen Sirikit Center for Breast Cancer, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, 10330, Thailand.
Sci Rep. 2021 Jan 13;11(1):915. doi: 10.1038/s41598-020-79622-2.
Although mammograms play a key role in early breast cancer detection, the test is not applicable to all women, for example, women under the age of 40. The development of a noninvasive blood test with high sensitivity and accessibility will improve the effectiveness of breast cancer screening programmes. Secretory factors released from cancer cells can induce the expression of certain genes in a large number of white blood cells (WBCs). Therefore, cancer-dependent proteins in WBCs can be used as tumour markers with high sensitivity. Five proteins (LMAN1, AZI2, STAU2, MMP9 and PLOD1) from a systemic analysis of a variety of array data of breast cancer patients were subjected to immunofluorescence staining to evaluate the presence of fixed WBCs on 96-well plates from 363 healthy females and 358 female breast cancer patients. The results revealed that the average fluorescence intensity of anti-STAU2 and the percentage of STAU2-positive T and B lymphocytes in breast cancer patients (110.50 ± 23.38 and 61.87 ± 12.44, respectively) were significantly increased compared with those in healthy females (56.47 ± 32.03 and 33.02 ± 18.10, respectively) (p = 3.56 × 10, odds ratio = 24.59, 95% CI = 16.64-36.34). The effect of secreted molecules from breast cancer cells was proven by the increase in STAU2 intensity in PBMCs cocultured with MCF-7 and T47D cells at 48 h (p = 0.0289). The test demonstrated 98.32%, 82.96%, and 48.32% sensitivity and 56.47%, 83.47%, and 98.62% specificity in correlation with the percentage of STAU2-positive cells at 40, 53.34 and 63.38, respectively. We also demonstrated how to use the STAU2 test for the assessment of risk in women under the age of 40. STAU2 is a novel breast cancer marker that can be assessed by quantitative immunofluorescence staining of fixed WBCs that are transportable at room temperature via mail, representing a useful risk assessment tool for women without access to mammograms.
尽管乳腺 X 线摄影在早期乳腺癌检测中发挥着关键作用，但该检测并不适用于所有女性，例如 40 岁以下的女性。开发一种具有高灵敏度和可及性的非侵入性血液检测将提高乳腺癌筛查计划的效果。癌细胞释放的分泌因子可诱导大量白细胞（WBC）中某些基因的表达。因此，WBC 中的癌症相关蛋白可用作具有高灵敏度的肿瘤标志物。从对各种乳腺癌患者阵列数据的系统分析中选择了 5 种蛋白（LMAN1、AZI2、STAU2、MMP9 和 PLOD1），并通过免疫荧光染色来评估 363 名健康女性和 358 名女性乳腺癌患者 96 孔板上固定 WBC 的存在。结果表明，与健康女性（56.47 ± 32.03 和 33.02 ± 18.10）相比，乳腺癌患者的抗 STAU2 平均荧光强度和 STAU2 阳性 T 和 B 淋巴细胞的百分比（分别为 110.50 ± 23.38 和 61.87 ± 12.44）均显著增加（p = 3.56 × 10，优势比= 24.59，95%CI = 16.64-36.34）。在 MCF-7 和 T47D 细胞共培养的 PBMCs 中 STAU2 强度的增加证明了乳腺癌细胞分泌分子的作用（p = 0.0289）。该测试在与 STAU2 阳性细胞百分比分别为 40、53.34 和 63.38 相关时，在灵敏度方面分别达到了 98.32%、82.96%和 48.32%，在特异性方面分别达到了 56.47%、83.47%和 98.62%。我们还展示了如何使用 STAU2 测试来评估 40 岁以下女性的风险。STAU2 是一种新型乳腺癌标志物，可通过定量免疫荧光染色固定的白细胞进行评估，白细胞在室温下可通过邮件运输，代表了一种有用的风险评估工具，适用于无法进行乳腺 X 线摄影的女性。
