Department of Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX.
Int J Cancer. 2014 Feb 1;134(3):587-95. doi: 10.1002/ijc.28389. Epub 2013 Sep 13.
A simple and accurate test to detect early-stage breast cancer has not been developed. Previous studies indicate that the level of human endogenous retrovirus type K (group HERV-K(HML-2)) transcription may be increased in human breast tumors. We hypothesized that HERV-K(HML-2) reactivation can serve as a biomarker for early detection of breast cancer. Serum samples were collected from women without cancer (controls) and patients with ductal carcinoma in situ (DCIS) and invasive breast cancer. ELISA assays were used to detect serum anti-HERV-K(HML-2) antibody titers. RNA was extracted from sera and analyzed by real-time RT-PCR to quantitate the level of HERV-K(HML-2) mRNA. We measured significantly higher serum mRNA and serum antibody titers against HERV-K(HML-2) proteins in women with DCIS and stage I disease than in women without cancer. At optimized cutoffs for the antibody titers, the assay produced an area under the receiver operating characteristic curve (AUC) of 0.89 (95% confidence interval 0.77-1.00) for DCIS and of 0.95 (95% confidence interval 0.89-1.00) for invasive breast cancer. These AUCs are comparable to those observed for mammograms. We also found that serum HERV-K(HML-2) mRNA tended to be higher in breast cancer patients with a primary tumor who later on developed the metastatic disease than in patients who did not develop cancer metastasis. Our results show that HERV-K(HML-2) antibodies and mRNA are already elevated in the blood at an early stage of breast cancer, and further increase in patients who are at risk of developing a metastatic disease.
一种简单而准确的早期乳腺癌检测方法尚未被开发出来。先前的研究表明，人类内源性逆转录病毒 K 型（组 HERV-K(HML-2)）转录水平可能在人类乳腺癌肿瘤中升高。我们假设 HERV-K(HML-2)的重新激活可以作为乳腺癌早期检测的生物标志物。从没有癌症的女性（对照组）和患有导管原位癌（DCIS）和浸润性乳腺癌的患者中采集血清样本。使用 ELISA 检测试剂盒检测血清抗 HERV-K(HML-2)抗体滴度。从血清中提取 RNA，并通过实时 RT-PCR 分析来定量 HERV-K(HML-2)mRNA 的水平。我们发现，患有 DCIS 和 I 期疾病的女性血清中 HERV-K(HML-2)mRNA 和针对 HERV-K(HML-2)蛋白的抗体滴度明显高于没有癌症的女性。在优化的抗体滴度截断值下，该检测方法对 DCIS 的曲线下面积（AUC）为 0.89（95%置信区间为 0.77-1.00），对浸润性乳腺癌的 AUC 为 0.95（95%置信区间为 0.89-1.00）。这些 AUC 与乳房 X 光检查的观察结果相当。我们还发现，与没有发生癌症转移的患者相比，在原发性肿瘤后发生转移性疾病的乳腺癌患者的血清 HERV-K(HML-2)mRNA 水平往往更高。我们的研究结果表明，HERV-K(HML-2)抗体和 mRNA 在乳腺癌的早期阶段就已经在血液中升高，并且在有发生转移性疾病风险的患者中进一步升高。
