Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Functional Proteo-Metabolomics, Institute of Biochemistry, University of Innsbruck, Innsbruck, Austria.
Clin Chem. 2022 Feb 1;68(2):344-353. doi: 10.1093/clinchem/hvab153.
Despite recent progress in liquid biopsy technologies, early blood-based detection of breast cancer is still a challenge.
We analyzed secretion of the protein cellular communication network factor 1 (CCN1, formerly cysteine-rich angiogenic inducer 61) in breast cancer cell lines by an enzyme-linked immunosorbent assay (ELISA). Soluble CCN1 in the plasma (2.5 µL) of 544 patients with breast cancer and 427 healthy controls was analyzed by ELISA. The breast cancer samples were acquired at the time of primary diagnosis prior to neoadjuvant therapy or surgery. A classifier was established on a training cohort of patients with breast cancer and age-adapted healthy controls and further validated on an independent cohort comprising breast cancer patients and healthy controls. Samples from patients with benign breast diseases were investigated as additional controls. Samples from patients with acute heart diseases (n = 127) were investigated as noncancer controls. The diagnostic accuracy was determined by receiver operating characteristic using the parameters area under the curve, sensitivity, and specificity.
CCN1 was frequently secreted by breast cancer cell lines into the extracellular space. Subsequent analysis of clinical blood samples from patients with breast cancer and age-adjusted healthy controls revealed an overall specificity of 99.0% and sensitivity of 80.0% for cancer detection. Remarkably, 81.5% of small T1 cancers were already CCN1-positive, while CCN1 concentrations in patients with benign breast lesions were below the threshold for breast cancer detection.
Circulating CCN1 is a potentially novel blood biomarker for the detection of breast cancer at the earliest invasive stage.
尽管液体活检技术最近取得了进展，但早期血液检测乳腺癌仍然是一个挑战。
我们通过酶联免疫吸附试验（ELISA）分析了乳腺癌细胞系中蛋白细胞通讯网络因子 1（CCN1，以前称为富含半胱氨酸的血管生成诱导因子 61）的分泌。通过 ELISA 分析了 544 例乳腺癌患者和 427 例健康对照者的血浆（2.5μL）中可溶性 CCN1。乳腺癌样本在新辅助治疗或手术前的原发性诊断时获得。在乳腺癌患者和年龄匹配的健康对照者的训练队列上建立了一个分类器，并在包括乳腺癌患者和健康对照者的独立队列上进行了进一步验证。良性乳腺疾病患者的样本作为附加对照进行了研究。急性心脏病患者（n=127）的样本作为非癌症对照进行了研究。通过使用曲线下面积、灵敏度和特异性等参数的接收者操作特征来确定诊断准确性。
CCN1 经常由乳腺癌细胞系分泌到细胞外空间。随后对乳腺癌患者和年龄匹配的健康对照者的临床血液样本进行分析，发现癌症检测的总体特异性为 99.0%，灵敏度为 80.0%。值得注意的是，81.5%的小 T1 癌已经呈 CCN1 阳性，而良性乳腺病变患者的 CCN1 浓度低于乳腺癌检测的阈值。
循环 CCN1 是一种潜在的新型血液生物标志物，可用于检测最早的侵袭性乳腺癌阶段。
