Yoshikawa Mio, Iinuma Hisae, Umemoto Yasuko, Yanagisawa Takako, Matsumoto Akiko, Jinno Hiromitsu
Department of Surgery, Teikyo University School of Medicine, Tokyo 173-0003, Japan.
Oncol Lett. 2018 Jun;15(6):9584-9592. doi: 10.3892/ol.2018.8457. Epub 2018 Apr 10.
Patients diagnosed preoperatively with ductal carcinoma (DCIS) breast cancer have the potential to develop invasive ductal carcinoma (IDC). The present study investigated the usefulness of exosome-encapsulated microRNA-223-3p (miR-223-3p) as a biomarker for detecting IDC in patients initially diagnosed with DCIS by biopsy. The potential association between miR-223-3p and clinicopathological characteristics was examined in patients with breast cancer. Exosomes of 185 patients with breast cancer were separated from plasma by ultracentrifugation. Initially a microRNA (miRNA) microarray was examined to reveal the invasion specific miRNAs using exosomes collected from 6 patients with breast cancer, including 3 DCIS patients, 3 IDC patients and 3 healthy controls. In the miR microarray analysis the miR-223-3p levels of IDC patients demonstrated the highest fold-change compared with those in the DCIS patients and healthy controls. The potential of miR-223-3p for cell proliferation and cell invasion were examined using MCF7 cells transfected with the miR-223-3p gene. MCF7 cells transfected with the miR-223-3p gene significantly promoted cell proliferation and cell invasive ability (P<0.05). The plasma exosomal miR-223-3p levels of the other 179 patients with breast cancer and 20 healthy controls were measured using TaqMan miR assays. The exosomal miR-223-3p levels of the patients with breast cancer were significantly increased compared with the healthy controls (P<0.01). A statistically significant association was observed between the exosomal miR-223-3p levels and histological type, pT stage, pN stage, pathological stage, lymphatic invasion and nuclear grade (P<0.05). The exosomal miR-223-3p levels of IDC patients (stage I) and upstaged IDC patients (stage I) were significantly higher compared with the DCIS patients (P<0.05). These results suggest that exosomal miR-223-3p may be a useful preoperative biomarker to identify the invasive lesions of DCIS patients diagnosed by biopsy. In addition, plasma exosome-encapsulated miR-223-3p level was significantly associated with the malignancy of breast cancer.
术前被诊断为乳腺导管原位癌（DCIS）的患者有可能发展为浸润性导管癌（IDC）。本研究调查了外泌体包裹的微小RNA-223-3p（miR-223-3p）作为活检初诊为DCIS患者中检测IDC生物标志物的有效性。在乳腺癌患者中检测了miR-223-3p与临床病理特征之间的潜在关联。通过超速离心从185例乳腺癌患者的血浆中分离出外泌体。最初，使用从6例乳腺癌患者（包括3例DCIS患者、3例IDC患者和3例健康对照）收集的外泌体进行微小RNA（miRNA）微阵列检测，以揭示侵袭特异性miRNA。在miR微阵列分析中，IDC患者的miR-223-3p水平与DCIS患者和健康对照相比显示出最高的倍数变化。使用转染了miR-223-3p基因的MCF7细胞检测miR-223-3p对细胞增殖和细胞侵袭的影响。转染了miR-223-3p基因的MCF7细胞显著促进细胞增殖和细胞侵袭能力（P<0.05）。使用TaqMan miR检测法测量另外179例乳腺癌患者和20例健康对照的血浆外泌体miR-223-3p水平。乳腺癌患者的外泌体miR-223-3p水平与健康对照相比显著升高（P<0.01）。在外泌体miR-223-3p水平与组织学类型、pT分期、pN分期、病理分期、淋巴侵袭和核分级之间观察到统计学上的显著关联（P<0.05）。IDC患者（I期）和分期上调的IDC患者（I期）的外泌体miR-223-3p水平与DCIS患者相比显著更高（P<0.05）。这些结果表明，外泌体miR-223-3p可能是一种有用的术前生物标志物，用于识别活检诊断的DCIS患者的浸润性病变。此外，血浆外泌体包裹的miR-223-3p水平与乳腺癌的恶性程度显著相关。
