Takeyama Hiroshi, Manome Yoshinobu
Department of Breast, Thyroid, Endocrine Surgery, Jikei University School of Medicine, Tokyo, Japan.
Department of Molecular Cell Biology, Jikei University School of Medicine, Tokyo, Japan.
Cancer Diagn Progn. 2023 Sep 3;3(5):558-570. doi: 10.21873/cdp.10255. eCollection 2023 Sep-Oct.
BACKGROUND/AIM: Elevated blood fibronectin (FN) levels have been observed in various cancers; however, their significance is controversial. We measured sialyl-fibronectin (S-FN), a type of FN secreted by tumor cells in the blood, and investigated whether blood S-FN secretion is associated with cancer malignancy and recurrent metastases.
We constructed an enzyme-linked immunosorbent assay (ELISA) system that recognizes S-FN as an antigen and measured the amount of S-FN secreted into the blood of 89 patients with breast tumors. The relationship between S-FN secretion and prognostic predictors was analyzed. Immunostaining was performed to identify the site of S-FN secretion in the breast tissue.
Among the 82 patients, 21 (25.6%, 21/82) and 61 (74.4%, 61/82) were blood S-FN-positive and S-FN-negative, respectively. Regarding prognostic predictors, blood S-FN-positive and S-FN-negative patients showed significant difference in locoregional recurrence (p=0.026), remote metastases (p=0.049), and histological margins (p=0.001). Locoregional recurrence was associated with positive histological margins in S-FN-positive patients. However, remote metastases were associated with N-factor and histological classification (HC) in S-FN-negative patients. Furthermore, S-FN particles were detected in the cytoplasm of breast cancer cells through immunostaining. After the onset of recurrent metastases, two S-FN-positive and six S-FN-negative patients received anticancer drug treatment; however, further progression was observed in five S-FN-negative patients.
S-FN-positive patients are less likely to develop distant metastases, have a better prognosis, and may be less resistant to therapeutic agents than S-FN-negative patients, which contain many epithelial-mesenchymal transition cells.
背景/目的:在多种癌症中均观察到血液中纤连蛋白(FN)水平升高;然而,其意义存在争议。我们检测了唾液酸化纤连蛋白(S-FN),一种肿瘤细胞分泌到血液中的FN类型,并研究血液中S-FN的分泌是否与癌症恶性程度及复发转移相关。
我们构建了一种以S-FN为抗原的酶联免疫吸附测定(ELISA)系统,并检测了89例乳腺肿瘤患者血液中分泌的S-FN量。分析了S-FN分泌与预后预测指标之间的关系。进行免疫染色以确定乳腺组织中S-FN的分泌部位。
在82例患者中,血液S-FN阳性和阴性的分别有21例(25.6%,21/82)和61例(74.4%,61/82)。关于预后预测指标,血液S-FN阳性和阴性患者在局部区域复发(p=0.026)、远处转移(p=0.049)和组织学切缘(p=0.001)方面存在显著差异。S-FN阳性患者的局部区域复发与组织学切缘阳性相关。然而,S-FN阴性患者的远处转移与N因子和组织学分类(HC)相关。此外,通过免疫染色在乳腺癌细胞的细胞质中检测到S-FN颗粒。在复发转移发生后,2例S-FN阳性和6例S-FN阴性患者接受了抗癌药物治疗;然而,5例S-FN阴性患者出现了进一步进展。
与含有许多上皮-间质转化细胞的S-FN阴性患者相比,S-FN阳性患者发生远处转移的可能性较小,预后较好,且可能对治疗药物的耐药性较低。