Department of Breast, Thyroid, Endocrine Surgery, Jikei University School of Medicine, Tokyo, Japan.
Department of Breast, Thyroid, Endocrine Surgery, Jikei University School of Medicine, Tokyo, Japan;
Anticancer Res. 2024 Oct;44(10):4561-4568. doi: 10.21873/anticanres.17285.
BACKGROUND/AIM: Elevated blood fibronectin (FN) levels have been observed in various cancers; however, their significance remains controversial. Herein, we measured the levels of sialyl-fibronectin (S-FN), a type of FN secreted by tumor cells, and investigated whether blood S-FN secretion is associated with recurrent metastasis and epithelial-mesenchymal transition (EMT).
An ELISA system recognizing S-FN was constructed, and the amount of S-FN in blood samples from 63 patients with thyroid carcinoma was measured. The relationship between S-FN secretion and clinical prognosis was also examined. Vimentin immunostaining was performed to identify the mesenchymal status of the cells during EMT.
After 12 years of observation, 17/63 patients had recurrent metastases, including nine cases of lymph node recurrence (LNR) and eight cases of remote metastasis (RM). LNR occurred in 7/39 (17.9%) of S-FN-negative cases, where 4/7 (57.1%) had two or more repeat recurrences. In S-FN-positive cases, LNR was observed in 2/24 cases (8.3%), and no repeat recurrence was observed. For RM, 6/39 (15.4%) patients were S-FN-negative, of which 5/6 (83.3%) had progressive disease even during treatment at metastasis. Of the S-FN-positive cases, RM was observed in 2/24 (8.3%) patients; progressive disease was observed in 1/2 (50.0%) patients. In 9/11 S-FN-negative recurrent metastasis cases (81.8%) and 2/4 S-FN-positive cases (50.0%), many vimentin-positive, FN-secreting cells were found in the interstitial tissue around the tumor.
S-FN-negative thyroid cancer has a poor prognosis because of the progression of EMT associated with increased paracrine FN levels in the stroma.
背景/目的：纤维连接蛋白（FN）在各种癌症中均有升高，但其意义仍存在争议。在此，我们测量了肿瘤细胞分泌的唾液酸化纤维连接蛋白（S-FN）的水平，并探讨了血液 S-FN 分泌是否与复发转移和上皮间质转化（EMT）有关。
构建了一种识别 S-FN 的 ELISA 系统，并测量了 63 例甲状腺癌患者血液样本中的 S-FN 含量。还检查了 S-FN 分泌与临床预后的关系。进行波形蛋白免疫染色以鉴定 EMT 期间细胞的间充质状态。
经过 12 年的观察，63 例患者中有 17 例发生了复发转移，包括 9 例淋巴结复发（LNR）和 8 例远处转移（RM）。S-FN 阴性病例中有 7/39（17.9%）发生 LNR，其中 4/7（57.1%）有两次或更多次复发。在 S-FN 阳性病例中，2/24（8.3%）发生 LNR，且无重复复发。对于 RM，39 例患者中有 6/39（15.4%）S-FN 阴性，其中 5/6（83.3%）即使在转移时的治疗中也有进行性疾病。在 S-FN 阳性病例中，2/24（8.3%）发生 RM，1/2（50.0%）患者有进行性疾病。在 9/11 例 S-FN 阴性复发转移病例（81.8%）和 2/4 例 S-FN 阳性病例（50.0%）中，在肿瘤周围间质中发现了许多波形蛋白阳性、FN 分泌细胞。
由于 EMT 进展导致基质中旁分泌 FN 水平增加，S-FN 阴性甲状腺癌的预后较差。
