自分泌唾液酸化纤连蛋白耗竭的甲状腺癌由于 EMT 进展而预后不良。

Thyroid Cancer With Autocrine Sialyl-fibronectin Depletion Has a Poor Prognosis due to EMT Progression.

机构信息

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;

出版信息

Anticancer Res. 2024 Oct;44(10):4561-4568. doi: 10.21873/anticanres.17285.

DOI:10.21873/anticanres.17285

PMID:39348981

Abstract

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).

PATIENTS AND METHODS

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.

RESULTS

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.

CONCLUSION

S-FN-negative thyroid cancer has a poor prognosis because of the progression of EMT associated with increased paracrine FN levels in the stroma.

摘要

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。

患者和方法

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。

结果

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。