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甲状腺肿瘤中与自分泌运动因子-溶血磷脂酸信号相关的蛋白表达。

Expression of proteins related to autotaxin-lysophosphatidate signaling in thyroid tumors.

机构信息

Department of Pathology, CHA Gangnam Medical Center, CHA University School of Medicine, Seoul, South Korea.

Department of Pathology, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.

出版信息

J Transl Med. 2019 Aug 28;17(1):288. doi: 10.1186/s12967-019-2028-7.

Abstract

BACKGROUND

We aimed to investigate the expression of proteins related with autotaxin (ATX)-lysophosphatidate (LPA) signaling and the clinical implications in primary and metastatic thyroid tumors.

METHODS

We constructed tissue microarrays with 545 primary thyroid tumors [338 papillary thyroid carcinoma (PTC), 111 follicular carcinoma (FC), 69 medullary carcinoma (MC), 23 poorly differentiated carcinoma (PDC), and four anaplastic carcinoma (AC)]. Immunohistochemical stains for proteins related to ATX-LPA signaling (e.g., ATX, LPA1, LPA2, and LPA3) were performed.

RESULTS

The expression of ATX was highest in MC, while the LPA1 expression was higher in PDC and AC, and the expression of LPA2 and LPA3 was highest in PTC (p < 0.001). Additionally, the expression of ATX, LPA1, and LPA2 was higher in conventional-type PTC than in follicular-variant PTC (p < 0.05). PTC with BRAF V600E mutation showed higher expression of ATX, LPA1, LPA2, and LPA3 than PTC without BRAF V600E mutation (p < 0.001). In univariate analysis, ATX positivity (p = 0.005) and LPA1 positivity (p = 0.014) were correlated with shorter overall survival in PTC.

CONCLUSION

Proteins related to the ATX-LPA axis showed different levels of expression in primary thyroid tumors according to subtype.

摘要

背景

我们旨在研究与自分泌酶(ATX)-溶血磷脂酸(LPA)信号相关的蛋白表达及其在原发性和转移性甲状腺肿瘤中的临床意义。

方法

我们构建了包含 545 例原发性甲状腺肿瘤[338 例甲状腺乳头状癌(PTC)、111 例滤泡状癌(FC)、69 例髓样癌(MC)、23 例低分化癌(PDC)和 4 例间变性癌(AC)]的组织微阵列,并进行了与 ATX-LPA 信号相关的蛋白(如 ATX、LPA1、LPA2 和 LPA3)的免疫组织化学染色。

结果

ATX 在 MC 中的表达最高,而 LPA1 在 PDC 和 AC 中的表达更高,LPA2 和 LPA3 在 PTC 中的表达最高(p<0.001)。此外,与滤泡型 PTC 相比,经典型 PTC 中 ATX、LPA1 和 LPA2 的表达更高(p<0.05)。具有 BRAF V600E 突变的 PTC 与不具有 BRAF V600E 突变的 PTC 相比,ATX、LPA1、LPA2 和 LPA3 的表达更高(p<0.001)。在单因素分析中,ATX 阳性(p=0.005)和 LPA1 阳性(p=0.014)与 PTC 患者的总生存时间较短相关。

结论

根据亚型的不同,与 ATX-LPA 轴相关的蛋白在原发性甲状腺肿瘤中表达水平不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1588/6712878/c24e498bd090/12967_2019_2028_Fig1_HTML.jpg

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