Shibata Masahiro, Inaishi Takahiro, Ichikawa Takahiro, Shimizu Dai, Soeda Ikumi, Takano Yuko, Takeuchi Dai, Tsunoda Nobuyuki, Kikumori Toyone
Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
Surg Today. 2021 Oct;51(10):1703-1712. doi: 10.1007/s00595-021-02262-0. Epub 2021 Mar 17.
Papillary thyroid cancer (PTC) is generally associated with a favorable prognosis. However, some patients have fatal disease, with locally infiltrating tumors or progressive distant metastases; yet few studies have investigated the characteristics of the tumor-progressive gene expression profile in advanced PTC. We conducted this study to clarify the gene expression status in advanced PTC and identify candidate molecules for prognostic biomarkers.
We analyzed 740 tumor-progressive gene expression levels from formalin-fixed paraffin-embedded blocks of samples from six patients with low-risk PTC and six patients with high-risk PTC, using the nCounter PanCancer Progression panel. Then, we investigated the association between the expression levels of focused genes and pathological factors in PTC patients in The Cancer Genome Atlas (TCGA) database.
The expression levels of 14 genes in the high-risk PTC specimens were more than two-fold those in the low-risk PTC specimens. In the TCGA database, expression levels of four genes (CCL11, COL6A3, INHBA, and SRPX2) were significantly higher in patients with advanced PTC. Among the patients with advanced PTC, those with high SRPX2 expression levels had poor disease-free survival. Univariate and multivariate analyses revealed that high SRPX2 expression was an independent prognostic factor.
Based on the findings of this study, CCL11, COL6A3, INHBA, and SRPX2 are potential biomarkers that indicate advanced PTC. SRPX2, in particular, is considered a prognostic biomarker.
甲状腺乳头状癌（PTC）通常预后良好。然而，一些患者患有致命性疾病，伴有局部浸润性肿瘤或进行性远处转移；但很少有研究调查晚期PTC中肿瘤进展基因表达谱的特征。我们开展这项研究以阐明晚期PTC中的基因表达状态，并确定预后生物标志物的候选分子。
我们使用nCounter泛癌进展检测板分析了来自6例低风险PTC患者和6例高风险PTC患者的福尔马林固定石蜡包埋样本中的740个肿瘤进展基因表达水平。然后，我们在癌症基因组图谱（TCGA）数据库中研究了PTC患者中重点基因的表达水平与病理因素之间的关联。
高风险PTC标本中14个基因的表达水平是低风险PTC标本中的两倍以上。在TCGA数据库中，晚期PTC患者中4个基因（CCL11、COL6A3、INHBA和SRPX2）的表达水平显著更高。在晚期PTC患者中，SRPX2表达水平高的患者无病生存期较差。单因素和多因素分析显示，高SRPX2表达是一个独立的预后因素。
基于本研究结果，CCL11、COL6A3、INHBA和SRPX2是指示晚期PTC的潜在生物标志物。特别是SRPX2，被认为是一种预后生物标志物。
