Department of Surgery, MacKay Memorial Hospital, Mackay Medical College, 92, Chung-Shan North Road, Section 2, Taipei, 10449, Taiwan.
Department of Pharmacology, Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
Clin Exp Med. 2017 Nov;17(4):555-564. doi: 10.1007/s10238-016-0445-y. Epub 2016 Dec 21.
Although papillary thyroid cancer is a relatively indolent malignancy, its progression may be associated with dedifferentiation and resistance to radioactive iodine treatment. In this study, patterns of differentially expressed genes in association with disease progression were systemically evaluated. We firstly performed transcriptome analyses for four matched cancerous and noncancerous tissue pairs of the classical subtype of papillary thyroid cancer. Among the upregulated and downregulated genes, the expression of 164 and 183 genes increased and decreased, respectively, from stage I to stage IV. Functional enrichment and pathway analysis showed that angiogenesis pathway was upregulated, whereas oxidation-reduction and metabolism of reactive oxygen species were downregulated. Teneurin transmembrane protein 1 (TENM1) expression was highly upregulated in cancerous tissues and negative in benign thyroid tissues. By immunohistochemistry, TENM1 expression in papillary thyroid cancer was associated with the classical subtype (p = 0.018), extrathyroidal invasion (p = 0.001), BRAF V600E mutation (p < 0.001), and an advanced stage (p = 0.019). Taken together, our results indicate that distinct pathways are involved in papillary thyroid cancer progression, and TENM1 is a potential marker of cancer progression.
尽管甲状腺乳头状癌是一种相对惰性的恶性肿瘤，但它的进展可能与去分化和对放射性碘治疗的耐药性有关。在这项研究中，我们系统地评估了与疾病进展相关的差异表达基因模式。我们首先对 4 对经典型甲状腺乳头状癌的配对癌组织和非癌组织进行了转录组分析。在上调和下调的基因中，从 I 期到 IV 期，分别有 164 个和 183 个基因的表达增加和减少。功能富集和通路分析表明，血管生成途径被上调，而氧化还原和活性氧代谢被下调。神经粘蛋白跨膜蛋白 1（TENM1）在癌组织中高表达，在良性甲状腺组织中为阴性。通过免疫组织化学，甲状腺乳头状癌中 TENM1 的表达与经典型（p=0.018）、甲状腺外侵犯（p=0.001）、BRAF V600E 突变（p<0.001）和晚期（p=0.019）相关。总之，我们的研究结果表明，不同的通路参与了甲状腺乳头状癌的进展，TENM1 是癌症进展的潜在标志物。
