Department of Thoracic Surgery, Medical Faculty, School of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey.
Department of Thoracic Surgery, Private Antalya Med-Star Hospital, Antalya, Turkey.
Mol Biol Rep. 2022 Jan;49(1):9-17. doi: 10.1007/s11033-021-06759-2. Epub 2021 Nov 15.
We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors.
The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis.
The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039).
In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.
我们旨在检测在 Wnt 信号通路中发挥作用的腺瘤性结肠息肉病基因 1（APC1）、APC-2、Dickkopf 相关蛋白 1（DKK1）、DKK3、分泌型卷曲相关蛋白 2（SFRP2）、SFRP4 和 SFRP5 的基因在肺腺癌及癌旁正常肺组织中的表达水平，并评估其与临床病理因素的关系。
采用实时 PCR 分析，检测 2011 年至 2018 年间 57 例行肺腺癌手术患者的肿瘤组织和癌旁完整肺组织中基因的表达水平。
肿瘤组织中 DKK-1 的表达水平，特别是在 I-II 期肿瘤组织中，明显低于正常组织（p<0.025）。虽然早期肺腺癌患者肿瘤组织中 DKK-1 的表达受到抑制，但这些患者的肿瘤组织中 SFRP-5 的表达明显高于正常组织（p<0.039）。
在本研究中，我们发现已知是 Wnt 信号通路细胞外拮抗剂的 SFRP-5 和 DKK-1 之间存在相反的调节作用。SFRP-5 在腺癌发展中具有致癌作用。对早期肺腺癌中这些基因之间的相反调节作用的研究可能揭示与癌变发展相关的机制。这些基因的关系或相互作用可能作为潜在的治疗靶点。
