PCDH20 通过 Wnt/β-catenin 信号通路在下咽鳞癌中作为肿瘤抑制基因发挥作用。

PCDH20 acts as a tumour-suppressor gene through the Wnt/β-catenin signalling pathway in hypopharyngeal squamous cell carcinoma.

出版信息

Cancer Biomark. 2019;26(2):209-217. doi: 10.3233/CBM-190442.

DOI:10.3233/CBM-190442

Abstract

BACKGROUND

Downregulation of PCDH20 is frequently involved in tumorigenesis of many cancers, but the role of PCDH20 protein in hypopharyngeal squamous cell carcinoma (HSCC) is still unknown.

OBJECTIVE

The aim of this study was to investigate the role of PCDH20 in hypopharyngeal squamous cell carcinoma (HSCC).

METHODS

Immunohistochemistry (IHC) and qRT-PCR was carried out to estimate the expressions of PCDH20 protein and mRNA in HSCC tissues and adjacent non-tumor tissues. Correlation between the PCDH20 expression and clinicopathological characteristics was evaluated using chi-square test. Meanwhile, Kaplan-Meier method and log-rank test were applied to analyze the overall survival. After transfection of PCDH20, the CCK8 assay, Cell migration assay and invasion assay were used to investigate the changes in the viability, migration and invasion of Fuda cells. The mechanisms by which reduced PCDH20 promote migration and invasion of Fuda cells were examined using western blotting.

RESULTS

PCDH20 protein showed in tumor tissue low expression rates of 67.5% (54/80). The mRNA of PCDH20 indicated the consistent trend (80%, 8/10). Reduced PCDH20 expression was positively related to T stage and lymph node metastasis (P< 0.05). Patients with low levels of PCDH20 had worse overall survival compared with those with high PCDH20 levels (P< 0.001). The univariate Cox regression analysis described that lymph node metastasis (P= 0.043) and down-regulated PCDH20 expression (P= 0.045) were significantly prognostic factors.Multivariate analysis suggested that low PCDH20 expression (P= 0.015) were significantly independent prognostic factors for overall survival. PCDH20 in Fadu cells significantly inhibited cell viability, migration and invasion. Meanwhile, PCDH20 was involved in the disruption of HSCC progression through antagonizing its downstream Wnt/β-catenin signalling pathway.

CONCLUSION

Our data highlight that the downregulated PCDH20 may serve as reliable diagnostic biomarker in HSCC.

摘要

背景

PCDH20 的下调经常涉及许多癌症的肿瘤发生，但 PCDH20 蛋白在下咽鳞状细胞癌 (HSCC) 中的作用尚不清楚。

目的

本研究旨在探讨 PCDH20 在下咽鳞状细胞癌 (HSCC) 中的作用。

方法

采用免疫组织化学 (IHC) 和 qRT-PCR 法检测 HSCC 组织及相邻非肿瘤组织中 PCDH20 蛋白及 mRNA 的表达情况。采用卡方检验评估 PCDH20 表达与临床病理特征的相关性。同时，采用 Kaplan-Meier 法和 log-rank 检验分析总生存期。转染 PCDH20 后，采用 CCK8 检测、细胞迁移实验和侵袭实验检测 Fuda 细胞活力、迁移和侵袭的变化。采用 Western blot 检测下调 PCDH20 促进 Fuda 细胞迁移和侵袭的机制。

结果

PCDH20 蛋白在下咽癌组织中的低表达率为 67.5%（54/80）。PCDH20 mRNA 也表现出一致的趋势（80%，8/10）。下调的 PCDH20 表达与 T 分期和淋巴结转移呈正相关（P<0.05）。低 PCDH20 水平的患者总生存期明显低于高 PCDH20 水平的患者（P<0.001）。单因素 Cox 回归分析表明，淋巴结转移（P=0.043）和下调的 PCDH20 表达（P=0.045）是显著的预后因素。多因素分析提示，低 PCDH20 表达（P=0.015）是总生存期的显著独立预后因素。PCDH20 在 Fadu 细胞中显著抑制细胞活力、迁移和侵袭。同时，PCDH20 通过拮抗其下游 Wnt/β-catenin 信号通路参与破坏 HSCC 进展。