KRT84 是口腔鳞状细胞癌的潜在肿瘤抑制因子和良好预后标志物。

KRT84 is a potential tumor suppressor and good prognosis signature of oral squamous cell carcinoma.

机构信息

Department of Stomatology, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin 300192, P.R. China.

出版信息

Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20200187.

DOI:10.1042/BSR20200187

PMID:32181476

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7109001/

Abstract

AIMS

Oral squamous cell carcinoma (OSCC) is a common oral cancer; however, current therapeutic approaches still show limited efficacy. Our research aims to explore effective biomarkers related to OSCC.

MAIN METHODS

Gene expression profiles of paired OSCC tumor and paracancerous samples from The Cancer Genome Atlas (TCGA) were analyzed. mRNA and protein levels of KRT84 in OSCC cell line HSC-3 were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. KRT84 protein levels in OSCC tumor samples of different stages were determined by immunohistochemistry. Overall survival (OS) of OSCC samples was evaluated and association of multiple factors with OS was assessed.

KEY FINDINGS

Compared with paracancerous samples, 4642 DEGs were identified in OSCC tumor samples. Among them, KRT84 expression level in OSCC tumor tissues was obviously decreased, which was validated in HSC-3 cells. KRT84 expression level showed decreasing tendency with the increase of tumor grade and stage. Patients with low KRT84 expression level had inferior OS independently of multiple factors. Besides, antigen processing and presentation pathway were significantly activated in OSCC samples with high KRT84 expression. Elevated KRT84 mRNA as well as protein levels were confirmed by RT-qPCR and Western blot in OSCC and normal cell lines, and immunohistochemistry in OSCC tumor and paracancerous tissues.

SIGNIFICANCE

Our study suggests KRT84 as a tumor suppressor and good prognostic indicator for OSCC, which might be significant for OSCC diagnosis and treatment.

摘要

目的

口腔鳞状细胞癌（OSCC）是一种常见的口腔癌，但目前的治疗方法仍显示出有限的疗效。我们的研究旨在探索与 OSCC 相关的有效生物标志物。

方法

分析了来自癌症基因组图谱（TCGA）的配对 OSCC 肿瘤和癌旁样本的基因表达谱。通过实时定量聚合酶链反应（RT-qPCR）和 Western blot 测量 OSCC 细胞系 HSC-3 中 KRT84 的 mRNA 和蛋白水平。通过免疫组织化学测定不同阶段 OSCC 肿瘤样本中的 KRT84 蛋白水平。评估 OSCC 样本的总生存期（OS），并评估多个因素与 OS 的相关性。

主要发现

与癌旁样本相比，在 OSCC 肿瘤样本中鉴定出 4642 个差异表达基因。其中，KRT84 在 OSCC 肿瘤组织中的表达水平明显降低，在 HSC-3 细胞中得到验证。KRT84 表达水平随着肿瘤分级和分期的增加而呈下降趋势。无论多个因素如何，KRT84 低表达的患者 OS 较差。此外，抗原加工和呈递途径在 KRT84 高表达的 OSCC 样本中明显激活。通过 RT-qPCR 和 Western blot 在 OSCC 和正常细胞系中以及在 OSCC 肿瘤和癌旁组织中的免疫组织化学证实了升高的 KRT84 mRNA 和蛋白水平。