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MAML1和TWIST1共同过表达促进头颈部鳞状细胞癌的侵袭。

MAML1 and TWIST1 co-overexpression promote invasion of head and neck squamous cell carcinoma.

作者信息

Ardalan Khales Sima, Ebrahimi Ehsan, Jahanzad Eisa, Ardalan Khales Sahar, Forghanifard Mohammad Mahdi

机构信息

Department of Biology, Tehran North Branch, Islamic Azad University, Tehran, Iran.

Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran.

出版信息

Asia Pac J Clin Oncol. 2018 Oct;14(5):e434-e441. doi: 10.1111/ajco.12843. Epub 2018 Jan 15.

DOI:10.1111/ajco.12843
PMID:29333702
Abstract

AIMS

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide with considerable morbidity and mortality. Invasion and metastasis of HNSCC is a complex process involving multiple molecules and signaling pathways. Twist Family BHLH Transcription Factor 1 (TWIST1) and Mastermind-like 1 (MAML1) are essential in induction of epithelial-mesenchymal transition through direct regulation of implicated molecules in cellular adhesion, migration and invasion. Our aim in this study was to assess the clinical significance of MAML1 and TWIST1 expression in HNSCC, and elucidate the probable correlation between these genes to exhibit their possible associations with progression and metastasis of the disease.

METHODS

The gene expression profile of MAML1 and TWIST1 was assessed in fresh tumoral compared to distant tumor-free tissues of 55 HNSCC patients using quantitative real-time Polymerase chain reaction (PCR).

RESULTS

Significant overexpression of MAML1 and TWIST1 mRNA was observed in 49.1% and 38.2% (P ˂ 0.05) of tumor specimens, respectively. Overexpression of MAML1 was associated with vascular invasion (P = 0.048). Concomitant overexpression of MAML1 and TWIST1 was significantly correlated to each other (P = 0.004). Co-overexpression of the genes was significantly correlated to the various clinicopathological indices of poor prognosis including depth of tumor invasion (P < 0.01), lymphatic invasion and grade of tumor cell differentiation (P < 0.05).

CONCLUSIONS

Significant correlation between MAML1 and TWIST1 in HNSCC was revealed. This study was the first report elucidating MAML1 clinical relevance in HNSCC. These new findings suggest an oncogenic role for concomitant expression of MAML1 and TWIST1 genes in HNSCC invasion and metastasis.

摘要

目的

头颈部鳞状细胞癌(HNSCC)是全球第七大常见癌症,其发病率和死亡率相当高。HNSCC的侵袭和转移是一个复杂的过程,涉及多种分子和信号通路。Twist家族BHLH转录因子1(TWIST1)和主脑样蛋白1(MAML1)通过直接调控细胞黏附、迁移和侵袭相关分子,在诱导上皮-间质转化中起关键作用。本研究的目的是评估MAML1和TWIST1在HNSCC中的表达的临床意义,并阐明这些基因之间可能的相关性,以揭示它们与疾病进展和转移的可能关联。

方法

使用定量实时聚合酶链反应(PCR),在55例HNSCC患者的新鲜肿瘤组织与远处无肿瘤组织中评估MAML1和TWIST1的基因表达谱。

结果

分别在49.1%和38.2%的肿瘤标本中观察到MAML1和TWIST1 mRNA的显著过表达(P<0.05)。MAML1的过表达与血管侵袭相关(P = 0.048)。MAML1和TWIST1的同时过表达彼此显著相关(P = 0.004)。基因的共同过表达与包括肿瘤浸润深度(P<0.01)、淋巴侵袭和肿瘤细胞分化程度(P<0.05)在内的各种预后不良的临床病理指标显著相关。

结论

揭示了HNSCC中MAML1和TWIST1之间的显著相关性。本研究是阐明MAML1在HNSCC中的临床相关性的首篇报道。这些新发现表明,MAML1和TWIST1基因的同时表达在HNSCC侵袭和转移中具有致癌作用。

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