Expression profile and function of secretogranin V, and its effects on the malignant behavior of esophageal squamous cell carcinoma.

IF 2.6 3区 医学
Mohammad Hussain Hamrah, Mitsuro Kanda, Yusuke Sato, Haote Zhu, Tuvshin Bayasgalan, Flor Garza, Takahiro Shinozuka, Yuki Ito, Masahiro Sasahara, Dai Shimizu, Shinichi Umeda, Hideki Takami, Norifumi Hattori, Masamichi Hayashi, Chie Tanaka, Yasuhiro Kodera
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Abstract

Esophageal squamous cell carcinoma (ESCC) is recognized as one of the most aggressive cancers with a poor prognosis. Global expression profiling was conducted on primary ESCC tissues with distant metastases. We investigated the identification of secretogranin V (SCG5) as a promising biomarker for the detection and assessment of ESCC. SCG5 transcription levels were evaluated in 21 ESCC cell lines. Small interfering RNA-mediated knockdown experiments validated SCG5's roles in cell invasion, proliferation, and migration. We utilized a mouse subcutaneous xenograft model to assess tumor growth. SCG5 expression was measured in 164 ESCC tissues by quantitative reverse transcription quantitative polymerase chain reaction, and its association with clinicopathological parameters was investigated. SCG5 protein levels were assessed in surgically resected tissues from 177 patients with ESCC using a tissue microarray. The mRNA expression levels of SCG5 varied widely in ESCC cell lines. The in vitro cell invasion, proliferation, and migration of ESCC cells were suppressed by the knockdown of SCG5. Mouse xenograft models revealed that tumor growth was reduced by small interfering RNA-mediated SCG5 knockdown. Analysis of clinical samples demonstrated that SCG5 mRNA was expressed in ESCC compared to adjacent normal esophageal tissues. High SCG5 mRNA expression was linked to significant decreases in overall and disease-specific survival. Furthermore, SCG5 protein expression was linked to a decrease in disease-specific survival and disease-free survival. The expression of the SCG5 was significantly associated with disease-specific survival, suggesting that SCG5 may play a significant role as a diagnostic and prognostic biomarker for ESCC.

分泌格拉宁 V 的表达谱和功能及其对食管鳞状细胞癌恶性行为的影响
食管鳞状细胞癌(ESCC)是公认的侵袭性最强、预后最差的癌症之一。我们对伴有远处转移的原发性 ESCC 组织进行了全局表达谱分析。我们研究了如何将分泌格拉宁 V (SCG5) 鉴定为检测和评估 ESCC 的一种有前景的生物标记物。我们评估了 21 种 ESCC 细胞系的 SCG5 转录水平。小干扰 RNA 介导的基因敲除实验验证了 SCG5 在细胞侵袭、增殖和迁移中的作用。我们利用小鼠皮下异种移植模型来评估肿瘤生长情况。通过反转录定量聚合酶链反应测定了 164 例 ESCC 组织中 SCG5 的表达,并研究了其与临床病理参数的关系。使用组织芯片评估了177例ESCC患者手术切除组织中的SCG5蛋白水平。在 ESCC 细胞系中,SCG5 的 mRNA 表达水平差异很大。敲除 SCG5 能抑制 ESCC 细胞的体外侵袭、增殖和迁移。小鼠异种移植模型显示,小干扰 RNA 介导的 SCG5 基因敲除可减少肿瘤生长。对临床样本的分析表明,与邻近的正常食管组织相比,SCG5 mRNA在ESCC中表达。SCG5 mRNA的高表达与总存活率和疾病特异性存活率的显著下降有关。此外,SCG5 蛋白表达与疾病特异性生存率和无病生存率的下降有关。SCG5的表达与疾病特异性生存显著相关,这表明SCG5作为ESCC的诊断和预后生物标志物可能会发挥重要作用。
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来源期刊
Diseases of the Esophagus
Diseases of the Esophagus Medicine-Gastroenterology
自引率
7.70%
发文量
568
期刊介绍: Diseases of the Esophagus covers all aspects of the esophagus - etiology, investigation and diagnosis, and both medical and surgical treatment.
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