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Ral鸟苷酸解离抑制蛋白(RalGAPs)的低表达与头颈部鳞状细胞癌较差的总生存率相关。

Low expression of RalGAPs associates with the poorer overall survival of head and neck squamous cell carcinoma.

作者信息

Liu Shan, Shi Congyu, Wang Xiaoyi, Ma Xiangrui, Gao Pan

机构信息

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, China.

出版信息

Transl Cancer Res. 2021 Dec;10(12):5085-5094. doi: 10.21037/tcr-21-1489.

Abstract

BACKGROUND

The role of Ral and RalGAPs on the progression of head and neck squamous cell carcinoma (HNSC) remains unclear.

METHODS

The predesigned siRNAs against RalGAPs were transfected into cells to evaluate the effect on RalA activation. The Data from TCGA and GTEx were combined to analyze the pan-cancer gene expression of RalA and RalGAPs in cancer and adjacent normal tissues. Kaplan-Meier analysis was used to assess the predictive value of RalA and RalGAPs expression on the overall survival of patients with HNSC. Methylation-specific PCR and next-generation bisulfite sequencing were used to evaluate the association between DNA methylation and the down-regulation of RalGAPs.

RESULTS

RalGAPs negatively regulated RalA activation. HNSC patients with low level of had worse overall survival. The promoter of was widely methylated in comparison to and the DNA methylation level of promoter was increased in HNSC tissues and associated with the presence of neck lymph node metastasis.

CONCLUSIONS

RalA and RalGAPs could act as a specific predictor to assess the prognosis of HNSC. DNA methylation might be a potential mechanism that downregulated the expression.

摘要

背景

Ral和RalGAPs在头颈部鳞状细胞癌(HNSC)进展中的作用仍不清楚。

方法

将针对RalGAPs的预先设计的小干扰RNA转染到细胞中,以评估对RalA激活的影响。合并来自TCGA和GTEx的数据,分析RalA和RalGAPs在癌症及相邻正常组织中的泛癌基因表达。采用Kaplan-Meier分析评估RalA和RalGAPs表达对HNSC患者总生存的预测价值。使用甲基化特异性PCR和下一代亚硫酸氢盐测序评估DNA甲基化与RalGAPs下调之间的关联。

结果

RalGAPs负向调节RalA激活。RalGAPs水平低的HNSC患者总生存较差。与正常组织相比,RalGAPs的启动子广泛甲基化,且RalGAPs启动子的DNA甲基化水平在HNSC组织中升高,并与颈部淋巴结转移的存在相关。

结论

RalA和RalGAPs可作为评估HNSC预后的特异性预测指标。DNA甲基化可能是RalGAPs表达下调的潜在机制。

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