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

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

doi:10.21037/tcr-21-1489

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

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

Authors

Shan Liu¹, Congyu Shi¹, Xiaoyi Wang¹, Xiangrui Ma², Pan Gao³

Affiliations

¹ 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.
² Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, China.
³ State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of General and Emergency Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

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 in vitro and next-generation bisulfite sequencing in vivo 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 RalGAPα2 had worse overall survival. The promoter of RalGAPα2 was widely methylated in comparison to RalGAPα1 and the DNA methylation level of RalGAPα2 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 RalGAPα2 expression.

Keywords: DNA methylation; GTPase-activating proteins; Head and neck squamous cell carcinoma (HNSC); Ral protein.