Identification of an Anoikis-Related Gene Signature to Predict the Prognosis in Patients With Oral Squamous Cell Carcinoma

Anoikis plays an important role in cancer metastasis. Nevertheless, research that focuses on the prognostic values of anoikis-related genes (ARGs) in oral squamous cell carcinoma (OSCC) is still scarce. The ARG-related gene signature was developed via LASSO regression using the TCGA-OSCC cohort. OSCC patients in the TCGA_OSCC and GSE41613 datasets were grouped into high- and low-ARG score (H-score, L-score) groups, and the overall survival (OS) between the 2 groups was analysed. Meanwhile, functional enrichment, CIBERSORT and drug sensitivity were conducted based on the data from the TCGA_OSCC cohort. Loss-of-function assay was employed to explore the biological roles of SPINK1 in OSCC. In the current research, we constructed a novel prognostic model based on 5 ARGs (SPINK1, PLAU, VEGFA, PLK1 and EGF) for OSCC. The OS of OSCC patients in the H-score group was worse than that in the L-score group. Moreover, patients with the H-score had low immune and ESTIMATE scores, suggesting a declined immune status in these patients. Additionally, some tumour-promoting signalling pathways (e.g. focal adhesion, PI3K-Akt and WNT signalling pathways) were notably activated in the H-score group. Functionally, downregulation of SPINK1 notably suppressed OSCC cell viability, migration and invasion and induced ferroptosis through inactivation of the Nrf2/GPX4 signalling pathway. We have developed a novel 5-gene signature related to ARG, which may serve as a predictor for OS in patients with OSCC. Our findings may open a new possibility of providing personalised treatment for OSCC patients.