Background: Oral squamous cell carcinoma (OSCC) is the most common subtype of head and neck squamous cell carcinoma (HNSC) and poses a serious threat to human health. The molecular mechanisms underlying the initiation and progression of OSCC are highly complex. Although notable advances have been made in diagnostic and therapeutic technologies in recent years, the five-year survival rate of patients has not improved substantially. Therefore, in-depth investigation of the molecular mechanisms of OSCC, identification of potential diagnostic and therapeutic biomarkers, and development of effective treatment strategies have become critical directions in current research. Aim: To investigate the relationship between the prognosis of HNSC/OSCC and the m7G-related lncRNA GSEC. Materials and Methods: RNA-seq transcriptome data and clinical data for HNSC were downloaded from The Cancer Genome Atlas (TCGA). Differential expression analysis of lncRNAs was performed, and differentially expressed lncRNAs were selected. Univariate Cox regression analysis was used to screen lncRNAs associated with prognosis. The random forest algorithm was employed to rank the importance of differentially expressed lncRNAs, and the top 50 lncRNAs were selected. Twenty-nine m7G-related genes were obtained from published literature. m7G-related lncRNAs were screened based on Pearson correlation analysis. The intersection of these results was taken to identify diagnostic biomarker m7G-related lncRNAs. The UALCAN database was used to analyze the expression of target m7G-related lncRNA in HNSC/OSCC. cBioPortal was used to analyze the gene mutation profile of GSEC in HNSC. Co-expressed genes of the target lncRNA in HNSC were collected via cBioPortal, filtering for genes with FDR<0.05 and R>0.4. GO/KEGG enrichment analysis was performed using the Metascape database. Immunohistochemical expression levels of the m7G-related gene were analyzed using the Human Protein Atlas (HPA) database. The expression level of the m7G-related lncRNA in cells was detected using qRT-PCR. Result: A total of 3,618 differentially expressed lncRNAs were identified in HNSC from the TCGA database, including 2,421 upregulated and 1,197 downregulated genes. Univariate Cox regression analysis showed that 1,306 lncRNAs were significantly associated with HNSC patient prognosis (P<0.05). The random forest algorithm ranked the top 50 important lncRNAs. Pearson correlation analysis (|correlation coefficient|>0.5, P<0.001) identified 310 m7G-related lncRNAs. Taking the intersection with lncRNAs significant in the random forest and univariate Cox regression analyses revealed that the m7G-related lncRNA GSEC has significant diagnostic value in HNSC, with DCPS identified as the m7G-related gene for lncRNA GSEC. GSEC/DCPS were significantly upregulated in HNSC/OSCC (P<0.05). High expression of GSEC showed value in predicting poor outcomes in OSCC (AUC=0.937). Analysis of the mutation spectrum of the target gene GSEC indicated that GSEC undergoes genetic mutations in HNSC, including amplification and altered mRNA expression levels. Enrichment analysis of GSEC co-expressed genes in HNSC (FDR<0.05, R>0.4) revealed that GO terms were primarily enriched in the endoplasmic reticulum lumen, glycoprotein metabolic process, and collagen fibril organization. KEGG pathways were mainly enriched in Protein processing in endoplasmic reticulum, Glycosaminoglycan biosynthesis-heparan sulfate/heparin, and Lysine degradation. Immunohistochemical analysis revealed high expression of DCPS, the m7G-related protein within the GSEC, in OSCC tissues compared to normal mucosal tissues. Further qRT-PCR detection demonstrated that GSEC is upregulated in OSCC cell lines relative to NHOK cells. Among the OSCC cell lines examined, CAL-27 exhibited the most pronounced upregulation of GSEC expression compared to SCC-4 and HSC-2 cells. Conclusion Bioinformatics analysis in this study revealed significant upregulation of the m7G-related GSEC/DCPS in HNSC/OSCC. Moreover, GSEC/DCPS expression was correlated with the prognosis of HNSC/OSCC. These findings suggest that GSEC/DCPS may serve as a novel molecular target for the diagnosis and treatment of HNSC/OSCC.

Background: According to the World Health Organization (WHO), oral cancer is one of the most common malignancies of the head and neck region, ranking 16th among all cancers worldwide. Approximately 90% of oral cancers are oral squamous cell carcinomas. The development of this malignancy is influenced by multiple factors, and some genes plays a crucial role in development of the cancer. In recent years, the potential association between lncRNA GSEC and cancer has attracted significant research interest. Aim: This study aimed to investigate some functions of lncRNA GSEC in oral squamous cell carcinoma (OSCC) in vivo experimental model. Materials and Methods: To examine the role of GSEC in the proliferation of human oral cancer cells (CAL27), fifteen healthy 5-week-old BALB/c nude mice were divided into three groups: group Blank (CAL27 cells alone), NC (control si-NC CAL27 cells), and si-GSEC (si-GSEC CAL27 cells). The mice were subcutaneously injected with CAL27 cells alone, control si-NC CAL27 cells and si-GSEC CAL27 cells. Body weight and tumor size of the mice were measured throughout the experiment. On day 13, the mice were sacrificed, tumor tissues were excised and weighed, and the tumor tissues were stained using hematoxylin–eosin (HE) and immunohistochemistry to examine the expression of proliferation-related proteins Ki-67 and PCNA. Results: No significant differences in body weight were observed among the three groups of the mice up to day 13. However, the excised tumors from the si-GSEC CAL27 group were significantly smaller and lighter than those from the si- NC CAL27 and CAL27-only groups (p < 0.001). HE staining showed that tumor tissues in the si-GSEC group had more organized structure, better cellular differentiation, fewer malignant cells, decreased nuclear division, and reduced tumor transformation compared with the other groups. Immunohistochemical analysis revealed that Ki-67 and PCNA expression in tumor tissues was heterogeneously distributed, with higher density in peripheral and poorly differentiated regions, and lower expression in keratinized and necrotic areas. Notably, expression levels of both Ki-67 and PCNA were markedly reduced in the si-GSEC group compared with the other two groups. Conclusion lncRNA GSEC promotes tumor cell proliferation in vivo in oral squamous cell carcinoma.