Unveiling SSR4: A Promising Biomarker in Esophageal Squamous Cell Carcinoma

Jiaqi Zhang ¹ Fang Jia ^1* Chuqiao Li ² Shunzhe Song ^1* Aixia Gong ^1*

• ¹ Department of Digestive Endoscopy, The First Affiliated Hospital of Dalian Medical University, Dalian, China
• ² Department of Gastroenterology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China

Background: Esophageal squamous cell carcinoma (ESCC) represents a frequent cancer with a poor prognosis. Altered glucose metabolism contributes factor to ESCC progression. In our previous study, signal sequence receptor subunit delta (SSR4) was included in an ESCC prognostic model; however, the mechanisms underlying SSR4 implication in ESCC remain ambiguous. Accordingly, we aim to determine the interconnection between SSR4 expression and clinical characteristics of ESCC.Methods: This differential expression and prognostic significance of SSR4 was performed using bulk RNA-seq data and 110 patients with complete follow-up information. The ESCC cell subsets with the highest gene expression levels were identified with single-cell data. Gene function and enrichment, immune infiltration, cell communication, and molecular docking analyses were performed.Results: Unlike adjacent non-cancerous tissues, SSR4 was overexpressed in ESCC tissues, validated by both reverse transcription-qPCR and IHC staining. SSR4 expression was related to the N stage, lymph node metastasis, and AJCC TNM classification stage. Patients exhibiting low SSR4 expression had a more favorable prognosis. The highest SSR4 expression was recognized in tumor plasma cells. Continued exploration of immune infiltration highlighted a close association between SSR4 gene expression and the infiltration of immune cells such as plasma cells. On dividing cells into SSR4positive and -negative groups, CellChat analysis indicated that SSR4 may regulate the interactions that existed between ESCC tumor plasma cells and the tumor microenvironment (TME) by modulating the MIF/CD74/CXCR4 axis. Conclusion: The SSR4 gene may have significant relevance with clinical pathological factors, and play a critical role in the regulation of tumor microenvironment of ESCC patients. Overall, SSR4 may be a promising ESCC biomarker with prospective applicability in clinical diagnosis as well as the development of targeted treatment approaches in patients of ESCC.