# The Prognostic Value and Immunomodulatory Role of Spsb2, a Novel Immune Checkpoint Molecule, in Hepatocellular Carcinoma

## TL;DR

This study explores SPSB2, a new immune checkpoint molecule, and finds it is linked to worse outcomes and immune responses in liver cancer patients.

## Contribution

The study identifies SPSB2 as a novel immune checkpoint molecule with prognostic value in hepatocellular carcinoma.

## Key findings

- Higher SPSB2 expression correlates with poorer prognosis and multiple clinical indicators in LIHC patients.
- SPSB2 is enriched in tumorigenesis and immune-related pathways and is linked to immune cells and checkpoints.
- Knockdown of SPSB2 inhibits cancer cell proliferation, invasion, and metastasis in liver cancer cell lines.

## Abstract

Background: Liver cancer, specifically hepatocellular carcinoma (LIHC), ranks as the second most common cause of cancer-related fatalities globally. Moreover, the occurrence rate of LIHC is steadily increasing. A recently identified gene, SPSB2, has been implicated in cell signaling, impacting the development and progression of non-small cell lung cancer. Nevertheless, studies on the role of SPSB2 in the pathogenesis of LIHC are lacking. Methods: Using the TCGA, GTEx, and GEO databases, we obtained differentially expressed genes that affect the prognosis of patients with LIHC. We utilized the Kruskal–Wallis test, along with univariate and multivariate COX regression analyses, to determine the correlation between SPSB2 and patient clinical indicators. Potential biological functions of SPSB2 in LIHC were explored by enrichment analysis, ssGSEA, and Spearman correlation analysis. Finally, LIHC cell lines Huh7 and SMMC-7721 were used to validate the biological function of SPSB2. Results: The results showed LIHC patients with higher SPSB2 expression had a poorer prognosis, and SPSB2 expression was significantly correlated with LIHC patients’ Histologic grade, Pathologic T stage, Prothrombin time, Pathologic stage, BMI, weight, adjacent hepatic tissue inflammation, AFP level, and OS event (p < 0.05). SPSB2 shows notable enrichment in pathways linked to tumorigenesis and the immune system. Moreover, its expression is strongly connected to immune cells and immune checkpoints. Knockdown of SPSB2 expression in Huh7 cells and SMMC-7721 cells inhibits SPSB2’s biological functions, including proliferation, invasion, metastasis, and other phenotypes. Conclusions: SPSB2 plays a crucial role in the development of LIHC. It is related to the immune response and unfavorable outcomes. SPSB2 may function as a clinical biomarker for prognosis.