TSPAN9 inhibits malignant progression of hepatocellular carcinoma

Background: Tetraspanins (TSPANs) are a critical family for cell migration, which have been implicated in a variety of activities including Cancer. Previous study showed that tetraspanin 9 (TSPAN9) plays an important role in gastric Cancer. In this study, we aim to explore the biological functions of TSPAN9 in hepatocellular carcinoma (HCC).

Methods: The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to analyze TSPAN9 expression, prognostic mutations, somatic copy number alterations (sCNAs), and tumor immune characteristics in 33 tumors. Immunohistochemistry images of TSPAN9 in HCC tissues were obtained from the Human Protein Atlas (HPA) database. Survival curves were generated using the Kaplan-Meier Plotter database. The proliferation, migration, and invasion abilities of HCC cells were assessed using Cell Counting Kit-8 (CCK-8), wound healing, and Transwell assays.

Results: TSPAN9 was deregulated in various tumor types, and its expression was lower in HCC tissues than that of normal liver tissues (P<0.05). Moreover, TSPAN9 expression had a correlation with the prognosis of tumor patients, and HCC patients with low TSPAN9 expression showed a poor prognosis (Log-rank P<0.05). In addition, we detected that TSPAN9 was significantly decreased in HCC cells (P<0.01). As compared to the control cells, overexpression of TSPAN9 in HCC cells significantly reduced cell proliferation, slowed the wound healing rate, and inhibited the invasive and migration ability (all P<0.05). TCGA database analysis revealed a relationship between the expression of TSPAN9 and epithelium-mesenchymal transformation (EMT) factors.

Conclusions: Downregulated expression of TSPAN9 indicates a poor prognosis of HCC patients. TSPAN9 can inhibit the proliferation and metastasis of HCC cells.

Hepatocellular carcinoma (HCC); metastasis; prognosis; proliferation; tetraspanin 9 (TSPAN9).