FBXO39 predicts poor prognosis and correlates with tumor progression in cervical squamous cell carcinoma.

ABSTRACT

BACKGROUND: Cancer/testis antigen (CTA) is a class of antigen molecules mainly expressed in the germinal epithelium of testis and some tumor tissues. FBXO39, also known as F-box protein 39, is a crucial CTA molecule. F-box protein 39 (FBXO39) is overexpressed in cervical squamous cell carcinomas (CESCs), however its function in cancer development and clinical significance are still unknown. METHODS: We used paraffin-embedded tumor tissues from 124 patients and fresh-harvested and paired adjacent normal esophageal tissues from 15 CESC patients who underwent primary surgical resection in Xijing Hospital between 2015 and 2020. The expression level of FBXO39 was evaluated through immunohistochemistry, Western Blot and q-PCR. Prognostic and survival analyses were conducted using univariate/multivariate analysis and log-rank analysis with SPSS 23.0. CCK-8, wound-healing and Transwell assays were applied to demonstrate that FBXO39 promoted the proliferation, migration and invasion. Finally, we constructed a xenografts model of the C-33A cell lines to observe the effect of FBXO39 on tumorigenesis in vivo. RESULTS: Immunohistochemical results showed that FBXO39 was highly expressed in cancer tissues than in corresponding non-cancer tissues. Similarly, we proved this result at protein and mRNA level by Western-Blotting and q-PCR. Prognostic and OS analyses showed that the FBXO39 expression level was an individual prognostic factor in CESC patients. CCK-8, wound-healing and Transwell assays proved that the overexpression of FBXO39 in Si-Ha cells promoted the proliferation, migration and invasion of the cells. Knocking down FBXO39 in C-33A cells inhibited the proliferation, migration and invasion of cells. The experimental results of xenografts model in nude mice showed that the knockdown of FBXO39 in C-33A cells slowed down the growth of tumor. CONCLUSION: FBXO39 is a poor prognostic factor of cervical squamous cell carcinoma, which may provide a novel therapeutic target for CESC.