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

Yanru Yang; Yun Zhao; Guorui Sun; Saijie Zuo; Jia Chai; Tianqi Xu; Jin Liu; Lingfei Li; Junyang Song; Shoubin Qian; Yulin Kang; Fang Sui; Mingyang Li; Qingge Jia

doi:10.1016/j.prp.2022.154090

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

Pathol Res Pract. 2022 Oct:238:154090. doi: 10.1016/j.prp.2022.154090. Epub 2022 Aug 28.

Authors

Yanru Yang¹, Yun Zhao², Guorui Sun¹, Saijie Zuo³, Jia Chai¹, Tianqi Xu¹, Jin Liu¹, Lingfei Li¹, Junyang Song¹, Shoubin Qian¹, Yulin Kang⁴, Fang Sui⁵, Mingyang Li⁶, Qingge Jia⁷

Affiliations

¹ State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
² Military medicine and special subject, No. 971 hospital of the PLA Navy, Qingdao, China.
³ School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, China.
⁴ Institute of Environmental Information, Chinese Research academy of Environmental Sciences, Beijing, China. Electronic address: kangyulin@craes.org.cn.
⁵ Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address: sf_brighteyes@163.com.
⁶ State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi'an, China. Electronic address: limingyang1108@sina.com.
⁷ Department of Reproductive Endocrinology, Xi'an International Medical Center, Northwest University, Xi'an, China. Electronic address: 361400283@qq.com.

PMID: 36049441
DOI: 10.1016/j.prp.2022.154090

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.

Keywords: Cervical squamous cell carcinoma; FBXO39; Prognostic factor.