TM4SF1 as a Prognostic Biomarker and Therapeutic Target in Cervical Cancer

Abstract

Objective

Accumulating evidence suggests that transmembrane 4 L6 family member 1 (TM4SF1) is associated with the development of various cancers; yet comprehensive studies on TM4SF1 in cervical cancer are lacking. Therefore, we aimed to evaluate the prognostic value of TM4SF1 in cervical cancer, elucidate its potential oncogenic functions in this disease, and further explore its feasibility as a therapeutic target.

Methods

The expression profiles and clinical information of cervical cancer patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression levels of TM4SF1 were compared between cervical cancer and normal cervical tissues using the Wilcoxon rank-sum test. Kaplan–Meier analysis was employed to assess the prognostic value of TM4SF1. Furthermore, functional enrichment analyses were performed to explore the associated signaling pathways and biological functions. The methylation status of TM4SF1 was analyzed using the UALCAN and MethSurv databases. In addition, in vitro experiments were conducted to preliminarily validate the role and mechanisms of TM4SF1 in cervical cancer.

Results

TM4SF1 was overexpressed in nearly all tumors, and its overexpression was associated with poor prognosis in cervical cancer. Moreover, the correlation between TM4SF1 expression and the expression of immune cell infiltration markers and immune checkpoint genes suggested that it had potential applications in cancer immunotherapy. Western blot analysis and immunohistochemistry revealed significantly elevated protein levels of TM4SF1 in cervical cancer tissues and cells. Further studies revealed that the knockdown of TM4SF1 significantly inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of HeLa and SiHa cells, as well as promoted their apoptosis.

Conclusion

TM4SF1 may serve as a potential prognostic biomarker and therapeutic target for cervical cancer.

Keywords

Transmembrane 4 L6 family member 1 (TM4SF1) / Cervical cancer / Biomarker / Therapeutic target / Invasion and migration / Epithelial-mesenchymal transition (EMT) / Immunotherapy / DNA methylation

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Funding

Natural Science Foundation of Hubei Province(2022CFC019)

RIGHTS & PERMISSIONS

The Author(s), under exclusive licence to the Huazhong University of Science and Technology