Low Level FLT3LG is a Novel Poor Prognostic Biomarker for Cervical Cancer with Immune Infiltration

J Inflamm Res. 2022 Oct 19:15:5889-5904. doi: 10.2147/JIR.S384908. eCollection 2022.

Abstract

Introduction: The FMS-related tyrosine kinase 3 (FLT3) ligand (FLT3LG), a growth factor, binds to FLT3 on dendritic cell (DCs) to enhance their differentiation and expansion. It has shown great potential as an immunotherapy target for cancers. However, the expression and function of FLT3LG in cervical cancer remain largely unknown.

Materials and methods: In this study, we obtained the expression of FLT3LG, the clinical prognosis in cervical cancer, via multiple databases, including The Cancer Genome Atlas (TCGA), the TISIDB database, and Tumor Immune Estimate Resource (TIMER). The results were further investigated using real-time quantitative PCR (qPCR) cytology specimens in 489 patients. Furthermore, Kaplan-Meier Cox regression and prognostic nomogram analyses were used to assess FLT3LG's clinical significance in cervical cancer patients. All calculations used the R package.

Results: As a result, FLT3LG expression decreased in cervical cancer compared with standard samples. And the low expression of FLT3LG was associated with a poor prognosis. Furthermore, Receiver Operating Characteristics (ROC) analysis indicated that FLT3LG might serve as a valuable diagnostic biomarker for cervical cancer. Additionally, it indicated that the FLT3LG had the highest odds ratio (OR=10.519; (7.371-27.071)) for detecting CIN 2+. In addition, our result also demonstrated that expression of FLT3LG was closely related to immune cells, immune inhibitors, immunostimulators, receptors, and chemokines in CESC.

Conclusion: Research on FLT3LG provided insight into its critical function. Hence, the low expression of FLT3LG may be a valuable biomarker in CESC patients linked with immune infiltration.

Keywords: FLT3LG; cervical cancer; immune cells; immunotherapy; prognosis; tumor-infiltrating.

Grants and funding

This work was funded by grants from the National Natural Science Foundation of China (Nos. 81772783, 81971475).