KLHL17 as a Prognostic Indicator and Therapeutic Target in Cervical Cancer: A Comprehensive Analysis.

INTRODUCTION

This study aims to clarify the role of kelch like family member 17 (KLHL17) in cervical cancer (CESC) is unclear.

OBJECTIVE

To clarify this uncertainty, our research employed bioinformatics analysis coupled with experimental corroboration.

METHODS

We utilized the Cancer Genome Atlas (TCGA) database to assess the expression of KLHL17 in various cancers, specifically CESC, and to explore its association with clinical characteristics, diagnostic utility, and prognostic significance in CESC. The current investigation delved into the potential regulatory pathways related to KLHL17, examining its connection with the infiltration of immune cells, the expression of immune checkpoint genes, the status of microsatellite instability (MSI), and the efficacy of diverse therapeutic agents in CESC. The research analyzed KLHL17 expression patterns using single-cell sequencing data from CESC samples and investigated the genetic variations of KLHL17 within this context. KLHL17 expression was validated using GSE145372. The presence and levels of KLHL17 in different cell lines were validated through quantitative real-time PCR (qRT-PCR) assays.

RESULTS

KLHL17 exhibited irregular expression profiles across various cancer types, including CESC. Furthermore, increased KLHL17 levels in CESC patients were significantly associated with a lower progression-free survival (PFS) rate (hazard ratio: 1.62; 95% confidence interval: 1.01-2.60, p = 0.044). Moreover, KLHL17 expression emerged as a distinct prognostic indicator for CESC patients (p = 0.031). It has been associated with various biological pathways, such as cytokine-cytokine receptor interaction, primary immunodeficiency, cell adhesion molecules (CAMs), chemokine signaling pathway, steroid hormone biosynthesis, and others. The expression levels of KLHL17 were found to correlate with the presence of immune cells, the expression of immune checkpoint genes, and the status of MSI within CESC. Furthermore, KLHL17 expression exhibited a significant and inverse correlation with XMD15-27, rTRAIL, Paclitaxel, tp4ek, and tp4ek-k6. Furthermore, KLHL17 was found to be significantly positively regulated in CESC cell lines.

DISCUSSION: The findings suggest that KLHL17 is involved in the progression of CESC and may serve as a potential prognostic marker and therapeutic target. KLHL17's association with immune cell infiltration and immune checkpoint genes indicates a role in immuneevasion. Future research should focus on validating these findings through independent datasets and experimental studies to elucidate the molecular mechanisms underlying KLHL17's role in CESC progression and immune regulation.

CONCLUSION

KLHL17 is a promising prognostic marker and potential therapeutic target in CESC.