Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma

Xiaopeng Wang ¹, Jingjing Ye ², Yan Wu ³

⁰Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing, 100142, P. R. China.

Cancer Cell International +

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December 19, 2024

View abstract on PubMed

Summary

This study reveals distinct lipid metabolism and gene expression in retroperitoneal liposarcoma (RLPS) subtypes, identifying potential biomarkers for diagnosis and prognosis in well-differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma.

Area Of Science

Oncology
Molecular Biology
Biochemistry

Background

Retroperitoneal liposarcoma (RLPS) encompasses subtypes like well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS), which differ in behavior and prognosis.
The precise metabolic and genomic characteristics distinguishing these RLPS subtypes remain largely uncharacterized.

Purpose Of The Study

To investigate the distinct lipidomic and transcriptomic profiles of WDLPS and DDLPS.
To identify potential molecular biomarkers for differentiating RLPS subtypes and predicting patient outcomes.

Main Methods

Lipidomic and RNA-sequencing analyses were performed on RLPS tissue samples from 19 WDLPS and 29 DDLPS patients.
Protein expression of key genes (TIMP1, FN1, MMP11, GPNMB, ECM1) was validated using Western blot and immunohistochemistry.
Serum protein levels were assessed via ELISA in 128 RLPS patients, with multivariate analysis correlating markers with overall survival (OS) and recurrence-free survival (RFS).

Main Results

Significant differences in lipid metabolism, particularly phosphatidylcholines and triacylglycerides, were observed between WDLPS and DDLPS.
RNA-seq identified 1,630 differentially expressed genes enriched in lipid metabolism, developmental, and extracellular matrix pathways.
A five-gene signature (TIMP1, FN1, MMP11, GPNMB, ECM1) showed high diagnostic accuracy (AUC=0.904). Increased ECM1 and GPNMB serum levels correlated with poorer RFS and OS, respectively.

Conclusions

Distinct lipid metabolism and transcriptional pathways differentiate WDLPS from DDLPS.
Serum levels of ECM1 and GPNMB serve as potential prognostic markers for RLPS.
These findings offer a foundation for improved diagnostic and prognostic strategies for RLPS subtypes.

Keywords:

Biomarker Lipidomics RNA sequencing Retroperitoneal liposarcoma

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