Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma
Abstract Background Retroperitoneal liposarcoma (RLPS) is a mesenchymal malignant tumor characterized by different degrees of adipocytic differentiation. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes of RLPS, exhibiting clear dif...
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BMC
2024-12-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-024-03585-x |
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| author | Xiaopeng Wang Jingjing Ye Yan Wu Hongtao Zhang Chengpeng Li Bonan Liu Xiaoya Guan Xiuyun Tian Weiwei Jia Qiao Liu Shuquan Li Rongze Sun Daoning Liu Guoqiang Xue Zhen Wang Liang Yan Ang Lv Jianhui Wu Hui Qiu Chunyi Hao |
| author_facet | Xiaopeng Wang Jingjing Ye Yan Wu Hongtao Zhang Chengpeng Li Bonan Liu Xiaoya Guan Xiuyun Tian Weiwei Jia Qiao Liu Shuquan Li Rongze Sun Daoning Liu Guoqiang Xue Zhen Wang Liang Yan Ang Lv Jianhui Wu Hui Qiu Chunyi Hao |
| author_sort | Xiaopeng Wang |
| collection | DOAJ |
| description | Abstract Background Retroperitoneal liposarcoma (RLPS) is a mesenchymal malignant tumor characterized by different degrees of adipocytic differentiation. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes of RLPS, exhibiting clear differences in biological behaviors and clinical prognosis. The metabolic features and genomic characteristics remain unclear. Methods This study employed lipidomic and RNA-seq analyses of RLPS tissues from 19 WDLPS and 29 DDLPS patients. Western blot and immunohistochemistry staining were performed to verify the tumor tissue protein levels of TIMP1, FN1, MMP11, GPNMB, and ECM1. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate different serum protein levels in 128 blood samples from patients with RLPS. Multivariate analysis was performed to identify the most crucial variables associated with overall survival (OS) and recurrence-free survival (RFS) of the RLPS patients. Results Lipidomic analysis revealed a significant difference in lipid metabolism, particularly in phosphatidylcholines and triacylglycerides metabolism. RNA sequencing analysis revealed that 1,630 differentially expressed genes (DEGs) were significantly enriched in lipid metabolism, developmental process, and extracellular matrix (ECM) pathways. Integrated lipidomic and transcriptomic analysis identified 29 genes as potential biomarkers between WDLPS and DDLPS. Among the 29 DEGs, we found that TIMP1, FN1, MMP11, GPNMB, and ECM1 were increased in DDLPS tumor tissues than in WDLPS tumor tissues. The receiver operating characteristic (ROC) curve showed high specificity and sensitivity in diagnosing patients using a five-gene combination (AUC = 0.904). ELISA revealed a significant increase in the serum levels of ECM1 and GPNMB in patients with DDLPS compared to patients with WDLPS. ECM1 increased progressively across different FNCLCC Grades, correlating negatively with RFS (P = 0.043). GPNMB levels showed a negative correlation with OS (P = 0.019). Conclusions Our study reveals different lipid metabolism, several transcriptional pathways between WDLPS and DDLPS, and examines several serum markers associated with the prognosis of RLPS. These findings provide a vital basis for future endeavors in diagnosing and predicting the prognosis of retroperitoneal liposarcoma with different differentiations. |
| format | Article |
| id | doaj-art-df23e09dc5f0488389932e1f988f02f5 |
| institution | DOAJ |
| issn | 1475-2867 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-df23e09dc5f0488389932e1f988f02f52025-08-20T02:40:17ZengBMCCancer Cell International1475-28672024-12-0124111710.1186/s12935-024-03585-xIntegrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcomaXiaopeng Wang0Jingjing Ye1Yan Wu2Hongtao Zhang3Chengpeng Li4Bonan Liu5Xiaoya Guan6Xiuyun Tian7Weiwei Jia8Qiao Liu9Shuquan Li10Rongze Sun11Daoning Liu12Guoqiang Xue13Zhen Wang14Liang Yan15Ang Lv16Jianhui Wu17Hui Qiu18Chunyi Hao19Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteTrauma Treatment Center, Peking University People’s Hospital; Key Laboratory of Trauma Treatment and Neural Regeneration (Peking University), National Center for Trauma MedicineKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & InstituteGuowen (Changchun) International HospitalKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & InstituteAbstract Background Retroperitoneal liposarcoma (RLPS) is a mesenchymal malignant tumor characterized by different degrees of adipocytic differentiation. Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are two of the most common subtypes of RLPS, exhibiting clear differences in biological behaviors and clinical prognosis. The metabolic features and genomic characteristics remain unclear. Methods This study employed lipidomic and RNA-seq analyses of RLPS tissues from 19 WDLPS and 29 DDLPS patients. Western blot and immunohistochemistry staining were performed to verify the tumor tissue protein levels of TIMP1, FN1, MMP11, GPNMB, and ECM1. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate different serum protein levels in 128 blood samples from patients with RLPS. Multivariate analysis was performed to identify the most crucial variables associated with overall survival (OS) and recurrence-free survival (RFS) of the RLPS patients. Results Lipidomic analysis revealed a significant difference in lipid metabolism, particularly in phosphatidylcholines and triacylglycerides metabolism. RNA sequencing analysis revealed that 1,630 differentially expressed genes (DEGs) were significantly enriched in lipid metabolism, developmental process, and extracellular matrix (ECM) pathways. Integrated lipidomic and transcriptomic analysis identified 29 genes as potential biomarkers between WDLPS and DDLPS. Among the 29 DEGs, we found that TIMP1, FN1, MMP11, GPNMB, and ECM1 were increased in DDLPS tumor tissues than in WDLPS tumor tissues. The receiver operating characteristic (ROC) curve showed high specificity and sensitivity in diagnosing patients using a five-gene combination (AUC = 0.904). ELISA revealed a significant increase in the serum levels of ECM1 and GPNMB in patients with DDLPS compared to patients with WDLPS. ECM1 increased progressively across different FNCLCC Grades, correlating negatively with RFS (P = 0.043). GPNMB levels showed a negative correlation with OS (P = 0.019). Conclusions Our study reveals different lipid metabolism, several transcriptional pathways between WDLPS and DDLPS, and examines several serum markers associated with the prognosis of RLPS. These findings provide a vital basis for future endeavors in diagnosing and predicting the prognosis of retroperitoneal liposarcoma with different differentiations.https://doi.org/10.1186/s12935-024-03585-xRetroperitoneal liposarcomaBiomarkerLipidomicsRNA sequencing |
| spellingShingle | Xiaopeng Wang Jingjing Ye Yan Wu Hongtao Zhang Chengpeng Li Bonan Liu Xiaoya Guan Xiuyun Tian Weiwei Jia Qiao Liu Shuquan Li Rongze Sun Daoning Liu Guoqiang Xue Zhen Wang Liang Yan Ang Lv Jianhui Wu Hui Qiu Chunyi Hao Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma Cancer Cell International Retroperitoneal liposarcoma Biomarker Lipidomics RNA sequencing |
| title | Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma |
| title_full | Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma |
| title_fullStr | Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma |
| title_full_unstemmed | Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma |
| title_short | Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma |
| title_sort | integrated lipidomics and rna seq reveal prognostic biomarkers in well differentiated and dedifferentiated retroperitoneal liposarcoma |
| topic | Retroperitoneal liposarcoma Biomarker Lipidomics RNA sequencing |
| url | https://doi.org/10.1186/s12935-024-03585-x |
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