Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis
Abstract Background Colon adenocarcinoma (COAD) is increasingly prevalent among patients under 50 years old, and the 5-year survival rate for patients with metastasis is less than 20%. Identifying significant biomarkers and therapeutic targets is crucial. We investigated the expression of LRP2 in CO...
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Springer
2025-05-01
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| Online Access: | https://doi.org/10.1007/s12672-025-02568-2 |
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| author | Jie Zhang Ziyun Liu Xiaoqing Ma Zhenyu Shi Jing Zhao Yongjie Xie Xiaobin Shang Xia Zhang |
| author_facet | Jie Zhang Ziyun Liu Xiaoqing Ma Zhenyu Shi Jing Zhao Yongjie Xie Xiaobin Shang Xia Zhang |
| author_sort | Jie Zhang |
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| description | Abstract Background Colon adenocarcinoma (COAD) is increasingly prevalent among patients under 50 years old, and the 5-year survival rate for patients with metastasis is less than 20%. Identifying significant biomarkers and therapeutic targets is crucial. We investigated the expression of LRP2 in COAD and its prognostic value utilizing single-cell sequencing and transcriptomics datasets, which was conducted preliminary validation at the patient samples and cellular levels as well. Methods Based on differential gene expression of tumor samples and normal tissues in The Cancer Genome Atlas (TCGA), we performed consensus clustering, univariate and multivariate Cox regression analysis applying 1,234 mitochondrial metabolism-related genes (MMRGs) to identify some essential genes associated with poor prognosis in COAD patients. We validated survival outcome and biological function of the target gene leveraging single-cell sequencing and transcriptomics datasets from Gene Expression Omnibus (GEO), and evaluated the value of the target gene in the clinical pathology stage of COAD patients. Simultaneously, the expression levels of critical gene were detected in the diverse tissues of COAD by immunohistochemistry (IHC) staining. Transcriptomics data was continuously implemented to compare the discrepancy between the expression levels of the target gene and somatic mutation burden, inspecting the key pathways of the target gene by gene set enrichment analysis (GSEA) and examining its drug sensitivity synthetically in the CellMiner databases. The proliferative capacity augmented in LRP2-overexpressed colon cancer cells was determined employing cell counting kit-8 (CCK-8) and flow cytometry assays. Results LRP2 served as a key mitochondrial metabolism-related gene was assessed clinical prognosis in COAD patients according to the TCGA database. High expression of LRP2 was prominently associated with poor prognosis in COAD patients (P < 0.05), which was validated by GEO databases, and the expression levels of LRP2 were positively related to clinical pathological stage simultaneously (P < 0.05). Some specific cell types were clustered and proliferation pathways were immensely enriched, which were correlated with LRP2 in two single-cell sequencing datasets. The mutation profiles displayed remarkable differences in two levels of LRP2, we also observed high expressions of LRP2 were immensely correlated with high tumor mutation burden (TMB) and unfavorable prognosis in these patients (P < 0.05). LRP2 was significantly enriched in multiple cancer proliferation-related pathways, and the noteworthy correlation between LRP2 and the sensitivity to various drugs was identified (P < 0.05). The expression levels of LRP2 were multifarious in different COAD patients based on IHC staining. LRP2-overpression could stimulate the proliferation capability of HCT116 and SW480 cell lines markedly (P < 0.05). Conclusion The expression levels of LRP2 were intimately correlated with gene mutations, prognosis, pathological stage and the sensitivity to anticancer drugs in COAD. Augmented levels of LRP2 would manifest poor prognosis, which furnished novel insights for clinical diagnosis and treatment in COAD. LRP2 could extensively facilitate the proliferation ability of colon cell lines. |
| format | Article |
| id | doaj-art-e00d9c0ea14a4b9eb4aae12b71b09f47 |
| institution | OA Journals |
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| publishDate | 2025-05-01 |
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| series | Discover Oncology |
| spelling | doaj-art-e00d9c0ea14a4b9eb4aae12b71b09f472025-08-20T01:51:36ZengSpringerDiscover Oncology2730-60112025-05-0116111910.1007/s12672-025-02568-2Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysisJie Zhang0Ziyun Liu1Xiaoqing Ma2Zhenyu Shi3Jing Zhao4Yongjie Xie5Xiaobin Shang6Xia Zhang7Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical UniversityDepartment of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Minimally Invasive Esophageal Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerDepartment of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for CancerAbstract Background Colon adenocarcinoma (COAD) is increasingly prevalent among patients under 50 years old, and the 5-year survival rate for patients with metastasis is less than 20%. Identifying significant biomarkers and therapeutic targets is crucial. We investigated the expression of LRP2 in COAD and its prognostic value utilizing single-cell sequencing and transcriptomics datasets, which was conducted preliminary validation at the patient samples and cellular levels as well. Methods Based on differential gene expression of tumor samples and normal tissues in The Cancer Genome Atlas (TCGA), we performed consensus clustering, univariate and multivariate Cox regression analysis applying 1,234 mitochondrial metabolism-related genes (MMRGs) to identify some essential genes associated with poor prognosis in COAD patients. We validated survival outcome and biological function of the target gene leveraging single-cell sequencing and transcriptomics datasets from Gene Expression Omnibus (GEO), and evaluated the value of the target gene in the clinical pathology stage of COAD patients. Simultaneously, the expression levels of critical gene were detected in the diverse tissues of COAD by immunohistochemistry (IHC) staining. Transcriptomics data was continuously implemented to compare the discrepancy between the expression levels of the target gene and somatic mutation burden, inspecting the key pathways of the target gene by gene set enrichment analysis (GSEA) and examining its drug sensitivity synthetically in the CellMiner databases. The proliferative capacity augmented in LRP2-overexpressed colon cancer cells was determined employing cell counting kit-8 (CCK-8) and flow cytometry assays. Results LRP2 served as a key mitochondrial metabolism-related gene was assessed clinical prognosis in COAD patients according to the TCGA database. High expression of LRP2 was prominently associated with poor prognosis in COAD patients (P < 0.05), which was validated by GEO databases, and the expression levels of LRP2 were positively related to clinical pathological stage simultaneously (P < 0.05). Some specific cell types were clustered and proliferation pathways were immensely enriched, which were correlated with LRP2 in two single-cell sequencing datasets. The mutation profiles displayed remarkable differences in two levels of LRP2, we also observed high expressions of LRP2 were immensely correlated with high tumor mutation burden (TMB) and unfavorable prognosis in these patients (P < 0.05). LRP2 was significantly enriched in multiple cancer proliferation-related pathways, and the noteworthy correlation between LRP2 and the sensitivity to various drugs was identified (P < 0.05). The expression levels of LRP2 were multifarious in different COAD patients based on IHC staining. LRP2-overpression could stimulate the proliferation capability of HCT116 and SW480 cell lines markedly (P < 0.05). Conclusion The expression levels of LRP2 were intimately correlated with gene mutations, prognosis, pathological stage and the sensitivity to anticancer drugs in COAD. Augmented levels of LRP2 would manifest poor prognosis, which furnished novel insights for clinical diagnosis and treatment in COAD. LRP2 could extensively facilitate the proliferation ability of colon cell lines.https://doi.org/10.1007/s12672-025-02568-2Colon cancerPrognosisLRP2Multi-omicsCell proliferation |
| spellingShingle | Jie Zhang Ziyun Liu Xiaoqing Ma Zhenyu Shi Jing Zhao Yongjie Xie Xiaobin Shang Xia Zhang Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis Discover Oncology Colon cancer Prognosis LRP2 Multi-omics Cell proliferation |
| title | Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis |
| title_full | Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis |
| title_fullStr | Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis |
| title_full_unstemmed | Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis |
| title_short | Deciphering the interaction between the expression of LRP2 served as a mitochondrial metabolism-related gene and prognosis in colon cancer integrating multi-omics analysis |
| title_sort | deciphering the interaction between the expression of lrp2 served as a mitochondrial metabolism related gene and prognosis in colon cancer integrating multi omics analysis |
| topic | Colon cancer Prognosis LRP2 Multi-omics Cell proliferation |
| url | https://doi.org/10.1007/s12672-025-02568-2 |
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