A Novel Defined Necroptosis-Related Genes Prognostic Signature for Predicting Prognosis and Treatment of Osteosarcoma

Overview

Journal Biochem Genet

Specialty Molecular Biology

Date 2023 Jul 17

PMID 37460861

Authors

Shibing Zhao

Tao Wang

Fei Huang

Qingzhong Zhao

Deliang Gong

Jun Liu

Chengfeng Yi

Shuai Liang

Erbao Bian

Dasheng Tian

Juehua Jing

Affiliations

Soon will be listed here.

Abstract

Osteosarcoma (OS) is a frequent primary malignant bone tumor, with a poor prognosis. Necroptosis is strongly correlated with OS and may be an influential target for treating OS. This study's objective was to establish a necroptosis-related gene (NRG) prognostic signature that could predict OS prognosis and guide OS treatment. First, we identified 20 NRGs associated with OS survival based on the TARGET database. We then derived a 7 NRG prognostic signature. Our findings revealed that the 7 NRG prognostic signature performed well in predicting the survival of OS patients. We next analyzed differences in immunological status and immune cell infiltration. In addition, we examined the relationship between chemo/immunotherapeutic response and the 7-NRG prognostic signature. In addition, to probe the mechanisms underlying the NRG prognostic signature, we performed functional enrichment assays including GO and KEGG. Finally, CHMP4C was selected for functional experiments. Silencing CHMP4C prevented OS cells from proliferating, migrating, and invading. This 7-NRG prognostic signature seems to be an excellent predictor that can provide a fresh direction for OS treatment.

Citing Articles

The role and mechanism of CHMP4C in poor prognosis and drug sensitivity of lung adenocarcinoma.

Xu C, Liu M, Li Y, Peng X, Zhou W, Zhang W Discov Oncol. 2025; 16(1):270.

PMID: 40050481 PMC: 11885760. DOI: 10.1007/s12672-025-01986-6.

References

Baeten C, Castermans K, Hillen H, Griffioen A . Proliferating endothelial cells and leukocyte infiltration as prognostic markers in colorectal cancer. Clin Gastroenterol Hepatol. 2006; 4(11):1351-7. DOI: 10.1016/j.cgh.2006.08.005. View

Buddingh E, Kuijjer M, Duim R, Burger H, Agelopoulos K, Myklebost O . Tumor-infiltrating macrophages are associated with metastasis suppression in high-grade osteosarcoma: a rationale for treatment with macrophage activating agents. Clin Cancer Res. 2011; 17(8):2110-9. DOI: 10.1158/1078-0432.CCR-10-2047. View

Cersosimo F, Lonardi S, Bernardini G, Telfer B, Mandelli G, Santucci A . Tumor-Associated Macrophages in Osteosarcoma: From Mechanisms to Therapy. Int J Mol Sci. 2020; 21(15). PMC: 7432207. DOI: 10.3390/ijms21155207. View

Chen C, Xie L, Ren T, Huang Y, Xu J, Guo W . Immunotherapy for osteosarcoma: Fundamental mechanism, rationale, and recent breakthroughs. Cancer Lett. 2020; 500:1-10. DOI: 10.1016/j.canlet.2020.12.024. View

Chen Y, Liu Y, Wang M . Identification of a Pyroptosis-Related Gene Signature and Effect of Silencing the and in Pancreatic Adenocarcinoma. Int J Gen Med. 2022; 15:3199-3213. PMC: 8943832. DOI: 10.2147/IJGM.S353849. View

Clara J, Monge C, Yang Y, Takebe N . Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol. 2019; 17(4):204-232. DOI: 10.1038/s41571-019-0293-2. View

Teterycz P, Czarnecka A, Indini A, Spalek M, Labianca A, Rogala P . Multimodal Treatment of Advanced Mucosal Melanoma in the Era of Modern Immunotherapy. Cancers (Basel). 2020; 12(11). PMC: 7692305. DOI: 10.3390/cancers12113131. View

Dai E, Meng L, Kang R, Wang X, Tang D . ESCRT-III-dependent membrane repair blocks ferroptosis. Biochem Biophys Res Commun. 2019; 522(2):415-421. PMC: 6957708. DOI: 10.1016/j.bbrc.2019.11.110. View

Degterev A, Huang Z, Boyce M, Li Y, Jagtap P, Mizushima N . Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol. 2006; 1(2):112-9. DOI: 10.1038/nchembio711. View

10.

Eaton B, Schwarz R, Vatner R, Yeh B, Claude L, Indelicato D . Osteosarcoma. Pediatr Blood Cancer. 2020; 68 Suppl 2:e28352. DOI: 10.1002/pbc.28352. View

11.

Fritzsching B, Fellenberg J, Moskovszky L, Sapi Z, Krenacs T, Machado I . CD8/FOXP3-ratio in osteosarcoma microenvironment separates survivors from non-survivors: a multicenter validated retrospective study. Oncoimmunology. 2015; 4(3):e990800. PMC: 4404826. DOI: 10.4161/2162402X.2014.990800. View

12.

Gao W, Wang X, Zhou Y, Wang X, Yu Y . Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy. Signal Transduct Target Ther. 2022; 7(1):196. PMC: 9208265. DOI: 10.1038/s41392-022-01046-3. View

13.

Gong Y, Guy C, Olauson H, Becker J, Yang M, Fitzgerald P . ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences. Cell. 2017; 169(2):286-300.e16. PMC: 5443414. DOI: 10.1016/j.cell.2017.03.020. View

14.

Gong Y, Fan Z, Luo G, Yang C, Huang Q, Fan K . The role of necroptosis in cancer biology and therapy. Mol Cancer. 2019; 18(1):100. PMC: 6532150. DOI: 10.1186/s12943-019-1029-8. View

15.

Guo Y, Shang A, Wang S, Wang M . Multidimensional Analysis of CHMP Family Members in Hepatocellular Carcinoma. Int J Gen Med. 2022; 15:2877-2894. PMC: 8923641. DOI: 10.2147/IJGM.S350228. View

16.

Heymann M, Lezot F, Heymann D . The contribution of immune infiltrates and the local microenvironment in the pathogenesis of osteosarcoma. Cell Immunol. 2017; 343:103711. DOI: 10.1016/j.cellimm.2017.10.011. View

17.

Hong J, Li Q, Wang X, Li J, Ding W, Hu H . Development and validation of apoptosis-related signature and molecular subtype to improve prognosis prediction in osteosarcoma patients. J Clin Lab Anal. 2022; 36(7):e24501. PMC: 9280000. DOI: 10.1002/jcla.24501. View

18.

Hoshida Y, Brunet J, Tamayo P, Golub T, Mesirov J . Subclass mapping: identifying common subtypes in independent disease data sets. PLoS One. 2007; 2(11):e1195. PMC: 2065909. DOI: 10.1371/journal.pone.0001195. View

19.

Jiang P, Gu S, Pan D, Fu J, Sahu A, Hu X . Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response. Nat Med. 2018; 24(10):1550-1558. PMC: 6487502. DOI: 10.1038/s41591-018-0136-1. View

20.

Joo M, Kang Y, Yoo C, Cha S, Chung Y . Prognostic significance of chemotherapy-induced necrosis in osteosarcoma patients receiving pasteurized autografts. PLoS One. 2017; 12(2):e0172155. PMC: 5308815. DOI: 10.1371/journal.pone.0172155. View