Development of a Novel Disulfidptosis-related LncRNA Signature for Prognostic and Immune Response Prediction in Clear Cell Renal Cell Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2024 Jan 5

PMID 38182642

Authors

Ning Wang

Yifeng Hu

Shasha Wang

Qin Xu

Xiaojing Jiao

Yanliang Wang

Lei Yan

Huixia Cao

Fengmin Shao

Affiliations

Soon will be listed here.

Abstract

Disulfidptosis, a novel form of regulated cell death, occurs due to the aberrant accumulation of intracellular cystine and other disulfides. Moreover, targeting disulfidptosis could identify promising approaches for cancer treatment. Long non-coding RNAs (lncRNAs) are known to be critically implicated in clear cell renal cell carcinoma (ccRCC) development. Currently, the involvement of disulfidptosis-related lncRNAs in ccRCC is yet to be elucidated. This study primarily dealt with identifying and validating a disulfidptosis-related lncRNAs-based signature for predicting the prognosis and immune landscape of individuals with ccRCC. Clinical and RNA sequencing data of ccRCC samples were accessed from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was conducted for the identification of the disulfidptosis-related lncRNAs. Additionally, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator Cox regression, and stepwise multivariate Cox analysis were executed to develop a novel risk prognostic model. The prognosis-predictive capacity of the model was then assessed using an integrated method. Variation in biological function was noted using GO, KEGG, and GSEA. Additionally, immune cell infiltration, the tumor mutational burden (TMB), and tumor immune dysfunction and exclusion (TIDE) scores were calculated to investigate differences in the immune landscape. Finally, the expression of hub disulfidptosis-related lncRNAs was validated using qPCR. We established a novel signature comprised of eight lncRNAs that were associated with disulfidptosis (SPINT1-AS1, AL121944.1, AC131009.3, AC104088.3, AL035071.1, LINC00886, AL035587.2, and AC007743.1). Kaplan-Meier and receiver operating characteristic curves demonstrated the acceptable predictive potency of the model. The nomogram and C-index confirmed the strong correlation between the risk signature and clinical decision-making. Furthermore, immune cell infiltration analysis and ssGSEA revealed significantly different immune statuses among risk groups. TMB analysis revealed the link between the high-risk group and high TMB. It is worth noting that the cumulative effect of the patients belonging to the high-risk group and having elevated TMB led to decreased patient survival times. The high-risk group depicted greater TIDE scores in contrast with the low-risk group, indicating greater potential for immune escape. Finally, qPCR validated the hub disulfidptosis-related lncRNAs in cell lines. The established novel signature holds potential regarding the prognosis prediction of individuals with ccRCC as well as predicting their responses to immunotherapy.

References

Lim S, Wei J, Nguyen T, Shi H, Su W, Palacios G . Lipid signalling enforces functional specialization of T cells in tumours. Nature. 2021; 591(7849):306-311. PMC: 8168716. DOI: 10.1038/s41586-021-03235-6. View

Lv D, Xiang Y, Yang Q, Yao J, Dong Q . Long Non-Coding RNA TUG1 Promotes Cell Proliferation and Inhibits Cell Apoptosis, Autophagy in Clear Cell Renal Cell Carcinoma via MiR-31-5p/FLOT1 Axis. Onco Targets Ther. 2020; 13:5857-5868. PMC: 7311099. DOI: 10.2147/OTT.S254634. View

Liu C, Ma K, Zhang Y, He X, Song L, Chi M . Kidney diseases and long non-coding RNAs in the limelight. Front Physiol. 2022; 13:932693. PMC: 9589442. DOI: 10.3389/fphys.2022.932693. View

Lai J, Miao S, Ran L . Ferroptosis-associated lncRNA prognostic signature predicts prognosis and immune response in clear cell renal cell carcinoma. Sci Rep. 2023; 13(1):2114. PMC: 9902540. DOI: 10.1038/s41598-023-29305-5. View

Newman A, Liu C, Green M, Gentles A, Feng W, Xu Y . Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015; 12(5):453-7. PMC: 4739640. DOI: 10.1038/nmeth.3337. View

Zhou T, Lin K, Nie J, Pan B, He B, Pan Y . LncRNA SPINT1-AS1 promotes breast cancer proliferation and metastasis by sponging let-7 a/b/i-5p. Pathol Res Pract. 2020; 217:153268. DOI: 10.1016/j.prp.2020.153268. View

Zheng T, Liu Q, Xing F, Zeng C, Wang W . Disulfidptosis: a new form of programmed cell death. J Exp Clin Cancer Res. 2023; 42(1):137. PMC: 10230712. DOI: 10.1186/s13046-023-02712-2. View

Qi-Dong X, Yang X, Lu J, Liu C, Sun J, Li C . Development and Validation of a Nine-Redox-Related Long Noncoding RNA Signature in Renal Clear Cell Carcinoma. Oxid Med Cell Longev. 2021; 2020:6634247. PMC: 7781722. DOI: 10.1155/2020/6634247. View

Robert S, Buckingham S, Campbell S, Robel S, Holt K, Ogunrinu-Babarinde T . SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Sci Transl Med. 2015; 7(289):289ra86. PMC: 4503260. DOI: 10.1126/scitranslmed.aaa8103. View

10.

Shukla S, Wang C, Beiss V, Steinmetz N . Antibody Response against Cowpea Mosaic Viral Nanoparticles Improves Vaccine Efficacy in Ovarian Cancer. ACS Nano. 2020; 14(3):2994-3003. PMC: 8085886. DOI: 10.1021/acsnano.9b07865. View

11.

Dong X, Liao P, Liu X, Yang Z, Wang Y, Zhong W . Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer. Int J Mol Sci. 2023; 24(16). PMC: 10454603. DOI: 10.3390/ijms241612915. View

12.

Choueiri T, Heng D, Lee J, Cancel M, Verheijen R, Mellemgaard A . Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020; 6(8):1247-1255. PMC: 7260692. DOI: 10.1001/jamaoncol.2020.2218. View

13.

Rini B, Campbell S, Escudier B . Renal cell carcinoma. Lancet. 2009; 373(9669):1119-32. DOI: 10.1016/S0140-6736(09)60229-4. View

14.

Zhao L, Luo H, Dong X, Zeng Z, Zhang J, Yi Y . A novel necroptosis-related lncRNAs signature for survival prediction in clear cell renal cell carcinoma. Medicine (Baltimore). 2022; 101(39):e30621. PMC: 9524942. DOI: 10.1097/MD.0000000000030621. View

15.

Kanehisa M, Furumichi M, Sato Y, Kawashima M, Ishiguro-Watanabe M . KEGG for taxonomy-based analysis of pathways and genomes. Nucleic Acids Res. 2022; 51(D1):D587-D592. PMC: 9825424. DOI: 10.1093/nar/gkac963. View

16.

Shen F, Pan Y, Yang H, Li J, Zhao F, Su J . Decreased expression of SPINT1-AS1 and SPINT1 mRNA might be independent unfavorable prognostic indicators in esophageal squamous cell carcinoma. Onco Targets Ther. 2019; 12:4755-4763. PMC: 6591775. DOI: 10.2147/OTT.S206448. View

17.

Sui X, Hu N, Wang P, Wang Y, Meng C, Zhang Z . LncRNA SPINT1-AS1/miR-433-3p/E2F3 positive feedback loop promotes the KRAS-mutant colorectal cancer cell proliferation, migration and invasion. Pathol Res Pract. 2022; 239:154064. DOI: 10.1016/j.prp.2022.154064. View

18.

Lan L, Cao H, Chi W, Meng W, Zhao L, Cui W . Aberrant DNA hypermethylation-silenced LINC00886 gene accelerates malignant progression of laryngeal carcinoma. Pathol Res Pract. 2020; 216(4):152877. DOI: 10.1016/j.prp.2020.152877. View

19.

Liu L, Liu J, Lyu Q, Huang J, Chen Y, Feng C . Disulfidptosis-associated LncRNAs index predicts prognosis and chemotherapy drugs sensitivity in cervical cancer. Sci Rep. 2023; 13(1):12470. PMC: 10394072. DOI: 10.1038/s41598-023-39669-3. View

20.

Dong Z, Yang L, Lu J, Guo Y, Shen S, Liang J . Downregulation of LINC00886 facilitates epithelial-mesenchymal transition through SIRT7/ELF3/miR-144 pathway in esophageal squamous cell carcinoma. Clin Exp Metastasis. 2022; 39(4):661-677. DOI: 10.1007/s10585-022-10171-w. View