Identification of a Apoptosis-related LncRNA Signature to Improve Prognosis Prediction and Immunotherapy Response in Lung Adenocarcinoma Patients

Overview

Journal Front Genet

Date 2022 Sep 29

PMID 36171881

Authors

Ting Luo

Shiqun Yu

Jin Ouyang

Fanfan Zeng

Liyun Gao

Shaoxin Huang

Xin Wang

Affiliations

Soon will be listed here.

Abstract

Apoptosis is closely associated with the development of various cancers, including lung adenocarcinoma (LUAD). However, the prognostic value of apoptosis-related lncRNAs (ApoRLs) in LUAD has not been fully elucidated. In the present study, we screened 2, 960 ApoRLs by constructing a co-expression network of mRNAs-lncRNAs associated with apoptosis, and identified 421 ApoRLs that were differentially expressed between LUAD samples and normal lung samples. Sixteen differentially expressed apoptosis-related lncRNAs (DE-ApoRLs) with prognostic relevance to LUAD patients were screened using univariate Cox regression analysis. An apoptosis-related lncRNA signature (ApoRLSig ) containing 10 ApoRLs was constructed by applying the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression method, and all LUAD patients in the TCGA cohort were divided into high or low risk groups. Moreover, patients in the high-risk group had a worse prognosis ( < 0.05). When analyzed in conjunction with clinical features, we found ApoRLSig to be an independent predictor of LUAD patients and established a prognostic nomogram combining ApoRLSig and clinical features. Gene set enrichment analysis (GSEA) revealed that ApoRLSig is involved in many malignancy-associated immunomodulatory pathways. In addition, there were significant differences in the immune microenvironment and immune cells between the high-risk and low-risk groups. Further analysis revealed that the expression levels of most immune checkpoint genes (ICGs) were higher in the high-risk group, which suggested that the immunotherapy effect was better in the high-risk group than in the low-risk group. And we found that the high-risk group was also better than the low-risk group in terms of chemotherapy effect. In conclusion, we successfully constructed an ApoRLSig which could predict the prognosis of LUAD patients and provide a novel strategy for the antitumor treatment of LUAD patients.

Citing Articles

Identification and verification of a PANoptosis-related long noncoding ribonucleic acid signature for predicting the clinical outcomes and immune landscape in lung adenocarcinoma.

Bao L, Ye Y, Zhang X, Xu X, Wang W, Jiang B Heliyon. 2024; 10(8):e29869.

PMID: 38681588 PMC: 11053219. DOI: 10.1016/j.heliyon.2024.e29869.

Xu Q, Wang C, Yin G Front Genet. 2023; 13:993509.

PMID: 36685822 PMC: 9846524. DOI: 10.3389/fgene.2022.993509.

References

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

Chen P, Zeng Z, Wang J, Cao W, Song C, Lei S . Long noncoding RNA LINC00857 promotes pancreatic cancer proliferation and metastasis by regulating the miR-130b/RHOA axis. Cell Death Discov. 2022; 8(1):198. PMC: 9008000. DOI: 10.1038/s41420-022-01008-2. View

Chen Y, Xu J, Wu X, Yao H, Yan Z, Guo T . CD147 regulates antitumor CD8 T-cell responses to facilitate tumor-immune escape. Cell Mol Immunol. 2020; 18(8):1995-2009. PMC: 8322173. DOI: 10.1038/s41423-020-00570-y. View

Zheng J, Zhao Z, Wan J, Guo M, Wang Y, Yang Z . N-6 methylation-related lncRNA is potential signature in lung adenocarcinoma and influences tumor microenvironment. J Clin Lab Anal. 2021; 35(11):e23951. PMC: 8605119. DOI: 10.1002/jcla.23951. View

Liu C, Wang Y, Wang C, Feng P, Ko H, Liu Y . Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14⁻/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol. 2009; 136(1):35-45. DOI: 10.1007/s00432-009-0634-0. View

Feng P, Lee K, Chang Y, Chan Y, Kuo L, Lin T . CD14(+)S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am J Respir Crit Care Med. 2012; 186(10):1025-36. PMC: 4132576. DOI: 10.1164/rccm.201204-0636OC. View

DArcy M . Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019; 43(6):582-592. DOI: 10.1002/cbin.11137. View

Knight S, Crosbie P, Balata H, Chudziak J, Hussell T, Dive C . Progress and prospects of early detection in lung cancer. Open Biol. 2017; 7(9). PMC: 5627048. DOI: 10.1098/rsob.170070. View

Biswas S, Sica A, Lewis C . Plasticity of macrophage function during tumor progression: regulation by distinct molecular mechanisms. J Immunol. 2008; 180(4):2011-7. DOI: 10.4049/jimmunol.180.4.2011. View

10.

Zou X, He R, Zhang Z, Yan Y . Apoptosis-Related Signature Predicts Prognosis and Immune Microenvironment Infiltration in Lung Adenocarcinoma. Front Genet. 2022; 13:818403. PMC: 9094710. DOI: 10.3389/fgene.2022.818403. View

11.

Becker Y . Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy--a review. Virus Genes. 2006; 33(2):235-52. DOI: 10.1007/s11262-006-0064-x. View

12.

Huang H, Yang C, Zhang Q, Zhuo T, Li X, Li N . Long non-coding RNA FAM83A antisense RNA 1 (lncRNA FAM83A-AS1) targets microRNA-141-3p to regulate lung adenocarcinoma cell proliferation, migration, invasion, and epithelial-mesenchymal transition progression. Bioengineered. 2022; 13(3):4964-4977. PMC: 8973779. DOI: 10.1080/21655979.2022.2037871. View

13.

Su W, Wang L, Zhao H, Hu S, Zhou Y, Guo C . Interacting with YBX1 to Regulate Apoptosis and Autophagy via MET and Phosphor-AMPKa Signaling. Mol Ther Nucleic Acids. 2020; 22:1164-1175. PMC: 7701017. DOI: 10.1016/j.omtn.2020.10.025. View

14.

Xiu D, Liu G, Yu S, Li L, Zhao G, Liu L . Long non-coding RNA LINC00968 attenuates drug resistance of breast cancer cells through inhibiting the Wnt2/β-catenin signaling pathway by regulating WNT2. J Exp Clin Cancer Res. 2019; 38(1):94. PMC: 6385430. DOI: 10.1186/s13046-019-1100-8. View

15.

Huang A, Zhang B, Wang B, Zhang F, Fan K, Guo Y . Increased CD14(+)HLA-DR (-/low) myeloid-derived suppressor cells correlate with extrathoracic metastasis and poor response to chemotherapy in non-small cell lung cancer patients. Cancer Immunol Immunother. 2013; 62(9):1439-51. PMC: 11028777. DOI: 10.1007/s00262-013-1450-6. View

16.

Wang X, Li G, Luo Q, Xie J, Gan C . Integrated TCGA analysis implicates lncRNA CTB-193M12.5 as a prognostic factor in lung adenocarcinoma. Cancer Cell Int. 2018; 18:27. PMC: 5824544. DOI: 10.1186/s12935-018-0513-3. View

17.

Liu G, Pei F, Yang F, Li L, Amin A, Liu S . Role of Autophagy and Apoptosis in Non-Small-Cell Lung Cancer. Int J Mol Sci. 2017; 18(2). PMC: 5343902. DOI: 10.3390/ijms18020367. View

18.

Melief C . Cancer immunotherapy by dendritic cells. Immunity. 2008; 29(3):372-83. DOI: 10.1016/j.immuni.2008.08.004. View

19.

Saito M, Suzuki H, Kono K, Takenoshita S, Kohno T . Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy. Surg Today. 2017; 48(1):1-8. DOI: 10.1007/s00595-017-1497-7. View

20.

Johnstone R, Ruefli A, Lowe S . Apoptosis: a link between cancer genetics and chemotherapy. Cell. 2002; 108(2):153-64. DOI: 10.1016/s0092-8674(02)00625-6. View