An Effective Hypoxia-Related Long Non-Coding RNA Assessment Model for Prognosis of Lung Adenocarcinoma

Yuanshuai Li1,2, Xiaofang Sun1,2
1Department of Obstetrics and Gynecology, China
2Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, China

Tóm tắt

Background: Lung adenocarcinoma (LUAD) represents one of the highest incidence rates worldwide. Hypoxia is a significant biomarker associated with poor prognosis of LUAD. However, there are no definitive markers of hypoxia-related long non-coding RNAs (lncRNAs) in LUAD.Methods: From The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB), we acquired the expression of hypoxia-related lncRNAs and corresponding clinical information of LUAD patients. The hypoxia-related prognostic model was constructed by univariable COX regression analysis, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analysis. To assess the performance of the model, the Kaplan–Meier (KM) survival and receiver operating characteristic (ROC) curve analyses were performed.Results: We found seven lncRNAs, AC022613.1, AC026355.1, GSEC, LINC00941, NKILA, HSPC324, and MYO16-AS1, as biomarkers of the potential hypoxia-related prognostic signature. In the low-risk group, patients had a better overall survival (OS). In addition, the results of ROC analysis indicated that the risk score predicted LUAD prognosis exactly. Furthermore, combining the expression of lncRNAs with clinical features, two predictive nomograms were constructed, which could accurately predict OS and had high clinical application value.Conclusion: In summary, the seven-lncRNA prognostic signature related to hypoxia might be useful in predicting clinical outcomes and provided new molecular targets for the research of LUAD patients.

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Tài liệu tham khảo

Aponte-López, 2020, Mast Cells in the Tumor Microenvironment, Adv. Exp. Med. Biol., 1273, 159, 10.1007/978-3-030-49270-0_9

Ashrafizadeh, 2021, Dual Relationship between Long Non-coding RNAs and STAT3 Signaling in Different Cancers: New Insight to Proliferation and Metastasis, Life Sci., 270, 119006, 10.1016/j.lfs.2020.119006

Bhan, 2017, Long Noncoding RNA and Cancer: A New Paradigm, Cancer Res., 77, 3965, 10.1158/0008-5472.CAN-16-2634

Carter, 2018, Revisions to the TNM Staging of Lung Cancer: Rationale, Significance, and Clinical Application, Radiographics, 38, 374, 10.1148/rg.2018170081

Chang, 2021, Novel lncRNA LINC00941 Promotes Proliferation and Invasion of Colon Cancer through Activation of MYC, Ott, 1173, 10.2147/OTT.S293519

Chang, 2016, Hypoxia-regulated lncRNAs in Cancer, Gene, 575, 1, 10.1016/j.gene.2015.08.049

Chen, 2021, Characterization of Tumor Microenvironment in Lung Adenocarcinoma Identifies Immune Signatures to Predict Clinical Outcomes and Therapeutic Responses, Front. Oncol., 11, 581030, 10.3389/fonc.2021.581030

Chen, 2020, Construction of a Nomogram Based on a Hypoxia-Related lncRNA Signature to Improve the Prediction of Gastric Cancer Prognosis, Front. Genet., 11, 570325, 10.3389/fgene.2020.570325

Choudhry, 2016, The Tumour Hypoxia Induced Non-coding Transcriptome, Mol. Aspects Med., 35, 10.1016/j.mam.2016.01.003

Dehghani, 2012, Prognostic Significance of T Cell Subsets in Peripheral Blood of B Cell Non-hodgkin's Lymphoma Patients, Med. Oncol., 29, 2364, 10.1007/s12032-012-0176-1

Fang, 2021, LINC00941 Promotes Proliferation and Metastasis of Pancreatic Adenocarcinoma by Competitively Binding miR-873-3p and Thus Upregulates ATXN2, Eur. Rev. Med. Pharmacol. Sci., 25, 1861, 10.26355/eurrev_202102_25081

Fang, 2016, Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer, Genomics, Proteomics & Bioinformatics, 14, 42, 10.1016/j.gpb.2015.09.006

Guo, 2020, Identification of Three Autophagy-Related Long Non-coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature, Front. Oncol., 10, 603864, 10.3389/fonc.2020.603864

Hirsch, 2017, Lung Cancer: Current Therapies and New Targeted Treatments, The Lancet, 389, 299, 10.1016/S0140-6736(16)30958-8

Jafarzadeh, 2020, LncRNA HSPC324 Plays Role in Lung Development and Tumorigenesis, Genomics, 112, 2615, 10.1016/j.ygeno.2020.02.012

Jiang, 2021, Identification and Validation of an Autophagy-Related Long Non-coding RNA Signature as a Prognostic Biomarker for Patients with Lung Adenocarcinoma, J. Thorac. Dis., 13, 720, 10.21037/jtd-20-2803

Jin, 2020, Identification of a Seven-lncRNA Immune Risk Signature and Construction of a Predictive Nomogram for Lung Adenocarcinoma, Biomed. Res. Int., 2020, 1, 10.1155/2020/7929132

Kumar, 2014, Hypoxia-inducible Factors in Regulation of Immune Responses in Tumour Microenvironment, Immunology, 143, 512, 10.1111/imm.12380

Labiano, 2015, Immune Response Regulation in the Tumor Microenvironment by Hypoxia, Semin. Oncol., 42, 378, 10.1053/j.seminoncol.2015.02.009

Lemjabbar-Alaoui, 2015, Lung Cancer: Biology and Treatment Options, Biochim. Biophys. Acta (Bba) - Rev. Cancer, 1856, 189, 10.1016/j.bbcan.2015.08.002

Li, 2021, BioSeq-BLM: a Platform for Analyzing DNA, RNA and Protein Sequences Based on Biological Language Models, Nucleic Acids Res., 49, e129, 10.1093/nar/gkab829

Li, 2014, starBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and Protein-RNA Interaction Networks from Large-Scale CLIP-Seq Data, Nucl. Acids Res., 42, D92, 10.1093/nar/gkt1248

Li, 2020, A Seven Immune-Related lncRNAs Model to Increase the Predicted Value of Lung Adenocarcinoma, Front. Oncol., 10, 560779, 10.3389/fonc.2020.560779

Li, 2016, Regulation of lncRNA and its Role in Cancer Metastasis, Oncol. Res., 23, 205, 10.3727/096504016X14549667334007

Li, 2021, Construction of a Prognostic Immune-Related LncRNA Risk Model for Lung Adenocarcinoma, Front. Cel Dev. Biol., 9, 648806, 10.3389/fcell.2021.648806

Liu, 2019, BioSeq-Analysis2.0: an Updated Platform for Analyzing DNA, RNA and Protein Sequences at Sequence Level and Residue Level Based on Machine Learning Approaches, Nucleic Acids Res., 47, e127, 10.1093/nar/gkz740

Liu, 2020, LncRNA GSEC Promotes the Proliferation, Migration and Invasion by Sponging miR-588/EIF5A2 axis in Osteosarcoma, Biochem. Biophysical Res. Commun., 532, 300, 10.1016/j.bbrc.2020.08.056

Ma, 2021, Hypoxia Activated Long Non-coding RNA HABON Regulates the Growth and Proliferation of Hepatocarcinoma Cells by Binding to and Antagonizing HIF-1 Alpha, RNA Biol., 18, 1791, 10.1080/15476286.2020.1871215

Ma, 2021, An Effective N6-Methyladenosine-Related Long Non-coding RNA Prognostic Signature for Predicting the Prognosis of Patients with Bladder Cancer, BMC Cancer, 21, 1256, 10.1186/s12885-021-08981-4

Odintsov, 2021, Novel Preclinical Patient-Derived Lung Cancer Models Reveal Inhibition of HER3 and MTOR Signaling as Therapeutic Strategies for NRG1 Fusion-Positive Cancers, J. Thorac. Oncol., 16, 1149, 10.1016/j.jtho.2021.03.013

Peng, 2018, Glycolysis Gatekeeper PDK1 Reprograms Breast Cancer Stem Cells under Hypoxia, Oncogene, 37, 1062, 10.1038/onc.2017.368

Peng, 2017, LncRNA-mediated Regulation of Cell Signaling in Cancer, Oncogene, 36, 5661, 10.1038/onc.2017.184

Rami-Porta, 2017, Lung Cancer - Major Changes in the American Joint Committee on Cancer Eighth Edition Cancer Staging Manual, CA: A Cancer J. Clinicians, 67, 138, 10.3322/caac.21390

Sanchez-Martinez, 2018, Expansion of Allogeneic NK Cells with Efficient Antibody-dependent Cell Cytotoxicity against Multiple Tumors, Theranostics, 8, 3856, 10.7150/thno.25149

Shi, 2016, Somatic Genomics and Clinical Features of Lung Adenocarcinoma: A Retrospective Study, Plos Med., 13, e1002162, 10.1371/journal.pmed.1002162

Shi, 2021, Identification and Validation of Hypoxia-Derived Gene Signatures to Predict Clinical Outcomes and Therapeutic Responses in Stage I Lung Adenocarcinoma Patients, Theranostics, 11, 5061, 10.7150/thno.56202

Tao, 2021, Targeting Hypoxic Tumor Microenvironment in Pancreatic Cancer, J. Hematol. Oncol., 14, 14, 10.1186/s13045-020-01030-w

Wang, 2021, Long Noncoding RNA LINC00941 Promotes Pancreatic Cancer Progression by Competitively Binding miR-335-5p to Regulate ROCK1-Mediated LIMK1/Cofilin-1 Signaling, Cell Death Dis, 12, 36, 10.1038/s41419-020-03316-w

Wang, 2020, Identification of a Glycolysis-Related LncRNA Signature to Predict Survival in Diffuse Glioma Patients, Front. Oncol., 10, 597877, 10.3389/fonc.2020.597877

Wu, 2021, A Novel Autophagy‐related lncRNA Survival Model for Lung Adenocarcinoma, J. Cel Mol Med, 25, 5681, 10.1111/jcmm.16582

You, 2021, Identification of a RNA-Seq Based Prognostic Signature with Seven Immune-Related lncRNAs for Lung Adenocarcinoma, Clin. Lab., 67, 663, 10.7754/Clin.Lab.2020.200663

Zhang, 2021, An Effective Hypoxia-Related Long Non-coding RNAs Assessment Model for Prognosis of Clear Cell Renal Carcinoma, Front. Oncol., 11, 616722, 10.3389/fonc.2021.616722

Zhang, 2021, Dissecting the Role of N6-Methylandenosine-Related Long Non-coding RNAs Signature in Prognosis and Immune Microenvironment of Breast Cancer, Front. Cel Dev. Biol., 9, 711859, 10.3389/fcell.2021.711859

Zhang, 2021, Construction of a Novel Signature and Prediction of the Immune Landscape in Soft Tissue Sarcomas Based on N6-Methylandenosine-Related LncRNAs, Front. Mol. Biosci., 8, 715764, 10.3389/fmolb.2021.715764

Zhou, 2021, Construction of an Immune-Related Six-lncRNA Signature to Predict the Outcomes, Immune Cell Infiltration, and Immunotherapy Response in Patients with Hepatocellular Carcinoma, Front. Oncol., 11, 661758, 10.3389/fonc.2021.661758

Zhu, 2018, Integrated Analysis of a Competing Endogenous RNA Network Reveals Key lncRNAs as Potential Prognostic Biomarkers for Human Bladder Cancer, Medicine (Baltimore), 97, e11887, 10.1097/MD.0000000000011887