An Efficient Five-lncRNA Signature for Lung Adenocarcinoma Prognosis, with AL606489.1 Showing Sexual Dimorphism

Overview

Journal Front Genet

Date 2022 Dec 19

PMID 36531243

Authors

Jiali Liang

Weifeng Jin

Huaping Xu

Affiliations

Soon will be listed here.

Abstract

Lung adenocarcinoma (LUAD) is a sex-biased and easily metastatic malignant disease. A signature based on 5 long non-coding RNAs (lncRNAs) has been established to promote the overall survival (OS) prediction effect on LUAD. The RNA expression profiles of LUAD patients were obtained from The Cancer Genome Atlas. OS-associated lncRNAs were identified based on the differential expression analysis between LUAD and normal samples followed by survival analysis, univariate and multivariate Cox proportional hazards regression analyses. OS-associated lncRNA with sex dimorphism was determined based on the analysis of expression between males and females. Functional enrichment analysis of the Gene Ontology (GO) terms and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed to explore the possible mechanisms of 5-lncRNA signatures. A 5-lncRNA signature (composed of AC068228.1, SATB2-AS1, LINC01843, AC026355.1, and AL606489.1) was found to be effective in predicting high-risk LUAD patients as well as applicable to female and male subgroups and <65-year and ≥65-year age subgroups. The forecasted effect of the 5-lncRNA signature was more efficient and stable than the TNM stage and other clinical risk factors (such as sex and age). Functional enrichment analysis revealed that the mRNA co-expressed with these five OS-related lncRNAs was associated with RNA regulation within the nucleus. AL606489.1 demonstrated a sexual dimorphism that may be associated with microtubule activity. Our 5-lncRNA signature could efficaciously predict the OS of LUAD patients. AL606489.1 demonstrated gender dimorphism, which provides a new direction for mechanistic studies on sexual dimorphism.

Citing Articles

Identification of anoikis-related long non-coding RNA signature as a novel prognostic model in lung adenocarcinoma.

Fang X, Wei M, Liu X, Lu L, Liu G Transl Cancer Res. 2024; 13(10):5458-5472.

PMID: 39525036 PMC: 11543027. DOI: 10.21037/tcr-24-264.

Non-Coding RNA as a Biomarker in Lung Cancer.

Suri C, Swarnkar S, Bhaskar L, Verma H Noncoding RNA. 2024; 10(5).

PMID: 39452836 PMC: 11514784. DOI: 10.3390/ncrna10050050.

An emerging link between lncRNAs and cancer sex dimorphism.

Naciri I, Andrade-Ludena M, Yang Y, Kong M, Sun S Hum Genet. 2023; 143(7):831-842.

PMID: 38095719 PMC: 11176266. DOI: 10.1007/s00439-023-02620-7.

References

Chen M, Liu X, Du J, Wang X, Xia L . Differentiated regulation of immune-response related genes between LUAD and LUSC subtypes of lung cancers. Oncotarget. 2016; 8(1):133-144. PMC: 5352059. DOI: 10.18632/oncotarget.13346. View

Moore K, Mery C, Jaklitsch M, Estocin A, Bueno R, Swanson S . Menopausal effects on presentation, treatment, and survival of women with non-small cell lung cancer. Ann Thorac Surg. 2003; 76(6):1789-95. DOI: 10.1016/s0003-4975(03)01024-5. View

Zhang Z, Qian W, Wang S, Ji D, Wang Q, Li J . Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma. Cell Physiol Biochem. 2018; 49(5):1778-1791. DOI: 10.1159/000493623. View

Lokhandwala P, Tseng L, Rodriguez E, Zheng G, Pallavajjalla A, Gocke C . Clinical mutational profiling and categorization of BRAF mutations in melanomas using next generation sequencing. BMC Cancer. 2019; 19(1):665. PMC: 6612071. DOI: 10.1186/s12885-019-5864-1. View

Snyder M, Gingeras T, Moore J, Weng Z, Gerstein M, Ren B . Perspectives on ENCODE. Nature. 2020; 583(7818):693-698. PMC: 7410827. DOI: 10.1038/s41586-020-2449-8. View

Tamang S, Acharya V, Roy D, Sharma R, Aryaa A, Sharma U . SNHG12: An LncRNA as a Potential Therapeutic Target and Biomarker for Human Cancer. Front Oncol. 2019; 9:901. PMC: 6759952. DOI: 10.3389/fonc.2019.00901. View

Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M . KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2020; 49(D1):D545-D551. PMC: 7779016. DOI: 10.1093/nar/gkaa970. View

Tomczak K, Czerwinska P, Wiznerowicz M . The Cancer Genome Atlas (TCGA): an immeasurable source of knowledge. Contemp Oncol (Pozn). 2015; 19(1A):A68-77. PMC: 4322527. DOI: 10.5114/wo.2014.47136. View

Song J, Sun Y, Cao H, Liu Z, Xi L, Dong C . A novel pyroptosis-related lncRNA signature for prognostic prediction in patients with lung adenocarcinoma. Bioengineered. 2021; 12(1):5932-5949. PMC: 8806662. DOI: 10.1080/21655979.2021.1972078. View

10.

Li X, Hemminki K . Inherited predisposition to early onset lung cancer according to histological type. Int J Cancer. 2004; 112(3):451-7. DOI: 10.1002/ijc.20436. View

11.

Yuan Y, Liu L, Chen H, Wang Y, Xu Y, Mao H . Comprehensive Characterization of Molecular Differences in Cancer between Male and Female Patients. Cancer Cell. 2016; 29(5):711-722. PMC: 4864951. DOI: 10.1016/j.ccell.2016.04.001. View

12.

Quinn J, Chang H . Unique features of long non-coding RNA biogenesis and function. Nat Rev Genet. 2015; 17(1):47-62. DOI: 10.1038/nrg.2015.10. View

13.

Musolf A, Simpson C, de Andrade M, Mandal D, Gaba C, Yang P . Parametric Linkage Analysis Identifies Five Novel Genome-Wide Significant Loci for Familial Lung Cancer. Hum Hered. 2017; 82(1-2):64-74. PMC: 8459795. DOI: 10.1159/000479028. View

14.

Guzzo R, Sevinc S, Salih M, Tuana B . A novel isoform of sarcolemmal membrane-associated protein (SLMAP) is a component of the microtubule organizing centre. J Cell Sci. 2004; 117(Pt 11):2271-81. DOI: 10.1242/jcs.01079. View

15.

Wu Y, Cheng Y, Zhou J, Lu S, Zhang Y, Zhao J . Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir Med. 2020; 8(11):1132-1143. DOI: 10.1016/S2213-2600(20)30154-5. View

16.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J . Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018; 379(21):2040-2051. DOI: 10.1056/NEJMoa1810865. View

17.

Jiang M, Ni J, Cui W, Wang B, Zhuo W . Emerging roles of lncRNA in cancer and therapeutic opportunities. Am J Cancer Res. 2019; 9(7):1354-1366. PMC: 6682721. View

18.

Couraud S, Zalcman G, Milleron B, Morin F, Souquet P . Lung cancer in never smokers--a review. Eur J Cancer. 2012; 48(9):1299-311. DOI: 10.1016/j.ejca.2012.03.007. View

19.

Yu J, Wu X, Huang K, Zhu M, Zhang X, Zhang Y . Bioinformatics identification of lncRNA biomarkers associated with the progression of esophageal squamous cell carcinoma. Mol Med Rep. 2019; 19(6):5309-5320. PMC: 6522958. DOI: 10.3892/mmr.2019.10213. View

20.

Collins F, Morgan M, Patrinos A . The Human Genome Project: lessons from large-scale biology. Science. 2003; 300(5617):286-90. DOI: 10.1126/science.1084564. View