A Novel Nomogram Model for Lung Adenocarcinoma Subtypes Based on RNA-modification Regulatory Genes

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Jul 18

PMID 39022104

Authors

Xiao Chen

Meng-Yu Zhang

Xiu-Li Ji

Rui Li

Qing-Xiang Wang

Yi-Qing Qu

Affiliations

Soon will be listed here.

Abstract

Background: In non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD) is the most common subtype. RNA modification has become the frontier and hotspot of current tumor research.

Results: In this study, 109 genes that regulate RNA modifications were identified according to The Cancer Genome Atlas (TCGA). A differential gene expression analysis identified 46 differentially expressed RNA modification regulatory genes (DERRGs). LUAD samples were stratified into two distinct clusters based on the expression of these DERRGs. A significant correlation was observed between these clusters and patient survival rates, as well as clinical features. Furthermore, a four-DERRG signature (EIF3B, HNRNPC, IGF2BP1, and METTL3) developed using LASSO regression. According to the calculated risk scores from this signature, LUAD patients were categorized into high-risk and low-risk groups. Patients in the low-risk group exhibited a more favorable prognosis. A prognostic nomogram was crafted, integrating the four-DERRGs signature with clinical parameters. The nomogram was revealed that OS, age, clinical stage, immune cell infiltration, and immune checkpoint molecule expression were significantly linked to the OS of LUAD. GSEA analysis found that the DERRGs were primarily regulated immune pathways.

Conclusions: This study developed four DERRGs signatures and formulated a nomogram model for precise prognosis estimation in LUAD patients. The study's insights are instrumental for advancing diagnosis, prognosis, and therapeutic strategies for LUAD.

References

Zhu X, Chen L, Liu L, Niu X . EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies. Front Oncol. 2019; 9:1044. PMC: 6798878. DOI: 10.3389/fonc.2019.01044. View

Teng P, Liang Y, Yarmishyn A, Hsiao Y, Lin T, Lin T . RNA Modifications and Epigenetics in Modulation of Lung Cancer and Pulmonary Diseases. Int J Mol Sci. 2021; 22(19). PMC: 8508636. DOI: 10.3390/ijms221910592. View

Boccaletto P, Machnicka M, Purta E, Piatkowski P, Baginski B, Wirecki T . MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2017; 46(D1):D303-D307. PMC: 5753262. DOI: 10.1093/nar/gkx1030. View

Dolcetta-Capuzzo A, Villa V, Albarello L, Franchi G, Gemma M, Scavini M . Gastroenteric neuroendocrine neoplasms classification: comparison of prognostic models. Cancer. 2012; 119(1):36-44. DOI: 10.1002/cncr.27716. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Chan T, Yarchoan M, Jaffee E, Swanton C, Quezada S, Stenzinger A . Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2018; 30(1):44-56. PMC: 6336005. DOI: 10.1093/annonc/mdy495. View

Ning J, Wang F, Bu J, Zhu K, Liu W . Down-regulated m6A reader FTO destabilizes PHF1 that triggers enhanced stemness capacity and tumor progression in lung adenocarcinoma. Cell Death Discov. 2022; 8(1):354. PMC: 9363432. DOI: 10.1038/s41420-022-01125-y. View

Li X, Feng Z, Wang R, Hu J, He X, Shen Z . Expression Status and Prognostic Value of mA RNA Methylation Regulators in Lung Adenocarcinoma. Life (Basel). 2021; 11(7). PMC: 8306618. DOI: 10.3390/life11070619. View

Zheng P, Li N, Zhan X . Ovarian cancer subtypes based on the regulatory genes of RNA modifications: Novel prediction model of prognosis. Front Endocrinol (Lausanne). 2022; 13:972341. PMC: 9760687. DOI: 10.3389/fendo.2022.972341. View

10.

Safra M, Sas-Chen A, Nir R, Winkler R, Nachshon A, Bar-Yaacov D . The m1A landscape on cytosolic and mitochondrial mRNA at single-base resolution. Nature. 2017; 551(7679):251-255. DOI: 10.1038/nature24456. View

11.

Xu X, Cui J, Wang H, Ma L, Zhang X, Guo W . IGF2BP3 is an essential N-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells. Mater Today Bio. 2022; 17:100503. PMC: 9707255. DOI: 10.1016/j.mtbio.2022.100503. View

12.

Nombela P, Miguel-Lopez B, Blanco S . The role of mA, mC and Ψ RNA modifications in cancer: Novel therapeutic opportunities. Mol Cancer. 2021; 20(1):18. PMC: 7812662. DOI: 10.1186/s12943-020-01263-w. View

13.

Zhang L, Peng H, Jiang L . Oncogenic Role of Heterogeneous Nuclear Ribonucleoprotein C in Multiple Cancer Types, with a Particular Focus on Lung Adenocarcinoma, Using a Pan-Cancer Analysis and Cell Line Experiments. J Environ Pathol Toxicol Oncol. 2022; 41(3):77-93. DOI: 10.1615/JEnvironPatholToxicolOncol.2022042822. View

14.

Chen Y, Tang L, Huang W, Zhang Y, Abisola F, Li L . Identification and validation of a novel cuproptosis-related signature as a prognostic model for lung adenocarcinoma. Front Endocrinol (Lausanne). 2022; 13:963220. PMC: 9637654. DOI: 10.3389/fendo.2022.963220. View

15.

Wu H, Xu H, Huang S, Tang Y, Tang J, Zhou H . mA-binding protein IGF2BP1 promotes the malignant phenotypes of lung adenocarcinoma. Front Oncol. 2022; 12:989817. PMC: 9554348. DOI: 10.3389/fonc.2022.989817. View

16.

Khan A, Huang H, Zhao Y, Li H, Pan R, Wang S . WBSCR22 and TRMT112 synergistically suppress cell proliferation, invasion and tumorigenesis in pancreatic cancer via transcriptional regulation of ISG15. Int J Oncol. 2022; 60(3). PMC: 8857931. DOI: 10.3892/ijo.2022.5314. View

17.

Heagerty P, Zheng Y . Survival model predictive accuracy and ROC curves. Biometrics. 2005; 61(1):92-105. DOI: 10.1111/j.0006-341X.2005.030814.x. View

18.

Li R, Li J, Liu T, Huo C, Yao J, Ji X . Prognostic Value of Genomic Instability of mA-Related lncRNAs in Lung Adenocarcinoma. Front Cell Dev Biol. 2022; 10:707405. PMC: 8928224. DOI: 10.3389/fcell.2022.707405. View

19.

Bohnsack K, Hobartner C, Bohnsack M . Eukaryotic 5-methylcytosine (m⁵C) RNA Methyltransferases: Mechanisms, Cellular Functions, and Links to Disease. Genes (Basel). 2019; 10(2). PMC: 6409601. DOI: 10.3390/genes10020102. View

20.

Zheng Q, Yu X, Zhang Q, He Y, Guo W . Genetic characteristics and prognostic implications of m1A regulators in pancreatic cancer. Biosci Rep. 2021; 41(4). PMC: 8035622. DOI: 10.1042/BSR20210337. View