Analysis and Validation of the Prognosis Ability of the M7GRelated MiRNAs in Lung Adenocarcinoma

Overview

Journal Asian Pac J Cancer Prev

Specialty Oncology

Date 2023 Apr 28

PMID 37116150

Authors

Xiaowen Qiu

Yongting Chen

Xingzhuang Zhu

Zheng Gong

Fengyuan Yu

Pengfei Zhang

Yipeng Song

Hongwei Li

Affiliations

Soon will be listed here.

Abstract

Background: N7-methylguanosine (m7G) modification plays a crucial role in the development and progression of lung cancers. MicroRNAs (miRNAs) are closely involved in programmed cell death and the mechanism of tumor growth. The m7G-associated miRNAs genes in lung adenocarcinoma (LUAD), and their prognosis prediction ability of LUAD, however, had not been investigated.

Methods: The RNA transcriptomes, clinical indices, and immune scores of LUAD patients were searched and downloaded from The Cancer Genome Atlas (TCGA) and the ESTIMATE database. The miRNAs targeting METTL1 and WDR4 were extracted from the TargetScan database. Differentially expressed m7G-related miRNAs were identified and their prediction power of LUAD prognosis was systematically investigated.

Results: Among 40 the differentially expressed m7G-related miRNAs in LUAD, five (hsa-miR-31-5p, hsa-miR-5571-3p, hsa-miR-4697-3p, hsa-miR-6858-5p, and hsa-miR-873-3p) demonstrate significant predictive value for prognosis. The risk score constructed by these five miRNAs was an independent prognostic factor (univariate Cox regression results: hazard ratio (HR) = 1.6619, 95% confidential interval (CI) = 1.2103-2.2819, p = 0.0017; multivariate Cox regression results: HR = 1.6004, 95% CI = 1.1633-2.2017, p = 0.0039). The survival curves showed that patients with high-risk scores had a poor prognosis. Calibration curves indicated good predictability in a nomogram constructed combining the miRNA and the clinical indices of age, sex, chemotherapy, radiotherapy, stage, and risk score. GO and KEGG analysis of the overlapping genes showed that the prognostic miRNAs were closely associated with the neuropeptide signaling pathway. Besides, the immune infiltration analysis showed that the expression of the AMPD1 gene was strongly associated with immune cells and immunology functions in LUAD.

Conclusion: This study identified DE m7G-related miRNAs and demonstrated their prediction ability in the prognosis of LUAD patients. The risk signature based on these miRNAs demonstrates high accuracy in predicting the prognosis of LUAD patients.

Citing Articles

A signature of five 7-methylguanosine-related genes is a prognostic marker for lung squamous cell carcinoma.

Liu W, Wang Y, Ulivi P, Tavolari S, Rizvi S, Capobianco E J Thorac Dis. 2023; 15(11):6265-6278.

PMID: 38090319 PMC: 10713324. DOI: 10.21037/jtd-23-1504.

References

Szekely B, Bossuyt V, Li X, Wali V, Patwardhan G, Frederick C . Immunological differences between primary and metastatic breast cancer. Ann Oncol. 2018; 29(11):2232-2239. DOI: 10.1093/annonc/mdy399. View

Li D, Yang M, Shi S, Du Y, Wang H, Zhou Y . TM4SF5-CTD-2354A18.1-miR-4697-3P may play a key role in the pathogenesis of gastric cancer. Bratisl Lek Listy. 2015; 116(10):608-15. DOI: 10.4149/bll_2015_118. View

Catacchio I, Scattone A, Silvestris N, Mangia A . Immune Prophets of Lung Cancer: The Prognostic and Predictive Landscape of Cellular and Molecular Immune Markers. Transl Oncol. 2018; 11(3):825-835. PMC: 6050352. DOI: 10.1016/j.tranon.2018.04.006. View

Lin S, Liu Q, Lelyveld V, Choe J, Szostak J, Gregory R . Mettl1/Wdr4-Mediated mG tRNA Methylome Is Required for Normal mRNA Translation and Embryonic Stem Cell Self-Renewal and Differentiation. Mol Cell. 2018; 71(2):244-255.e5. PMC: 6086580. DOI: 10.1016/j.molcel.2018.06.001. View

Lu Z, He Q, Liang J, Li W, Su Q, Chen Z . miR-31-5p Is a Potential Circulating Biomarker and Therapeutic Target for Oral Cancer. Mol Ther Nucleic Acids. 2019; 16:471-480. PMC: 6495075. DOI: 10.1016/j.omtn.2019.03.012. View

Wang R, Wu Y, Huang W, Chen W . MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells. Oncol Res. 2017; 26(1):145-155. PMC: 7844674. DOI: 10.3727/096504017X14902261600566. View

Wu Z, Zhong Y, Zhou T, Xiao H . miRNA biomarkers for predicting overall survival outcomes for head and neck squamous cell carcinoma. Genomics. 2020; 113(1 Pt 1):135-141. DOI: 10.1016/j.ygeno.2020.12.002. View

Xie M, Lv Y, Liu Z, Zhang J, Liang C, Liao X . Identification and validation of a four-miRNA (miRNA-21-5p, miRNA-9-5p, miR-149-5p, and miRNA-30b-5p) prognosis signature in clear cell renal cell carcinoma. Cancer Manag Res. 2018; 10:5759-5766. PMC: 6245347. DOI: 10.2147/CMAR.S187109. View

Siegel R, Miller K, Jemal A . Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1):7-30. DOI: 10.3322/caac.21387. View

10.

Xu G, Shao G, Pan Q, Sun L, Zheng D, Li M . MicroRNA-9 regulates non-small cell lung cancer cell invasion and migration by targeting eukaryotic translation initiation factor 5A2. Am J Transl Res. 2017; 9(2):478-488. PMC: 5340683. View

11.

Deng Y, Xia J, Xu Y . Circular RNA circTP63 enhances estrogen receptor-positive breast cancer progression and malignant behaviors through the miR-873-3p/FOXM1 axis. Anticancer Drugs. 2020; 32(1):44-52. DOI: 10.1097/CAD.0000000000001010. View

12.

Lv Y, Duanmu J, Fu X, Li T, Jiang Q . Identifying a new microRNA signature as a prognostic biomarker in colon cancer. PLoS One. 2020; 15(2):e0228575. PMC: 7015317. DOI: 10.1371/journal.pone.0228575. View

13.

Ma J, Han H, Huang Y, Yang C, Zheng S, Cai T . METTL1/WDR4-mediated mG tRNA modifications and mG codon usage promote mRNA translation and lung cancer progression. Mol Ther. 2021; 29(12):3422-3435. PMC: 8636169. DOI: 10.1016/j.ymthe.2021.08.005. View

14.

He L, Qu L, Wei L, Chen Y, Suo J . Reduction of miR‑132‑3p contributes to gastric cancer proliferation by targeting MUC13. Mol Med Rep. 2017; 15(5):3055-3061. PMC: 5428394. DOI: 10.3892/mmr.2017.6347. View

15.

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

16.

Mi B, Li Q, Li T, Liu G, Sai J . High miR-31-5p expression promotes colon adenocarcinoma progression by targeting TNS1. Aging (Albany NY). 2020; 12(8):7480-7490. PMC: 7202535. DOI: 10.18632/aging.103096. View

17.

Hanahan D, Coussens L . Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012; 21(3):309-22. DOI: 10.1016/j.ccr.2012.02.022. View

18.

Tang J, Ma W, Zeng Q, Tan J, Cao K, Luo L . Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer. Dis Markers. 2020; 2019:3815952. PMC: 6954483. DOI: 10.1155/2019/3815952. View

19.

El Bezawy R, Cominetti D, Fenderico N, Zuco V, Beretta G, Dugo M . miR-875-5p counteracts epithelial-to-mesenchymal transition and enhances radiation response in prostate cancer through repression of the EGFR-ZEB1 axis. Cancer Lett. 2017; 395:53-62. DOI: 10.1016/j.canlet.2017.02.033. View

20.

Shi Y, Fan S, Wu M, Zuo Z, Li X, Jiang L . YTHDF1 links hypoxia adaptation and non-small cell lung cancer progression. Nat Commun. 2019; 10(1):4892. PMC: 6814821. DOI: 10.1038/s41467-019-12801-6. View