Identification of Prognostic MiRNAs Associated With Immune Cell Tumor Infiltration Predictive of Clinical Outcomes in Patients With Non-Small Cell Lung Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Jul 19

PMID 34277450

Citations 2

Authors

Yuepeng Zhang

Kai Mi

ZhiHeng Li

Lixia Qiang

Meiyu Lv

Yushan Wu

Ligong Yuan

Shoude Jin

Affiliations

Soon will be listed here.

Abstract

Background: A detailed means of prognostic stratification in patients with non-small cell lung cancer (NSCLC) is urgently needed to support individualized treatment plans. Recently, microRNAs (miRNAs) have been used as biomarkers due to their previously reported prognostic roles in cancer. This study aimed to construct an immune-related miRNA signature that effectively predicts NSCLC patient prognosis.

Methods: The miRNAs and mRNA expression and mutation data of NSCLC was obtained from The Cancer Genome Atlas (TCGA). Immune-associated miRNAs were identified using immune scores calculated by the ESTIMATE algorithm. LASSO-penalized multivariate survival models were using for development of a tumor immune-related miRNA signature (TIM-Sig), which was evaluated in several public cohorts from the Gene Expression Omnibus (GEO) and the CellMiner database. The miRTarBase was used for constructing the miRNA-target interactions.

Results: The TIM-Sig, including 10 immune-related miRNAs, was constructed and successfully predicted overall survival (OS) in the validation cohorts. TIM-Sig score negatively correlated with CD8+ T cell infiltration, IFN-γ expression, CYT activity, and tumor mutation burden. The correlation between TIM-Sig score and genomic mutation and cancer chemotherapeutics was also evaluated. A miRNA-target network of 10 miRNAs in TIM-Sig was constructed. Further analysis revealed that these target genes showed prognostic value in both lung squamous cell carcinoma and adenocarcinoma.

Conclusions: We concluded that the immune-related miRNAs demonstrated a potential value in clinical prognosis.

Citing Articles

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Identification of miRNA signature for predicting the prognostic biomarker of squamous cell lung carcinoma.

Liu H, Li T, Dong C, Lyu J PLoS One. 2022; 17(3):e0264645.

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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

Cai K, Bao X, Kong X, Jinag W, Mao M, Chu J . Hsa-miR-34c suppresses growth and invasion of human laryngeal carcinoma cells via targeting c-Met. Int J Mol Med. 2010; 25(4):565-71. DOI: 10.3892/ijmm_00000378. View

Devarakonda S, Rotolo F, Tsao M, Lanc I, Brambilla E, Masood A . Tumor Mutation Burden as a Biomarker in Resected Non-Small-Cell Lung Cancer. J Clin Oncol. 2018; 36(30):2995-3006. PMC: 6804865. DOI: 10.1200/JCO.2018.78.1963. View

Michlewski G, Caceres J . Post-transcriptional control of miRNA biogenesis. RNA. 2018; 25(1):1-16. PMC: 6298569. DOI: 10.1261/rna.068692.118. View

Siegel R, Miller K, Jemal A . Cancer statistics, 2019. CA Cancer J Clin. 2019; 69(1):7-34. DOI: 10.3322/caac.21551. View

Yu W, Ji N, Gu C, Sun Z, Wang Z, Chen Z . Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels. Chin Med J (Engl). 2019; 132(22):2705-2715. PMC: 6940098. DOI: 10.1097/CM9.0000000000000517. View

Dobrzanski M, Reome J, Hylind J, Rewers-Felkins K, Abulsamad K, Adams S . Ag-specific type 1 CD8 effector cells enhance methotrexate-mediated antitumor responses by modulating differentiated T cell localization, activation and chemokine production in established breast cancer. Clin Immunol. 2008; 128(2):205-18. DOI: 10.1016/j.clim.2008.03.518. View

De Simone M, Arrigoni A, Rossetti G, Gruarin P, Ranzani V, Politano C . Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells. Immunity. 2016; 45(5):1135-1147. PMC: 5119953. DOI: 10.1016/j.immuni.2016.10.021. View

Blower P, Verducci J, Lin S, Zhou J, Chung J, Dai Z . MicroRNA expression profiles for the NCI-60 cancer cell panel. Mol Cancer Ther. 2007; 6(5):1483-91. DOI: 10.1158/1535-7163.MCT-07-0009. View

10.

Terzic J, Seipel A, Dubuisson J, Tille J, Tsantoulis P, Addeo A . Sustained response to pembrolizumab without prior chemotherapy in high-grade serous ovarian carcinoma with mutation. Gynecol Oncol Rep. 2020; 33:100600. PMC: 7322246. DOI: 10.1016/j.gore.2020.100600. View

11.

Zhou C, Wei W, Ma J, Yang Y, Liang L, Zhang Y . Cancer-secreted exosomal miR-1468-5p promotes tumor immune escape via the immunosuppressive reprogramming of lymphatic vessels. Mol Ther. 2021; 29(4):1512-1528. PMC: 8058488. DOI: 10.1016/j.ymthe.2020.12.034. View

12.

Hanzelmann S, Castelo R, Guinney J . GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013; 14:7. PMC: 3618321. DOI: 10.1186/1471-2105-14-7. View

13.

Srivastava S, Gopal-Srivastava R . Biomarkers in cancer screening: a public health perspective. J Nutr. 2002; 132(8 Suppl):2471S-2475S. DOI: 10.1093/jn/132.8.2471S. View

14.

Danaher P, Warren S, Lu R, Samayoa J, Sullivan A, Pekker I . Pan-cancer adaptive immune resistance as defined by the Tumor Inflammation Signature (TIS): results from The Cancer Genome Atlas (TCGA). J Immunother Cancer. 2018; 6(1):63. PMC: 6013904. DOI: 10.1186/s40425-018-0367-1. View

15.

Deng J, Chen H, Zhou D, Zhang J, Chen Y, Liu Q . Comparative genomic analysis of esophageal squamous cell carcinoma between Asian and Caucasian patient populations. Nat Commun. 2017; 8(1):1533. PMC: 5688099. DOI: 10.1038/s41467-017-01730-x. View

16.

Dai G, Wang L, Wen Y, Ren X, Zuo S . Identification of key genes for predicting colorectal cancer prognosis by integrated bioinformatics analysis. Oncol Lett. 2020; 19(1):388-398. PMC: 6924121. DOI: 10.3892/ol.2019.11068. View

17.

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman D . IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017; 127(8):2930-2940. PMC: 5531419. DOI: 10.1172/JCI91190. View

18.

Mastroianni J, Stickel N, Andrlova H, Hanke K, Melchinger W, Duquesne S . miR-146a Controls Immune Response in the Melanoma Microenvironment. Cancer Res. 2018; 79(1):183-195. PMC: 6330089. DOI: 10.1158/0008-5472.CAN-18-1397. View

19.

He Y, Jiang Z, Chen C, Wang X . Classification of triple-negative breast cancers based on Immunogenomic profiling. J Exp Clin Cancer Res. 2018; 37(1):327. PMC: 6310928. DOI: 10.1186/s13046-018-1002-1. View

20.

Zhao J, Cheng M, Gai J, Zhang R, Du T, Li Q . SPOCK2 Serves as a Potential Prognostic Marker and Correlates With Immune Infiltration in Lung Adenocarcinoma. Front Genet. 2020; 11:588499. PMC: 7683796. DOI: 10.3389/fgene.2020.588499. View