Abstract

This study aimed to establish a prognostic risk model for lung adenocarcinoma (LUAD). We firstly divided 535 LUAD samples in TCGA-LUAD into high-, medium-, and low-immune infiltration groups by consensus clustering analysis according to immunological competence assessment by single-sample gene set enrichment analysis (ssGSEA). Profile of long non-coding RNAs (lncRNAs) in normal samples and LUAD samples in TCGA was used for a differential expression analysis in the high- and low-immune infiltration groups. A total of 1,570 immune-related differential lncRNAs in LUAD were obtained by intersecting the above results. Afterward, univariate COX regression analysis and multivariate stepwise COX regression analysis were conducted to screen prognosis-related lncRNAs, and an eight-immune-related-lncRNA prognostic signature was finally acquired (AL365181.2, AC012213.4, DRAIC, MRGPRG-AS1, AP002478.1, AC092168.2, FAM30A, and LINC02412). Kaplan–Meier analysis and ROC analysis indicated that the eight-lncRNA-based model was accurate to predict the prognosis of LUAD patients. Simultaneously, univariate COX regression analysis and multivariate COX regression analysis were undertaken on clinical features and risk scores. It was illustrated that the risk score was a prognostic factor independent from clinical features. Moreover, immune data of LUAD in the TIMER database were analyzed. The eight-immune-related-lncRNA prognostic signature was related to the infiltration of B cells, CD4+ T cells, and dendritic cells. GSEA enrichment analysis revealed significant differences in high- and low-risk groups in pathways like pentose phosphate pathway, ubiquitin mediated proteolysis, and P53 signaling pathway. This study helps to treat LUAD patients and explore molecules related to LUAD immune infiltration to deeply understand the specific mechanism.

Highlights

  • Lung cancer has the highest morbidity and mortality among all cancers in the world (The Lancet, 2018)

  • Since many clinical traits are related to prognosis of cancer, we focused on detecting the independence of the eightimmune-related-long non-coding RNAs (lncRNAs) prognostic signature

  • The CD274 gene, which plays an important role in the immune escape of cancer cells, encodes programmed death ligand-1 (PD-L1)

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Summary

Introduction

Lung cancer has the highest morbidity and mortality among all cancers in the world (The Lancet, 2018). More than 50% of lung cancer patients have tumor metastasis when diagnosed, with a 5-year survival rate of only 5% (Siegel et al, 2020). Lung adenocarcinoma (LUAD) accounts for 40% of all lung cancers, with a 5-year survival rate of only 15%, since patients. LncRNA Prognostic for Lung Adenocarcinoma are diagnosed when the cancer has been locally advanced and developed metastasis (Imielinski et al, 2012). Malignant phenotype of cancers is both influenced by cell characteristics itself and tumor microenvironment (TME) (Catalano et al, 2013). Accumulating studies have suggested the correlation between the infiltration level of immune cells in TME and clinical outcomes. A study on colon carcinoma elaborated the impact of T cell infiltration on cancer recurrence rate (Mlecnik et al, 2011). Tumor immune infiltration is crucial in cancer progression

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