Copyright (c) 2023 Yanli Luo, Sheng Zhang, Huilin Xie, Qiaofeng Su, Shuang He, Zhen Lei
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.Prognosis and immunotherapy significances of a cancer-associated fibroblasts-related gene signature in lung adenocarcinoma
Corresponding Author(s) : Zhen Lei
Cellular and Molecular Biology,
Vol. 69 No. 14: Cancer molecular biology: Diagnosis and treatment
Abstract
Cells associated with cancer (CAFs) contribute significantly to the stroma of a tumor microenvironment (TME), which is related to the occurrence, treatment, and prognosis of lung adenocarcinoma (LUAD). Therefore, this study investigated the function of CAF-associated genes in the microenvironment of LUAD. The Cancer Genome Atlas (TCGA) database was used to download RNA-seq data from the TCGA Lung Adenocarcinoma cohort (TCGA-LUAD). The GSE68465 dataset, as the external validation set, was from the Gene Expression Omnibus (GEO) database. Besides, CAF-associated genes were sourced from the GeneCards and Molecular Signatures Database (MsigDB). For LUAD, differentially expressed CAF-related genes were selected from overlapping CAF and LUAD patient and control samples. Next, LASSO and Univariate Cox analyses were used to construct the risk model. Additionally, an analysis of Cox regression was used to construct a nomogram. Next, the immune infiltration in malignant tumour tissues was compared between high- and low-risk groups using Estimation of STromal and Immune cells in MAlignant Tumours (ESTIMATE) tissues and Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT). The sensitivity differences of immunotherapy between the two risk groups were estimated by Tumor Immune Dysfunction and Exclusion (TIDE), and compared by rank-sum test. Finally, the model genes were detected by fluorescent real-time quantitative polymerase chain reaction (qRT-PCR). A total of 57 DE-CAFGs were acquired, and 9 of them (SHCBP1, CCNA2, AKAP12, CCNB1, GALNT3, SCGB1A1, CPS1, CDC6, and CXCL13) were selected as prognostic biomarkers. The Cox independent prognosis revealed the RiskScore and Stage were the two LUAD independent prognosis factors Moreover, 11 types of immune cells (memory B cells, resting natural killer cells (NK cells), Eosinophils, Macrophages M0, CD4 memory resting T cells, CD4 memory activated T cells, resting Mast cells, naive B cells, T cells regulatory (Tregs), neutrophils, and plasma cell), and 18 human leukocyte antigen (HLA) genes were different with the two risk groups. Lastly, the TIDE analysis showed differences between the two risk groups for TIDE, T cell dysfunction, and T cell exclusion, PD-L1 treatment scores. Lastly, Both LUAD and normal samples expressed the 9 model genes differently. A CAF-related prognostic model was constructed, which may have potential immunotherapy guiding significance for LUAD patients.
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