Abstract
To identify the prognostic biomarker of the competitive endogenous RNA (ceRNA) and explore the tumor infiltrating immune cells (TIICs) which might be the potential prognostic factors in lung adenocarcinoma. In addition, we also try to explain the crosstalk between the ceRNA and TIICs to explore the molecular mechanisms involved in lung adenocarcinoma. The transcriptome data of lung adenocarcinoma were obtained from The Cancer Genome Atlas (TCGA) database, and the hypergeometric correlation of the differently expressed miRNA-lncRNA and miRNA-mRNA were analyzed based on the starBase. In addition, the Kaplan–Meier survival and Cox regression model analysis were used to identify the prognostic ceRNA network and TIICs. Correlation analysis was performed to analysis the correlation between the ceRNA network and TIICs. In the differently expressed RNAs between tumor and normal tissue, a total of 190 miRNAs, 224 lncRNAs and 3024 mRNAs were detected, and the constructed ceRNA network contained 5 lncRNAs, 92 mRNAs and 10 miRNAs. Then, six prognostic RNAs (FKBP3, GPI, LOXL2, IL22RA1, GPR37, and has-miR-148a-3p) were viewed as the key members for constructing the prognostic prediction model in the ceRNA network, and three kinds of TIICs (Monocytes, Macrophages M1, activated mast cells) were identified to be significantly related with the prognosis in lung adenocarcinoma. Correlation analysis suggested that the FKBP3 was associated with Monocytes and Macrophages M1, and the GPI was obviously related with Monocytes and Macrophages M1. Besides, the LOXL2 was associated with Monocytes and Activated mast cells, and the IL22RA1 was significantly associated with Monocytes and Macrophages M1, while the GPR37 and Macrophages M1 was closely related. The constructed ceRNA network and identified Monocytes, Macrophages M1 and activated Mast cells are all prognostic factors for lung adenocarcinoma. Moreover, the crosstalk between the ceRNA network and TIICs might be a potential molecular mechanism involved.
Highlights
Lung cancer is one of the most frequently diagnosed malignancies worldwide, and it represents almost onequarter of all cancer d eaths[1]
Tumor infiltrating immune cells have been proved to be very important in the occurrence and development of tumors, and have shown the prognostic value of a variety of malignant tumors[26,27,28]
Previous studies have shown that the non-coding RNAs play a vital role in cancer occurrence and prognosis, and it has been generally recognized that the interactions between long non-coding RNAs (lncRNAs), miRNA and mRNA could regulate the expression levels of mRNAs and the affect the core protein signals, inducing the changes in physiological functions of cells[14]
Summary
Data collection and identification of differently expressed RNAs. We downloaded all the miRNA, lncRNA and mRNA expression profiles and relevant clinical data such as pathological factors, and the survival outcome of the lung adenocarcinoma cohort from The Cancer Genome Atlas (TCGA) (https://portal.gdc.cancer.gov/), including 497 cancer cases, 54 cases of adjacent normal tissues and 486 cases of relevant clinical data. We constructed a nomogram to predict the prognosis of lung adenocarcinoma patients and the calibration curves were utilised to access the accuracy. We performed Cox hazards regression analysis and Lasso regression analysis to identify the survival related immune cells, p-value < 0.05 were set as the cut-off. Correlation analysis was performed for each key gene in the ceRNA network and each survival related immune cell with the Pearson method
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