Abstract
BackgroundEither chronic or acute exposure to dust particles may lead to pneumoconiosis and lung cancer, and lung cancer mortality among patients diagnosed with pneumoconiosis is increasing. Utilizing genome-wide sequencing technology, this study aimed to identify methods to decrease the number of patients with pneumoconiosis who die from lung cancer.MethodsOne hundred fifty-four subjects were recruited, including 54 pneumoconiosis patients and 100 healthy controls. Exosomes were isolated from the venous blood of every subject. Distinctive miRNAs were identified using high throughput sequencing technology, and bioinformatics analysis predicted target genes involved in lung cancer as well as their corresponding biological functions. Moreover, cross-cancer alterations of genes related to lung cancer were investigated, and survival analysis was performed using 2437 samples with an average follow-up period of 49 months.ResultsLet-7a-5p was revealed to be downregulated by 21.67% in pneumoconiosis. Out of the 683 let-7a-5p target genes identified from bioinformatics analysis, four genes related to five signaling pathways were confirmed to be involved in lung cancer development. Alterations in these four target genes were then explored in 4105 lung cancer patients, and BCL2L1 and IGF1R were demonstrated to be aberrantly expressed. Survival analysis further revealed that high expression of BCL2L1 corresponded to reduced survival of lung cancer patients (HR (95%CI) = 1.75(1.33~2.30)), while patient survival time was unaffected by expression of IGF1R (HR (95%CI) = 1.15 (0.98~1.36)).ConclusionsIn patients with lung adenocarcinoma, simultaneous downregulation of exosomal let-7a-5p and elevated expression of BCL2L1 are useful as predictive biomarkers for poor survival.
Highlights
Either chronic or acute exposure to dust particles may lead to pneumoconiosis and lung cancer, and lung cancer mortality among patients diagnosed with pneumoconiosis is increasing
Cross-cancer alteration of let-7a-5p target genes To investigate alterations of four target genes of let-7a-5p in lung cancer, we explored their expression in lung cancer (lung adenocarcinoma (LA) and lung squamous carcinoma (LSC)) using TCGA database
Relative expression levels of exosomal let-7a-5p in venous blood from pneumoconiosis patients was decreased by 21.67% (0.47 ± 0.24 vs. 0.60 ± 0.24, t = 3.11, P = 0.002) (Fig. 1b), consistent with high throughput sequencing results shown in our previous study [8], suggesting that exosomal let-7a-5p may be involved in the development of pneumoconiosis
Summary
Either chronic or acute exposure to dust particles may lead to pneumoconiosis and lung cancer, and lung cancer mortality among patients diagnosed with pneumoconiosis is increasing. Utilizing genome-wide sequencing technology, this study aimed to identify methods to decrease the number of patients with pneumoconiosis who die from lung cancer. Researchers have proposed that patients suffering from pneumoconiosis are likely at high risk for developing lung cancer. Exosomal let-7a-5p and let-7i-5p were found to be associated with nanoparticle phagocytosis. Both of these factors simultaneously target WASL and VASP inducing inflammatory responses in lung tissue [8]. Let-7a was shown to be differentially expressed in different subtypes of non-small cell lung cancer [9,10,11]. Let-7 families may be useful as specific biomarkers for distinguishing different subtypes of lung cancer
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