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. 2024 Jan 5;24(1):41.
doi: 10.1186/s12885-023-11785-3.

Identification of key genes in chronic intermittent hypoxia-induced lung cancer progression based on transcriptome sequencing

Li-Da Chen #  1 , Li Lin #  1 , Ji-Zhi Chen  2 , Yang Song  3 , Wei-Liang Zhang  1 , Huang-Yu Li  1 , Jia-Min Luo  1 , Xiao-Bin Zhang  4   5
Affiliations

Identification of key genes in chronic intermittent hypoxia-induced lung cancer progression based on transcriptome sequencing

Li-Da Chen et al. BMC Cancer. .

Abstract

Background: Obstructive sleep apnea (OSA) is associated with increased risk of lung cancer mortality. Nevertheless, little is known about the underlying molecular mechanisms. This research aimed to investigate differentially expressed genes (DEGs) and explore their function in Lewis lung carcinoma (LLC)-bearing mice exposed to chronic intermittent hypoxia (CIH) by transcriptome sequencing.

Methods: Lung cancer tissues in LLC-bearing mice exposed to CIH or normoxia were subjected for transcriptome sequencing to examine DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to explore the function of DEGs. To evaluate the prognostic value of DEGs, the Kaplan-Meier survival analysis in combination with Cox proportional hazard model were applied based on The Cancer Genome Atlas.

Results: A total of 388 genes with 207 up-regulated and 181 down-regulated genes were differentially expressed between the CIH and normoxia control groups. Bioinformatics analysis revealed that the DEGs were related to various signaling pathways such as chemokine signaling pathway, IL-17 signaling pathway, TGF-β signaling pathway, transcriptional misregulation in cancer, natural killer cell mediated cytotoxicity, PPAR signaling pathway. In addition, the DEGs including APOL1, ETFB, KLK8, PPP1R3G, PRL, SPTA1, PLA2G3, PCP4L1, NINJ2, MIR186, and KLRG1 were proven to be significantly correlated with poorer overall survival in lung adenocarcinoma.

Conclusions: CIH caused a significant change of gene expression profiling in LLC-bearing mice. The DEGs were found to be involved in various physiological and pathological processes and correlated with poorer prognosis in lung cancer.

Keywords: Chronic intermittent hypoxia; Lung cancer; Obstructive sleep apnea; RNA sequencing; Transcriptome.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
DEGs between CIH group and NC group. A Bar graph for the number of up- and down-regulated DEGs. B Heat map generated by hierarchical clustering of DEGs in CIH group and NC group, red color representing increased expressed genes and blue color for decreased expressed genes. C Volcano plot of DEGs between CIH group and NC group, red dots representing the up-regulated DEGs, blue dots representing the down-regulated DEGs
Fig. 2
Fig. 2
GO analyses of DEGs. A GO terms for the up-regulated DEGs. B GO terms for the down-regulated DEGs. Y-axis represents GO terms, X-axis represents the p value
Fig. 3
Fig. 3
KEGG pathway analyses of DEGs. A Top 20 pathways associated with up-regulated DEGs (B) Top 20 pathways related to down-regulated DEGs. The size of the dot represents the number of genes, the color of the dot represents risk factor, Y-axis shows pathway name, X-axis shows the p value
Fig. 4
Fig. 4
The overall survivals of lung adenocarcinoma patients with high or low gene expression. A-F The up-regulated DEGs. (G-K) The low-regulated DEGs
Fig. 5
Fig. 5
DEGs validated by qRT-PCR. A The relative expression levels of 6 DGEs by qRT-PCR analysis (n = 3). B The expression pattern of DEGs in both qRT-PCR and RNA-seq. *p < 0.05; **p < 0.01
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