Abstract
Accumulating evidence has demonstrated that gene alterations play a crucial role in LUAD development, progression, and prognosis. The present study aimed to identify the hub genes associated with LUAD. In the present study, we used TCGA database to screen the hub genes. Then, we validated the results by GEO datasets. Finally, we used cBioPortal, UALCAN, qRT-PCR, HPA database, TCGA database, and Kaplan–Meier plotter database to estimate the gene mutation, gene transcription, protein expression, clinical features of hub genes in patients with LUAD. A total of 5930 DEGs were screened out in TCGA database. Enrichment analysis revealed that DEGs were involved in the transcriptional misregulation in cancer, viral carcinogenesis, cAMP signaling pathway, calcium signaling pathway, and ECM–receptor interaction. The combining results of MCODE and CytoHubba showed that ADCY8, ADRB2, CALCA, GCG, GNGT1, and NPSR1 were hub genes. Then, we verified the above results by GSE118370, GSE136043, and GSE140797 datasets. Compared with normal lung tissues, the expression levels of ADCY8 and ADRB2 were lower in LUAD tissues, but the expression levels of CALCA, GCG, GNGT1, and NPSR1 were higher. In the prognosis analyses, the low expression of ADCY8 and ADRB2 and the high expression of CALCA, GCG, GNGT1, and NPSR1 were correlated with poor OS and poor PFS. The significant differences in the relationship of the expression of 6 hub genes and clinical features were observed. In conclusion, 6 hub genes will not only contribute to elucidating the pathogenesis of LUAD and may be potential therapeutic targets for LUAD.
Highlights
Lung cancer is a common and severe disease which ranks the top among cancers worldwide in terms of mortality for both men and women [1]
The results of the Gene ontology (GO) analysis indicated that in biological process terms, the up-regulated differentially expressed genes (DEGs) were mainly enriched in nucleosome assembly, telomere organization, and cellular protein metabolic process (Figure 2A, Table 3), down-regulated DEGs were significantly enriched in angiogenesis, receptor internalization, and cell surface receptor signaling pathway (Figure 2B, Table 3)
Up-regulated DEGs were mainly enriched in sequence-specific DNA binding, protein heterodimerization activity, and hormone activity (Figure 2A, Table 3), whereas down-regulated DEGs were mainly enriched in heparin binding, ion channel binding, and receptor activity (Figure 2B, Table 3)
Summary
Lung cancer is a common and severe disease which ranks the top among cancers worldwide in terms of mortality for both men and women [1]. In January 2021, the International Agency for Research on Cancer (IARC) published the latest cancer statistics in 2020, according to the statistics published after the investigation of incidence and mortality of 36 cancers in 185 countries, the new cases of lung cancer reached 2.2 million, ranking the second in the number of new cancer cases. About 1.8 million people die from lung cancer, the highest death rate from cancer. In China, the number of new cases and deaths of lung cancer is the highest among all cancers (820 thousand and 710 thousand respectively), accounting for 17.9% and 23.8% of all cancer incidence and mortality [2]. With the continuous development of molecular biology and the advocacy of precision medicine, the research and development of targets and targeted drugs in LUAD are becoming
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