Role of hemoglobin alpha and hemoglobin beta in non‐small‐cell lung cancer based on bioinformatics analysis

Abstract

The differentially expressed genes (DEGs) were identified and screened differentially in non‐small‐cell lung cancer (NSCLC) using information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases, and the correlation of DEGs in protein interaction, function, and pathway enrichment were analyzed to search for new biomarkers and potential therapeutic targets for NSCLC. Protein–protein interaction network (PPI) analysis showed that CDK1 and GNGT1 were the most significantly upregulated hub nodes, while FPR2 was the most significantly downregulated. Gene Ontology enrichment analysis showed that upregulated DEGs were significantly enriched in protein heterodimerization activity and other functions, while downregulated DEGs were enriched in functions such as heparin‐binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulation of DEGs were significantly associated with neuroactive ligand‐receptor interaction pathways, while downregulation of DEGs were significantly associated with malaria pathways. According to the analysis results, we identified hemoglobin alpha (HBA) and hemoglobin beta (HBB) as the genes of interest for further study. Through tissue level and cell level experiments, we found that the expressions of HBA and HBB in NSCLC tissues were significantly lower than those in paracancerous tissues, and downregulation of HBA and HBB could significantly affect the proliferation ability of NSCLC cells. In addition, we also found that changes in HBA and HBB may affect NSCLC cells through the p38/MAPK pathway and JNK pathway, and ultimately affect the occurrence and development of NSCLC.

HBB as a Novel Biomarker for the Diagnosis and Monitoring of Lung Cancer Regulates Cell Proliferation via ERK1/2 Pathway

“… 23 These results indicated that HBB had an inhibitory effect on the occurrence and development of tumors. In our study, we found HBB expressions were down-regulated in both lung cancer tissues and plasma samples, this was consistent with the report by Kang et al 9 The expression HBB had a high diagnostic value in lung cancer by ROC curve analysis. Moreover, the combination of HBB and CEA was more significant than HBB or CEA alone in the diagnosis of lung cancer.…”

“…It had been found that HBB could suppress the proliferation of nonsmall-cell lung carcinoma through P38/MAPK and JNK pathways. 9 The objective of our research is to verify the potential of HBB as a molecular indicator for diagnosing and prognosticating lung cancer, as well as its role in modulating cellular proliferation.…”

Identification of key genes and biological pathways in chronic obstructive pulmonary disease using bioinformatics and next generation sequencing data analysis

“…It includes 43 COPD and 39 normal control samples, we found 956 DEGs (including 478 up regulated genes and 478 down regulated genes). HBB (hemoglobin subunit beta) [52], HLA-DQA1 [53], EGR1 [54], ATF3 [55], XIST (X inactive specific transcript) [56], CD163 [57] and S100A8 [58] plays a crucial role in the pathogenesis of lung cancer and considered a promising target for pharmacological based therapies. HBB (hemoglobin subunit beta) [59], HBA1 [60], HLA-DQA1 [61], EGR1 [62], ATF3 [63], XIST (X inactive specific transcript) [64], S100A12 [65], CD163 [66] and S100A8 [67] are closely related to the progression of diabetes mellitus.…”

Deep learning-based survival prediction using DNA methylation-derived 3D genomic information

“…Interestingly, all DMR genes we found to be related to the gas transport were the genes encoding subunits of hemoglobin, which transports oxygen. One of these genes, HBB, is reported to be abnormally expressed in many cancer types [46][47][48] . This result suggests the possibility that genes frequently altered in cancer, although not directly related to the developmental process, can also be regulated by open sea CpG probes.…”