Increased number of subclones in lung squamous cell carcinoma elicits overexpression of immune related genes

Song, Myung Jin; Lee, Sang Hoon; Kim, Eun Young; Chang, Yoon Soo

doi:10.21037/tlcr-19-589

Cited by 5 publications

(3 citation statements)

References 42 publications

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“…FDC-SP-deficient mice show significantly increased IgA levels in BALF ( Hou et al, 2014 ). In lung squamous cell carcinoma, the up-regulated FDCSP was strongly enriched for the positive regulation of immune processes and inflammatory responses ( Song et al, 2020 ). Interleukin-6 (IL-6) is the most increased gene in bronchial epithelium in the older adult group.…”

Section: Discussionmentioning

confidence: 99%

Transcriptomic profiles of age-related genes in female trachea and bronchus

Liu

Lu²,

Hu³

et al. 2023

Front. Genet.

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Background: Studies demonstrated that age-related cellular and functional changes of airway significantly contribute to the pathogenesis of many airway diseases. However, our understanding on the age-related molecular alterations of human airway remains inadequate.Methods: Airway (trachea and bronchus) brushing specimens were collected from 14 healthy, female non-smokers with ages ranging from 20 to 60 years. Bulk RNA sequencing was performed on all the specimens (n = 28). Airway cell types and their relative proportions were estimated using CIBERSORTx. The cell type proportions were compared between the younger (age 20–40) and elder group (age 40–60) in the trachea and bronchus respectively. The linear association between cell type proportion and age was assessed using the Pearson correlation coefficient. Differentially expressed genes (DEGs) between the two age groups were identified using DESeq2. Three kinds of enrichment analysis of the age-related DEGs were performed, including Gene ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and disease enrichment analysis.Results: Sixteen and thirteen cell types were separately identified in tracheal and bronchial brushings, with the airway epithelial cells (including suprabasal, submucosal gland (SMG) goblet, serous, secretory, multiciliated, cycling.basal, basal cells) accounting for 85.1% in the trachea and 92.5% in the bronchus. The lymphatic cell and NK cells had a higher abundance ratio in the trachea, compared with the bronchus. The proportion of basal cells was negatively related to age both in the trachea and bronchus. Thirty-one and fifty-two age-related DEGs (p < 0.1) were identified in the trachea and bronchus, respectively. Among them, five common DEGs (CXCL2, CXCL8, TCIM, P4HA3, AQP10) were identified. Pathway enrichment analysis showed both tracheal and bronchial age-related DEGs were primarily involved in immune regulatory signaling pathways (TNF, NF-kappa B, IL-17 et al.). Disease enrichment analysis suggested that tracheal age-related DEGs significantly related to asthmatic pulmonary eosinophilia, and chronic airflow obstruction et al., and that bronchial age-related DEGs were enriched in airflow obstruction, bronchiectasis, pulmonary emphysema, and low respiratory tract infection et al.Conclusion: We found the proportion of basal cells decreased with age in both the trachea and bronchus, suggesting a weakening of their self-renew ability with age. We identified transcriptomic signature genes associated with the early aging process of the human trachea and bronchus, and provided evidence to support that changes in their immune regulatory function may play critical roles in age-related airway diseases.

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Section: Discussionmentioning

confidence: 99%

Transcriptomic profiles of age-related genes in female trachea and bronchus

Liu

Lu²,

Hu³

et al. 2023

Front. Genet.

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“…15 Lung tissue transcriptome sequencing in the current study found 83 co-up-regulated DEGs in the comparison groups between TB and NonTB and between TB and ParaTB groups. FDCSP is related to immune cell activation and maturation and committing to regulating immune processes, 16 but its role in response to Mtb infection remains unclear. Among the 18 top immune-related co-up-regulated DEGs, six were associated with immune response in tuberculosis, including CXCL13, CR2, CD19, CCL19, CD79A, and TLR10 (Figure 4D).…”

Section: ■ Discussionmentioning

confidence: 99%

Microbiome Alteration in Lung Tissues of Tuberculosis Patients Revealed by Metagenomic Next-Generation Sequencing and Immune-Related Transcriptional Profile Identified by Transcriptome Sequencing

Liu,

Ji,

Fang

et al. 2023

ACS Infect. Dis.

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This study explored alterations in the respiratory microbiome and transcriptome after Mycobacterium tuberculosis infection in tuberculosis (TB) patients. Metagenomic next-generation sequencing (mNGS) was adopted to reveal the microbiome in lung tissues from 110 TB and 25 nontuberculous (NonTB) patients. Transcriptome sequencing was performed in TB tissues (n = 3), tissues adjacent to TB (ParaTB, n = 3), and NonTB tissues (n = 3) to analyze differentially expressed genes (DEGs) and functional pathways. The microbial β diversity (p = 0.01325) in TB patients differed from that in the NonTB group, with 17 microbial species distinctively distributed. Eighty-three co-up-regulated DEGs were identified in the TB versus NonTB and the TB versus ParaTB comparison groups, and six were associated with immune response to Mtb. These DEGs were significantly enriched in the signaling pathways such as immune response, NF-κB, and B cell receptor. Data in the lung tissue microbiome and transcriptome in TB patients offer a sufficient understanding of the pathogenesis of TB.

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“…Cancer is a highly diverse disease in nature. Recent research in cancer genomics has uncovered that even within a single tumor in a patient, there often exist multiple subclones [ 48 , 49 ]. Multiple subclones presumably accelerate the evolution of tumor resistance to treatment, serving as a potential source of resistant clones [ 50 ].…”

Section: Intratumoral Heterogeneitymentioning

confidence: 99%

Unraveling the Impact of Intratumoral Heterogeneity on EGFR Tyrosine Kinase Inhibitor Resistance in EGFR-Mutated NSCLC

Kobayashi

Tan

2023

IJMS

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The advent of tyrosine kinase inhibitors (TKIs) for treating epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) has been a game changer in lung cancer therapy. However, patients often develop resistance to the drugs within a few years. Despite numerous studies that have explored resistance mechanisms, particularly in regards to collateral signal pathway activation, the underlying biology of resistance remains largely unknown. This review focuses on the resistance mechanisms of EGFR-mutated NSCLC from the standpoint of intratumoral heterogeneity, as the biological mechanisms behind resistance are diverse and largely unclear. There exist various subclonal tumor populations in an individual tumor. For lung cancer patients, drug-tolerant persister (DTP) cell populations may have a pivotal role in accelerating the evolution of tumor resistance to treatment through neutral selection. Cancer cells undergo various changes to adapt to the new tumor microenvironment caused by drug exposure. DTP cells may play a crucial role in this adaptation and may be fundamental in mechanisms of resistance. Intratumoral heterogeneity may also be precipitated by DNA gains and losses through chromosomal instability, and the role of extrachromosomal DNA (ecDNA) may play an important role. Significantly, ecDNA can increase oncogene copy number alterations and enhance intratumoral heterogeneity more effectively than chromosomal instability. Additionally, advances in comprehensive genomic profiling have given us insights into various mutations and concurrent genetic alterations other than EGFR mutations, inducing primary resistance in the context of tumor heterogeneity. Understanding the mechanisms of resistance is clinically crucial since these molecular interlayers in cancer-resistance mechanisms may help to devise novel and individualized anticancer therapeutic approaches.

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Increased number of subclones in lung squamous cell carcinoma elicits overexpression of immune related genes

Cited by 5 publications

References 42 publications

Transcriptomic profiles of age-related genes in female trachea and bronchus

Transcriptomic profiles of age-related genes in female trachea and bronchus

Microbiome Alteration in Lung Tissues of Tuberculosis Patients Revealed by Metagenomic Next-Generation Sequencing and Immune-Related Transcriptional Profile Identified by Transcriptome Sequencing

Unraveling the Impact of Intratumoral Heterogeneity on EGFR Tyrosine Kinase Inhibitor Resistance in EGFR-Mutated NSCLC

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