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Comparative transcriptomic profiling between two radiologic phenotypes in lungs from patients with pulmonary disease caused by Mycobacterium avium complex

ABSTRACT: The incidence of Mycobacterium avium complex (MAC)-induced pulmonary disease (PD) has been increasing in South Korea, posing considerable challenges in treatment. Treatment guidelines recommend initiating therapy after serial computed tomography (CT) monitoring. While drug treatment often improves outcomes in patients with the nodular bronchiectatic (NB) form, those with the fibrocavitary (FC) form may continue to experience persistence despite treatment. Our objective was to classify type-specific and common genes based on radiological phenotypes (NB and FC) using RNA sequencing to analyze the cellular landscape of 11 NB sections, 10 FC sections, and 21 unaffected sections from 21 MAC-PD cases. Predictive in silico analysis indicated a significant role for genes related to B cell proliferation and regulation in both forms. Additionally, NB patients exhibited predominantly regulated antimicrobial immune responses, whereas FC patients showed enrichment in genes related to extracellular matrix structure. These target genes identified through genetic analysis could potentially serve as predictive biomarkers for type-specific biological processes and cellular pathways, necessitating further validation studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE270278 | GEO | 2024/07/01

REPOSITORIES: GEO

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Project description:Objectives and goals: The causes and molecular pathology of ovarian cancer are essentially unknown. However, it is generally understood that serous ovarian borderline tumors (SBOT) and well differentiated (WD) serous ovarian carcinomas (SC) have a similar tumorigenetic pathway, distinct from moderately (MD) and poorly differentiated (PD) SC. The aim of this study was to identify mRNAs differentially expressed between MD/PD SC, SBOT and superficial scrapings from normal ovaries (SNO),and to correlate these mRNAs with clinical parameters. Results: From the global gene expression analyses, thirty mRNAs differentially expressed between MD/PD SC, SBOT and SNO were selected and validated by RT-qPCR, verifying 21 mRNAs to be significantly differentially expressed (p<0.01). Of these, 13 mRNAs were differentially expressed in MD/PD SC compared with SNO (p<0.01) and were correlated with clinical parameters. VEGFA was significantly upregulated (FC=6.1, p=6.0x10-6), and correlated with progression-free survival (p=0.037). ZNF385B was significantly downregulated (FC=-130.5, p=1.2x10-7), and correlated with overall survival (p=0.03). An increased TPX2 (p=0.03) and FOXM1 (p=0.044) expression correlated with optimal normalization of serum CA125 after treatment. Furthermore, we present a common molecular pathway for MD/PD SC, including VEGFA, FOXM1, TPX2, BIRC5 and TOP2A, all significantly upregulated and interacting with TP53. Conclusions: We have identified 21 mRNAs differentially expressed (p<0.01) between MD/PD SC, SBOT and SNO. Thirteen were differentially expressed in MD/PD SC, including VEGFA and ZNF385B, correlating with survival, and FOXM1 and TPX2, correlating with normalization of serum CA125. By the use of oligonucleotid microarrays (Affymetrix U133 Plus 2.0 Arrays) differences in mRNA expression between eleven MD/PD SC, eight SBOT and four SNO samples were analyzed. Differentially expressed mRNAs were selected for validation by RT-qPCR in additional samples totaling 21 MD/PD SC, 13 SBOT and seven samples of SNO. Each mRNA was run in quadruple. The mRNAs differentially expressed in MD/PD SC compared with SNO were correlated with clinical parameters.

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Comparative transcriptomic profiling between two radiologic phenotypes in lungs from patients with pulmonary disease caused by Mycobacterium avium complex

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