Chest
Original ResearchPulmonary Vascular DiseaseGene Expression Profiling in the Lungs of Patients With Pulmonary Hypertension Associated With Pulmonary Fibrosis
Section snippets
Subjects
One hundred sixteen fresh-frozen lung tissue specimens were obtained from the recipient organs of PF patients undergoing LTx. For the development analysis, the explanted lung specimens from 84 consecutive patients with PF (January 2001 to February 2007) were used (development set). For the validation analysis, lung specimens from 32 consecutive PF patients (March 2007 to October 2008) were analyzed (validation set) (Table 1). Systolic and diastolic pulmonary artery pressures (PAPs) were
SAM Identified Gene Signatures Based on PAP
The prevalence of PH (mPAP > 25 mm Hg) was 62% in the development set and 56% in the validation set (Table 1). There were no significant differences between the severe PH and the NoPH groups in terms of demographics and PFTs, with the exception of diffusing capacity of the lung for carbon monoxide (Dlco) (Table 2). Representative histologic slides from a patient with severe PH are showed in Figure 2.
SAM identified 222 differentially expressed genes between the severe PH and NoPH groups. One
Discussion
To our knowledge, this is the first study to compare the gene expression profiles of patients with PF and with and without APH. The high numerosity of the population studied allowed us to compare the “phenotypic extremes” in terms of PAP and to demonstrate that severe PH and NoPH groups of patients with PF exhibit distinct gene expression profiles. A mPAP ≥ 40 mm Hg is commonly considered as severe APH in patients with ILD,12, 22, 23 whereas an mPAP of 20 to 24 mm Hg may indicate borderline PH,
Conclusions
In conclusion, the gene expression signatures based on mPAP identified by microarray analysis in this study not only provide a rationale for the development of APH in a significant subset of patients with PF, but also identify an analytic framework to determine therapeutic targets for the treatment of APH. If validated at the protein level, gene expression signatures could potentially be used for patient selection in future trials for patients with PF.
Acknowledgments
Author contributions: Dr Mura takes responsibility for the integrity of the work as a whole, from inception to published article.
Dr Mura: contributed to the study concept and design, analysis and interpretation of the data, and drafting of the manuscript and review for important intellectual content.
Dr Anraku: contributed to the analysis and interpretation of the data and drafting of the manuscript and review for important intellectual content.
Ms Yun: contributed to the analysis and
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2021, Biochimica et Biophysica Acta - Molecular Basis of DiseaseCitation Excerpt :Even though transcriptomics studies are very diverse, if we were to group the results into a common subject, many of them would involve differences in the function of genes related to the immune system and inflammation. Some examples are Toll-like receptors [58,59], T-cell receptors [58], B-cell receptors [60], interleukin and chemokines [61–66], and TGF-beta signaling [67]. The lack of consistency between all these studies may be mainly due to the significant variation in the types of samples analyzed (e.g., lung tissue, PAEC, PASMC, and peripheral blood mononuclear cells (PBMC)), and the great diversity of pulmonary hypertension types, including idiopathic, hereditary or secondary to another pathology (mainly systemic sclerosis), whose pathogenesis mechanisms can be highly variable.
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2018, Cellular ImmunologyCitation Excerpt :To our knowledge, this is the first investigation in which such comparisons have been performed. Previous transcriptomic profiling studies compared lung tissues from patients with IPF against tissues from healthy controls [5–17], but without differentiating macroscopically normal-appearing and scarred tissues. We also included healthy control tissues (HC) in our analyses, and performed complex, three-way comparisons (HC vs IPFn, HC vs IPFs, IPFn vs IPFs).
Funding/Support: This study was supported by the Roche Multi Organ Transplant Academic Enrichment Fund and by the Lawson Scholarship.
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