mRNA expression profile as a potential biomarker for idiopathic and progressive pulmonary fibrosis: a pilot study

Interstitial lung diseases (ILD) include idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), both of which lead to severe respiratory failure within 3 – 5 years.

The aim of the study was to investigate the mRNA expression profile in blood mononuclear cells as a biomarker of IPF and PPF.

Methods. The 7-year prospective single-center study included patients (n = 110) with IPF (n = 16), PLF (n = 35), and nonprogressive ILD (n = 59). The pilot analysis of mRNA expression included patients (n = 24) with progressive PLF (n = 16) and IPF (n = 8) and a control group (n = 20). Since proinflammatory cytokines (IL-1A, IL-6, IL-8), interferon regulatory factors (IRF5, IRF7), KIF2C, CIITA, TYMS, HJURP, CDKN1A, UBE2C, BIRC5 proteins and pulmonary surfactants (SpA, SpB) are involved in immunity regulation, the expression level of 14 mRNA in blood mononuclear cells of patients with progressive pulmonary fibrosis was analyzed.

Results. Similar pathological patterns of mRNA expression of 9 genes (IL6, IRF5, IRF7, TYMS, HJURP, UBE2C, BIRC5, SpA, SpB) were revealed in patients with PLF and IPF compared to the controls. Expression of 5 genes (KIF2C, CIITA, CDKN1A, IL6, IL8) was significantly reduced. ROC analysis demonstrated that IL6 mRNA expression in peripheral blood mononuclear cells (AUC = 0.700) can serve as an informative noninvasive biomarker for the adverse course of ILD, including IPF and PPF.

Conclusion. A statistically significant decrease in KIF2C, CDKN1A, CIITA, IL6, and IL8 mRNA expression was detected in patients with progressive ILD. IL6 mRNA levels have acceptable prognostic significance (AUC = 0.700) and can be used as a noninvasive biomarker for progressive fibrosing lung diseases.

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