Could Periostin Be a Viable Biomarker for IPF?

Background

Periostin is a matricellular protein that attaches to matrix proteins and cellular receptors to modulate cell function.¹ It is important in the maintenance and development of bones, teeth, and the heart, and is expressed in tumors and metastatic cancer cells.^2,3 In addition, periostin is expressed in various pathophysiological states of fibrosis, including the healing process in myocardial infarction.^3,4

Accumulating evidence appears to support periostin as a biomarker for IPF. In 2011, Okamoto et al first noted that in patients with IPF, serum periostin levels were significantly higher than in control subjects.⁵ Additionally, serum periostin levels correlated significantly with declines of vital capacity (VC) and diffusing capacity for carbon monoxide.⁵ Later, Naik et al found that serum periostin levels could predict disease progression at 48 weeks in patients with IPF.¹ Taking the research further, Tajiri, Okamoto, Fujimoto, Johkoh, et al attempted to determine whether serum periostin levels could be correlated with long-term survival in patients with IPF.⁴

What They Did

The authors identified 29 patients with IPF at their center for whom long-term data were available.⁴ Study subjects were observed for at least 2 years and for up to 5 years, after the first observation day. Serum periostin levels, overall survival (OS), time to event (TTE) (defined as a complicating acute exacerbation or a ≥10% decline from baseline in VC), and the extent of abnormal findings on high-resolution computed tomography (HRCT scores) were analyzed. The mean observation period was 1035±663 days (range, 112–1800 days).

What They Found

During the follow-up period, 16 of the 29 subjects died due to causes other than malignant disease.⁴ Two patients died of cancer (bladder and lung) and were censored. Higher serum periostin level (≥106 ng/mL) was found to be a significant predictor of shortened OS in log-rank test (P=0.0072) (Figure 1). Similarly, a higher serum periostin level was found to be a significant predictor of shortened TTE (P=0.0011). Further, from baseline to 6 months, higher levels of serum periostin were significantly correlated with a change in honeycombing score on HRCT (P=0.045). Other HRCT scores were not correlated with levels of serum periostin.

Figure 1.
Kaplan–Meier survival curves for overall survival. Used with permission from Tajiri M, et al. Respir Investig. 2015;53:73-81

What It Means

In IPF, there is a need for biomarkers that can be obtained by noninvasive means. This study shows for the first time that serum levels of periostin can predict shortened OS and TTE in patients with IPF.⁴ If the findings of this small study are confirmed in larger populations, serum periostin levels may ultimately be a viable biomarker for predicting long-term outcomes in patients with IPF.

Link to Abstract: http://www.ncbi.nlm.nih.gov/pubmed/?term=25745852

References

1. Naik PK, Bozyk PD, Bentley JK, et al. Periostin promotes fibrosis and predicts progression in patients with idiopathic pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol. 2012;303:L1046-L1056.
2. Horiuchi K, Amizuka N, Takeshita S, et al. Identification and characterization of a novel protein, periostin, with restricted expression to periosteum and periodontal ligament and increased expression by transforming growth factor beta. J Bone Miner Res. 1999;14:1239-1249.
3. Oka T, Xu J, Kaiser RA, et al. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling. Circ Res. 2007;101:313-321.
4. Tajiri M, Okamoto M, Fujimoto K, et al. Serum level of periostin can predict long-term outcome of idiopathic pulmonary fibrosis. Respir Investig. 2015;53:73-81.
5. Okamoto M, Hoshino T, Kitasato Y, et al. Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias. Eur Respir J. 2011;37:1119-1127.