CA 19-9 serum levels in patients with end-stage idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs): Correlation with functional decline

Abstract

Idiopathic pulmonary fibrosis presents a progressive and heterogeneous functional decline. CA 19-9 has been proposed as biomarker to predict disease course, but its role remains unclear. We assessed CA 19-9 levels and clinical data in end-stage ILD patients (48 IPF and 20 non-IPF ILD) evaluated for lung transplant, to correlate these levels with functional decline. Patients were categorized based on their rate of functional decline as slow (n = 20; ΔFVC%pred ≤ 10%/year) or rapid progressors (n = 28; ΔFVC%pred ≥ 10%/year). Nearly half of the entire patients (n = 32; 47%) had CA 19-9 levels ≥37kU/L. CA 19-9 levels in IPF were not different from non-IPF ILD populations, however, the latter group had a median CA 19-9 level above the normal cut-off value of 37 KU/l (60 [17–247] kU/L). Among IPF patients, CA 19-9 was higher in slow than in rapid progressors with a trend toward significance (33vs17kU/L; p = 0.055). In the whole population, CA19-9 levels were inversely related with ΔFVC/year (r = −0.261; p = 0.03), this correlation remained in IPF patients, particularly in rapid progressors (r = −0.51; p = 0.005), but not in non. Moreover, IPF rapid progressors with normal CA 19-9 levels showed the greater ΔFVC/year compared to those with abnormal CA 19-9 (0.95 vs. 0.65 L/year; p = 0.03). In patients with end-stage ILD, CA 19-9 may represent a marker of disease severity, whereas its level is inversely correlated with functional decline, particularly among IPF rapid progressors.

Systematic Review and Metanalysis of Oncomarkers in IPF Patients and Serial Changes of Oncomarkers in a Prospective Italian Real-Life Case Series

“…Kodama T et al suggested that clinicians pay attention to evidence that elevated serum levels of CA19.9 may be related to poor prognosis in IPF patients [ 9 ]. Balestro et al recently reported CA 19-9 as a disease severity marker in patients with end-stage ILD, demonstrating an inverse correlation of this oncomarker with functional decline, particularly among patients with rapidly progressive IPF [ 7 ]. Ca15.3 has been studied in relation to the pathogenesis of IPF, and it has been associated with survival and disease severity, due to an inverse correlation between DLCO and high-resolution computed tomography (HRCT) findings [ 15 ].…”

“…Serum samples for assay of the following proteins/oncomarkers were drawn at baseline t0 and every 6 months of follow-up (6 months (t1), 12 months (t2), 18 months (t3), and 24 months (t4)): chitotriosidase (chitinase-1), carcinoembryonic antigen (CEA), cancer antigen 15-5 (Ca15-3), neuron-specific enolase (NSE), cancer antigen 19-9 (Ca19-9), cytokeratin fragment 21-1 (Cyfra 21.1), and cancer antigen 125 (Ca-125). Oncomarkers and chitotriosidase were assayed as previously reported [ 7 , 8 , 10 , 23 , 39 , 42 , 43 ].…”

“…In the PRO-FILE (prospective observation of fibrosis in the lung clinical endpoints) study, some of these oncomarkers, especially Ca19.9 and Ca125, were associated with increased mortality [6]. Very recently Balestro et al corroborated the prognostic value of Ca19.9 in end-stage IPF [7]. Although several authors have reported high concentrations of common oncomarkers, including carcinoembryonic antigen (CEA) [8], cancer antigen 19.9 (Ca19.9) [9], 15.3 (Ca15.3) [10], 125 (Ca125) [8], and Krebs von den Lungen-6 (KL-6) [11][12][13][14], in IPF, little data is available on the prognostic role of all these markers, taken together, and their interactions, in IPF progression [9,15].…”

Non-invasive Biomarkers of Idiopathic Pulmonary Fibrosis and Lung Cancer

“…-Carbohydrate antigen 19-9 (CA 19-9): this glycoprotein produced by epithelium is a common gastrointestinal, mainly pancreatic, tumor biomarker. Its elevated levels in serum, have also been observed in benign respiratory diseases such as IPF and ILDs in general [25][26][27] .…”

Immune Stroma in Lung Cancer and Idiopathic Pulmonary Fibrosis: A Common Biologic Landscape?

“…By stratifying patient in terms of disease progression rate, Ca 19.9 level emerges as being inversely correlated to lung function decline, mainly in those patients who rapidly progress. Increased Ca 19.9 levels are associated with increased levels in the end-stage IPF, irrespective of treatment setting [ 106 ]. Indeed, fewer data are available on the potential role of circulating oncomarker levels in predicting response to therapy.…”