Elevated fecal M2-pyruvate kinase in children with cystic fibrosis: a clue to the increased risk of intestinal malignancy in adulthood?
OBJECTIVE
Adult patients with cystic fibrosis (CF) have an increased risk of gastrointestinal malignancies. We hypothesized that increased intestinal cell turnover beginning in childhood may explain the increased risk of malignancy in early adulthood. Therefore, we aimed to measure fecal M2-pyruvate kinase (M2-PK), a biomarker of intestinal cell turnover, in children with CF. To assess whether the increased cell turnover is secondary to intestinal inflammation, the secondary aims were to measure fecal calprotectin and evaluate its association with fecal M2-PK.


METHODS
Fecal samples, for M2-PK and calprotectin measurements, were prospectively collected from children with CF and healthy controls (HC).


RESULTS
Thirty-three children with CF (mean [standard deviation] 7.3 [3.8] years old; 29 pancreatic insufficient [PI]) were enrolled and compared with 33 age-matched HC. Fecal M2-PK in CF patients (median [interquartile range, IQR]: 4.7 [1.5-9.7]) was greater than HC (1.0 [1.0-1.0] U/mL; P < 0.0001), and higher in PI (median [IQR]: 5.1 [1.8-13.7]) than pancreatic sufficient patients (1.0 [1.0-1.0] U/mL; P = 0.002). Fecal calprotectin was significantly elevated in CF than HC (median [IQR] 61.3 [43.8-143.8] vs 19.5 [19.5-35.1] mg/kg; P < 0.0001). However, there was no correlation between fecal M2-PK and fecal calprotectin levels among subjects with CF (r = 0.29; P = 0.1).


CONCLUSIONS
Increased intestinal cell turnover is present in children with PI CF. The lack of relationship between fecal M2-PK and calprotectin suggests that contributing factor(s) other than inflammation may be present.
Discipline of Paediatrics, School of Women's and Children's Health, Medicine, University of New South Wales, Sydney, New South Wales, Australia.
Tamara
T
Pang
Steven T
ST
Leach
Tamarah
T
Katz
Adam
A
Jaffe
Andrew S
AS
Day
Chee Y
CY
Ooi
D000293:Adolescent; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003110:Colonic Neoplasms / Q000209:etiology; D003550:Cystic Fibrosis / Q000150:complications / Q000473:pathology*; D005243:Feces / Q000737:chemistry / Q000201:enzymology*; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation; D007410:Intestinal Diseases / Q000150:complications / Q000175:diagnosis* / Q000473:pathology; D007422:Intestines / Q000473:pathology; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis; D008297:Male; D011446:Prospective Studies; D011770:Pyruvate Kinase / Q000032:analysis*; D012306:Risk
D015415:Biomarkers; D039841:Leukocyte L1 Antigen Complex; D011770:Pyruvate Kinase
biological markers; cystic fibrosis; inflammation; intestinal neoplasms; pyruvate kinase