Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer.
The involvement of iron and inflammation parameters on overall survival in non-small-cell lung cancer (NSCLC) patients was studied. Furthermore, transferrin receptors 1 (TfR1) and ferritin expression in tumor tissue, tumor stroma, and normal lung tissue were analyzed. Iron metabolism and inflammation parameters were determined by automated laboratory measurements at the time of diagnosis. TfR1 and ferritin expression were determined by immuno-histochemical methods. About 50% of patients survived 12 months only. At the time of diagnosis more than half of the patients had anemia and significantly elevated serum ferritin. Iron content of serum ferritin (ICF) was below the reference values in 90% of patients. Furthermore, ICF showed positive correlation with iron metabolic parameters and survival but negative correlation with serum ferritin and ESR. The expression of TfR1 and ferritin in tumor cells was observed in 88% or 62% of patients, respectively. Tumor stroma was TfR1 negative and sporadically ferritin positive. Tumor tissue ferritin expression showed negative correlation with serum iron and hematokrit (Ht), and positive correlation with ferritin, erythrocyte sedimentation rate (ESR), alpha-1 globulin, and alpha-2 globulin. Positive correlation was found between TfR1 expression in tumor tissue and alpha-globulin. The correlation between TfR1/ferritin expression in tumor tissue and ICF or survival was not observed. Therefore, we conclude that elevated serum ferritin in sera of NSCLC patients is the result of inflammation and oxidative stress rather than body iron overload. Higher expression of ferritin in tumor tissue may be the consequence of iron deficiency or local toxicity induced by environmental factors.
Kukulj
Suzana
S
University Hospital for Lung Diseases Jordanovac, 10000 Zagreb, Croatia.
Jaganjac
Morana
M
Boranic
Milivoj
M
Krizanac
Simun
S
Santic
Zarko
Z
Poljak-Blazi
Marija
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000510:Alpha-Globulins / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D001799:Blood Sedimentation; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D005293:Ferritins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000473:pathology; D019189:Iron Metabolism Disorders / Q000097:blood* / Q000235:genetics / Q000473:pathology; D008175:Lung Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics; D011990:Receptors, Transferrin / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics; D015996:Survival Rate / Q000639:trends
D000510:Alpha-Globulins; D015703:Antigens, CD; C068126:CD71 antigen; D011990:Receptors, Transferrin; C028184:alpha-1 serum globulin; C075761:alpha2-euglobulin; D005293:Ferritins