Abstract
Thioredoxin 1 (Trx1) and haptoglobin (Hp) are known to be involved in pathophysiology. This study was conducted to evaluate their diagnostic significance. We employed an enzyme-linked immunosorbent assay (ELISA) to determine the concentrations of both Trx1 and Hp in sera from female patients with community-acquired pneumonia (CAP) and those with lung cancer. The Trx1 levels remarkably decreased in cases of female patients with CAP, while the Hp levels increased in both female patients with lung cancer and CAP. In addition, the serum levels of Trx1 were not significantly changed in patients with lung cancer, rheumatoid arthritis, and cardiovascular diseases compared to healthy controls. At the cut-off point of 0.396 at A450 nm on the receiver operating characteristic (ROC) curve, Trx1 could discriminate between patients with CAP from normal female controls with a sensitivity of 72.5%, a specificity of 89.8%, and area under the ROC curve (AUC) of 0.877 ± 0.040. The serum levels of Trx1 in female CAP patients were inversely correlated with the levels of Hp (p < 0.05). The characteristic reduction in serum Trx1 levels, especially in female CAP patients, indicates that Trx1 could be used as a diagnostic marker for CAP. The advantage of serum Trx1 over Hp in discriminating female CAP patients among female patients who have a positive serum level of Hp suggests the use of Trx1 as an excellent combination marker with Hp for the specific diagnosis of CAP and lung carcinoma, because serum Hp levels increase in female patients with lung cancer and those with CAP without selectivity.
Highlights
Ɖ ůĞǀĞůƐ ŝŶĐƌĞĂƐĞĚ ŝŶ ďŽƚŚ ĨĞŵĂůĞ ƉĂƟĞŶƚƐ ǁŝƚŚ ůƵŶŐ ĐĂŶĐĞƌ ĂŶĚ W /Ŷ ĂĚĚŝƟŽŶƚŚĞ ƐĞƌƵŵ ůĞǀĞůƐ ŽĨ dƌdžϭ ǁĞƌĞ
ǀŝĂ ƚŚĞ ƚǁŽ ĐLJƐƚĞŝŶĞ ƌĞƐŝĚƵĞƐ ϭ͘ dŚĞ ĞdžĐŚĂŶŐĞ ƌĞĂĐƟŽŶ ĂĐƟǀŝƚLJ ŝƐ ŝŶǀŽůǀĞĚ
ŽƉLJƌŝŐŚƚdŚŝƐ ŝƐ ĂŶ ŽƉĞŶͲĂĐĐĞƐƐ ĂƌƟĐůĞ ĚŝƐƚƌŝďƵƚĞĚ ƵŶĚĞƌ ƚŚĞ ƚĞƌŵƐ ŽĨ ƚŚĞ ƌĞĂƟǀĞ ŽŵŵŽŶƐ ƩƌŝďƵƟŽŶ >ŝĐĞŶƐĞ ǁŚŝĐŚ ƉĞƌŵŝƚƐ ƵŶƌĞƐƚƌŝĐƚĞĚ ƵƐĞ ĚŝƐƚƌŝďƵƟŽŶ ĂŶĚ ƌĞƉƌŽĚƵĐƟŽŶ ŝŶ ĂŶLJ ŵĞĚŝƵŵ ƉƌŽǀŝĚĞĚ ƚŚĞ ŽƌŝŐŝŶĂů ĂƵƚŚŽƌ ĂŶĚ ƐŽƵƌĐĞ ĂƌĞ ĐƌĞĚŝƚĞĚ
Summary
DŚĞ ϭϮͲŬĂ ŚƵŵĂŶ ĐLJƚŽƐŽůŝĐ ƚŚŝŽƌĞĚŽdžŝŶ ϭ ;dƌdžϭͿ ĐŽŶƚĂŝŶƐ Ă ƌĞĚŽdžͲĂĐƟǀĞ ĚŝƚŚŝŽů ŵŽŝĞƚLJ ŝŶ ŝƚƐ ĐŽŶƐĞƌǀĞĚ ĂĐƟǀĞͲƐŝƚĞ ƐĞƋƵĞŶĐĞ ;ʹLJƐ'ůLJWƌŽLJƐͿ ϭ͘ /Ŷ ƌĞƐƟŶŐ ĐĞůůƐdƌdžϭ ƌĞƐŝĚĞƐ ŝŶ ƚŚĞ ĐLJƚŽƐŽůďƵƚ ĂĐƟǀĂƟŽŶ ďLJ Ă ǁŝĚĞ ǀĂƌŝĞƚLJ ŽĨ ƐƟŵƵůŝ ůĞĂĚƐ ƚŽ ŝƚƐ ƚƌĂŶƐůŽĐĂƟŽŶ ƚŽ ƚŚĞ ŶƵĐůĞƵƐ Žƌ ƚŚĞ ƐĞĐƌĞƟŽŶ ŽĨ ƚŚŝƐ ƉƌŽƚĞŝŶ Ϯϯ͘ dƌdžϭ ĐĂƚĂůLJƐĞƐ ƚŚŝŽůͲ ĚŝƐƵůĮĚĞ ĞdžĐŚĂŶŐĞ ƌĞĂĐƟŽŶƐ ǀŝĂ ƚŚĞ ƚǁŽ ĐLJƐƚĞŝŶĞ ƌĞƐŝĚƵĞƐ ϭ͘ dŚĞ ĞdžĐŚĂŶŐĞ ƌĞĂĐƟŽŶ ĂĐƟǀŝƚLJ ŝƐ ŝŶǀŽůǀĞĚ ŝŶ ǀĂƌŝŽƵƐ ďŝŽůŽŐŝĐĂů ĂĐƟǀŝƟĞƐŝŶĐůƵĚŝŶŐ ƚŚĞ ƌĞŐƵůĂƟŽŶ ŽĨ ƚŚĞ ĂĐƟǀŝƚLJ ŽĨ ƚƌĂŶƐĐƌŝƉƟŽŶ ĨĂĐƚŽƌƐ ƐƵĐŚ ĂƐ ŶƵĐůĞĂƌ ĨĂĐƚŽƌ ;E&ͲʃͿ ĂŶĚ ĂĐƟǀĂƚŽƌ ƉƌŽƚĞŝŶͲϭ Ϯκ͘ DŽƌĞŽǀĞƌƌĞĚƵĐĞĚ dƌdžϭ ŝŶŚŝďŝƚƐ ĂƉŽƉƚŽƐŝƐ ďLJ ďŝŶĚŝŶŐ ƚŽ ĂƉŽƉƚŽƐŝƐ ƐŝŐŶĂůŝŶŐ ŬŝŶĂƐĞ ϭρ͘ dŚĞ ĞdžƚƌĂĐĞůůƵůĂƌ dƌdžϭ ĂĐƚƐ ĂƐ Ă ĐŚĞŵŽŬŝŶĞ ĂŶĚ ĐŽͲĐLJƚŽŬŝŶĞ ƐƟŵƵůĂƟŶŐ ĐLJƚŽŬŝŶĞ ƐĞĐƌĞƟŽŶ ĂŶĚ ĐĞůů ƉƌŽůŝĨĞƌĂƟŽŶ ςϳ͘ ƵĞ ƚŽ ƚŚĞƐĞ ďŝŽůŽŐŝĐĂů ĂĐƟǀŝƟĞƐdƌdžϭƐ ŝŶǀŽůǀĞŵĞŶƚ ŝŶ ƌĞĚŽdž ƉƌŽĐĞƐƐĞƐ ĐŽƵůĚ ďĞ ŝŵƉŽƌƚĂŶƚ ŝŶ ƚŚĞ ƉĂƚŚŽƉŚLJƐŝŽůŽŐLJ ŽĨ ĐĂŶĐĞƌ ĂŶĚ ŝŶŇĂŵŵĂƟŽŶ ρΘ͘. Ϯϭ WĂƟĞŶƚƐ ĂŶĚ ƐĂŵƉůĞ ĐŽůůĞĐƟŽŶ ůů ƐĞƌĂ ŽĨ ŶŽƌŵĂů ƉĞƌƐŽŶƐ ;ĐŽŶƚƌŽůͿ ĂŶĚ ƉĂƟĞŶƚƐ ǁŝƚŚ W ĂŶĚ ůƵŶŐ ĐĂŶĐĞƌ ǁĞƌĞ ŽďƚĂŝŶĞĚ ĨƌŽŵ ĂƵĐĂƐŝĂŶƐtŚŝƚĞdŚĞ ƐĞƌĂ ĂŶĚ ƚŚĞ ĐůŝŶŝĐĂů ŝŶĨŽƌŵĂƟŽŶ ĨŽƌ ƚŚĞ ƐƚƵĚLJ ƉĂƌƟĐŝƉĂŶƚƐ ǁĞƌĞ ƉƌŽǀŝĚĞĚ ĨƌŽŵ ƐƚĞƌĂŶĚ ŝŽƐĐŝĞŶĐĞ ;ŚƩƉͬͬǁǁǁĂƐƚĞƌĂŶĚďŝŽĐŽŵͿ ĂŶĚ ŝŽ^ĞƌǀĞ ;ŚƩƉͬͬǁǁǁďŝŽƐĞƌǀĞĐŽŵͿ ĂŶĚ ĂƌĞ ƐƵŵŵĂƌŝƐĞĚ ŝŶ dĂďůĞ ϭ ĂŶĚ dĂďůĞ Ϯůů ƐĂŵƉůĞƐ ǁĞƌĞ ĐŽůůĞĐƚĞĚ ĨƌŽŵ ƚŚĞŝƌ ĐŽůůĂďŽƌĂƟŶŐ ĐůŝŶŝĐĂů ƐŝƚĞƐ ǁŝƚŚ ĨƵůů ĂĚŚĞƌĞŶĐĞ ƚŽ ƉƌŽƉĞƌ ŝŶĨŽƌŵĞĚ ĐŽŶƐĞŶƚ ĂƐ ǁĞůů ĂƐ ƚŚĞŝƌ ƐƚƌŝĐƚ ŝŶƐƟƚƵƟŽŶĂů ƌĞǀŝĞǁ ďŽĂƌĚ ĂŶĚ ,ĞĂůƚŚ /ŶƐƵƌĂŶĐĞ WŽƌƚĂďŝůŝƚLJ ĂŶĚ ĐĐŽƵŶƚĂďŝůŝƚLJ Đƚ ĐŽŵƉůŝĂŶĐĞdŽ ŵĂŬĞ ƚŚĞŵ ƐƵŝƚĂďůĞ ĨŽƌ Ă ďŝŽŵĂƌŬĞƌ ƐƚƵĚLJ Ăůů ƚŚĞ ƐĞƌĂ ǁĞƌĞ ĐŽůůĞĐƚĞĚ ĂŶĚ ƚƌĞĂƚĞĚ ĂĐĐŽƌĚŝŶŐ ƚŽ ƚŚĞ ŝŶƐƚƌƵĐƟŽŶƐ ŽĨ ƚŚĞ &ŽŽĚ ĂŶĚ ƌƵŐ ĚŵŝŶŝƐƚƌĂƟŽŶ ĂŶĚ ƚŚĞ EĂƟŽŶĂů ĂŶĐĞƌ /ŶƐƟƚƵƚĞůů ƐĞƌƵŵ ƐĂŵƉůĞƐ ǁĞƌĞ ƚĂŬĞŶ ƉƌŝŽƌ ƚŽ ƐƵƌŐĞƌLJ ĂŶĚͬŽƌ ƚŚĞ ĐŽŵŵĞŶĐĞŵĞŶƚ ŽĨ ĐŚĞŵŽƚŚĞƌĂƉĞƵƟĐ ŵĞĚŝĐĂƟŽŶƐ ^ĂŵƉůĞƐ ǁĞƌĞ ƉƌŽǀŝĚĞĚ ĨƌŽŵ ƐƵďũĞĐƚƐ ǁŚŽ ǁĞƌĞ ĚĞƚĞƌŵŝŶĞĚ ƚŽ ŚĂǀĞ ĐĂƌĚŝŽǀĂƐĐƵůĂƌ ĚŝƐĞĂƐĞ ŝĨ ƚŚĞLJ ŵĞƚ ƚŚĞ EĞǁ zŽƌŬ ,ĞĂƌƚ ƐƐŽĐŝĂƟŽŶ ĐƌŝƚĞƌŝĂ ϭΘ͖ ŚŽǁĞǀĞƌŝĨ ƚŚĞ ŝŶĨŽƌŵĂƟŽŶ ĨŽƌ ĐůĂƐƐŝĮĐĂƟŽŶ ǁĂƐ ŶŽƚ ĂǀĂŝůĂďůĞ ŽƚŚĞƌ ĚŝĂŐŶŽƐƟĐ ĐƌŝƚĞƌŝĂ ŽĨ ĐĂƌĚŝŽǀĂƐĐƵůĂƌ ĚŝƐĞĂƐĞ ĚĞƚĞƌŵŝŶĞĚ ďLJ ĞĐŚŽĐĂƌĚŝŽŐƌĂŵ ĐŽƌŽŶĂƌLJ ĂŶŐŝŽŐƌĂŵ Žƌ ŚŝŐŚ ƚƌŽƉŽŶŝŶ ůĞǀĞůƐ ĨŽůůŽǁŝŶŐ Ă ĐĂƌĚŝĂĐ ĞƉŝƐŽĚĞ ǁĞƌĞ ĂůƐŽ ŝŶĐůƵĚĞĚ ^ĂŵƉůĞƐ ǁĞƌĞ ƉƌŽǀŝĚĞĚ ĨƌŽŵ ƐƵďũĞĐƚƐ ǁŝƚŚ ƌŚĞƵŵĂƚŽŝĚ ĂƌƚŚƌŝƟƐ ǁŚŽ ŵĞƚ ƚŚĞ ŵĞƌŝĐĂŶ ŽůůĞŐĞ ŽĨ ZŚĞƵŵĂƚŽůŽŐLJ ĐƌŝƚĞƌŝĂ ĨŽƌ ƌŚĞƵŵĂƚŽŝĚ ĂƌƚŚƌŝƟƐ ϭε ĂŶĚ ǁŚŽ ǁĞƌĞ ƌŚĞƵŵĂƚŽŝĚ ĨĂĐƚŽƌ ƉŽƐŝƟǀĞ EŽƌŵĂů ĐŽŶƚƌŽů ƐĞƌƵŵ ƐĂŵƉůĞƐ ǁĞƌĞ ƉƌŽǀŝĚĞĚ ĨƌŽŵ ƐƵďũĞĐƚƐ ǁŚŽ ǁĞƌĞ ŚĞĂůƚŚLJ ĂŶĚ ŚĂĚ ŶŽ ŬŶŽǁŶ ĐůŝŶŝĐĂů ĐŽŶĚŝƟŽŶƐ ;ƌŝĐ D >ĂŶŐůŽŝƐ ŝŽ^ĞƌǀĞ WĞƌƐŽŶĂů ŽŵŵƵŶŝĐĂƟŽŶϯϭ DĂƌĐŚ ϮϬϭρͿ. Ϯϯ ^ƚĂƟƐƟĐĂů ĂŶĂůLJƐŝƐ 'ƌĂƉŚWĂĚ WƌŝƐŵ ǀĞƌƐŝŽŶ ρϬκ ĨŽƌ tŝŶĚŽǁƐ ;'ƌĂƉŚWĂĚ ^ŽŌǁĂƌĞh^ Ϳ ĂŶĚ DĞĚĂůĐ ƐƚĂƟƐƟĐĂů ƐŽŌǁĂƌĞ ǀĞƌƐŝŽŶ ϭϮκϬϬ ;DĞĚĂůĐ ^ŽŌǁĂƌĞ ďǀďĂ ĞůŐŝƵŵͿ ǁĞƌĞ ƵƐĞĚ ĨŽƌ ƐƚĂƟƐƟĐĂů ĂŶĂůLJƐĞƐtĞ ƵƐĞĚ ƚŚĞ WĞĂƌƐŽŶ ƉƌŽĚƵĐƚͲŵŽŵĞŶƚ ĐŽƌƌĞůĂƟŽŶ ĐŽĞĸĐŝĞŶƚ ƚŽ ƚĞƐƚ ĨŽƌ ĂƐƐŽĐŝĂƟŽŶƐ ďĞƚǁĞĞŶ ĚŝīĞƌĞŶƚ ǀĂƌŝĂďůĞƐdŚĞ ƚ ƚĞƐƚƐ ĂŶĚ ŽŶĞͲǁĂLJ ĂŶĂůLJƐŝƐ ŽĨ ǀĂƌŝĂŶĐĞ ; EKs Ϳ ƚĞƐƚƐ ǁĞƌĞ ƉĞƌĨŽƌŵĞĚ ƚŽ ĐĂůĐƵůĂƚĞ ƚŚĞ p ǀĂůƵĞdŚĞ p ǀĂůƵĞ ǁĂƐ ĐŽŶƐŝĚĞƌĞĚ ƚŽ ďĞ ƐƚĂƟƐƟĐĂůůLJ ƐŝŐŶŝĮĐĂŶƚ ŝĨ p ф ϬϬρdĞƐƟŶŐ ĨŽƌ ŶŽƌŵĂůŝƚLJ ŽĨ ƚŚĞ ĚĂƚĂ ǁĂƐ ƉĞƌĨŽƌŵĞĚ ƵƐŝŶŐ ƚŚĞ ͛ ŐŽƐƟŶŽͲWĞĂƌƐŽŶ ŶŽƌŵĂůŝƚLJ ƚĞƐƚ
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