The elevation of serum napsin A in idiopathic pulmonary fibrosis, compared with KL-6, surfactant protein-A and surfactant protein-D

BMC Pulmonary Medicine

Hiromasa Inoue⁵  Hirohito Tsubouchi³  Takashi Hirano⁴  Masahiro Maeda¹  Tsuyoshi Nosaki³  Go Tsukuya⁵  Masakazu Yanagi²  Hirofumi Uto³  Tsutomu Hamada⁵  Takuya Samukawa⁵ 

[1] Department of Research & Development, Immuno-Biological Laboratories Co., Ltd, Fujioka, Gunma, Japan;Department of Surgical Oncology and Digestive Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan;Department of Digestive and Lifestyle Related Disease, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan;Todachuo General Hospital, Toda, Saitama, Japan;Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan

关键词: SP-D;    SP-A;    Napsin A;    KL-6;    Idiopathic interstitial pneumonia;    Biomarker;   

Others  :  1161064
DOI  :  10.1186/1471-2466-12-55

 received in 2012-03-02, accepted in 2012-08-23,  发布年份 2012

【 摘 要 】

Background

Napsin A, an aspartic protease, is mainly expressed in alveolar type-II cells and renal proximal tubules and is a putative immunohistochemical marker for pulmonary adenocarcinomas. This study sought to determine whether napsin A could be measured in the serum to evaluate its relationship to idiopathic pulmonary fibrosis (IPF) and determine whether renal dysfunction might affect serum napsin A levels.

Methods

Serum levels of napsin A were measured in 20 patients with IPF, 34 patients with lung primary adenocarcinoma, 12 patients with kidney diseases, and 20 healthy volunteers. Surfactant protein (SP)-A, SP-D, and Krebs von den Lungen-6 (KL-6) levels in serum and pulmonary function tests were also evaluated in IPF patients.

Results

Circulating levels of napsin A were increased in patients with IPF, as compared with healthy controls, and they correlated with the severity of disease. Moreover, the serum napsin A levels were not elevated in patients with pulmonary adenocarcinoma or renal dysfunction. The distinguishing point between IPF and the controls was that the area under the receiver operating characteristic curve (ROC) of napsin A was larger than that of KL-6, SP-A, or SP-D.

Conclusion

These findings suggest that serum napsin A may be a candidate biomarker for IPF.

【 授权许可】

   
2012 Samukawa et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Raghu G, Weycker D, Edelsberg J, Bradford WZ, Oster G: Incidence and prevalence of idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2006, 174(7):810-816.
• [2]Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ: Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax 2006, 61(11):980-985.
• [3]Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK, Colby TV, Cordier JF, Flaherty KR, Lasky JA, et al.: An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med 2011, 183(6):788-824.
• [4]Kohno N, Kyoizumi S, Awaya Y, Fukuhara H, Yamakido M, Akiyama M: New serum indicator of interstitial pneumonitis activity. Sialylated carbohydrate antigen KL-6. Chest 1989, 96(1):68-73.
• [5]Takahashi H, Fujishima T, Koba H, Murakami S, Kurokawa K, Shibuya Y, Shiratori M, Kuroki Y, Abe S: Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent. Am J Respir Crit Care Med 2000, 162(3 Pt 1):1109-1114.
• [6]Ohnishi H, Yokoyama A, Kondo K, Hamada H, Abe M, Nishimura K, Hiwada K, Kohno N: Comparative study of KL-6, surfactant protein-A, surfactant protein-D, and monocyte chemoattractant protein-1 as serum markers for interstitial lung diseases. Am J Respir Crit Care Med 2002, 165(3):378-381.
• [7]Zhou LF, Jiang L, Li ZH, Kang J: [Change of matrix metalloproteinase-1 and matrix metalloproteinase-7 in serum and bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and sarcoidosis]. Zhonghua Jie He He Hu Xi Za Zhi 2010, 33(6):441-444.
• [8]Song JW, Song JK, Kim DS: Echocardiography and brain natriuretic peptide as prognostic indicators in idiopathic pulmonary fibrosis. Respir Med 2009, 103(2):180-186.
• [9]Prasse A, Probst C, Bargagli E, Zissel G, Toews GB, Flaherty KR, Olschewski M, Rottoli P, Muller-Quernheim J: Serum CC-chemokine ligand 18 concentration predicts outcome in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2009, 179(8):717-723.
• [10]Chuman Y, Bergman A, Ueno T, Saito S, Sakaguchi K, Alaiya AA, Franzen B, Bergman T, Arnott D, Auer G, et al.: Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas. FEBS Lett 1999, 462(1–2):129-134.
• [11]Woischnik M, Bauer A, Aboutaam R, Pamir A, Stanzel F, de Blic J, Griese M: Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis. Eur Respir J 2008, 31(6):1197-1204.
• [12]Hirano T, Gong Y, Yoshida K, Kato Y, Yashima K, Maeda M, Nakagawa A, Fujioka K, Ohira T, Ikeda N, et al.: Usefulness of TA02 (napsin A) to distinguish primary lung adenocarcinoma from metastatic lung adenocarcinoma. Lung Cancer 2003, 41(2):155-162.
• [13]Bishop JA, Sharma R, Illei PB: Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. Hum Pathol 2010, 41(1):20-25.
• [14]du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, Lancaster L, Noble PW, Raghu G, Sahn SA, et al.: Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis. Am J Respir Crit Care Med 2011, 184(4):459-466.
• [15]du Bois RM, Weycker D, Albera C, Bradford WZ, Costabel U, Kartashov A, King TE Jr, Lancaster L, Noble PW, Sahn SA, et al.: Forced vital capacity in patients with idiopathic pulmonary fibrosis: test properties and minimal clinically important difference. Am J Respir Crit Care Med 2011, 184(12):1382-1389.
• [16]American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias: This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med 2002, 165(2):277-304.
• [17]Kobayashi J, Itoh Y, Kitamura S, Kawai T: [Establishment of reference intervals and cut-off value by an enzyme immunoassay for KL-6 antigen, a new marker for interstitial pneumonia]. Rinsho Byori 1996, 44(7):653-658.
• [18]Abe S, Honda Y, Ando M, Saita N, Kida K, Jinno S, Kondo A, Kuroki Y, Akino T: [Clinical significance of levels of lung surfactant protein A in serum, in various lung diseases]. Nihon Kyobu Shikkan Gakkai Zasshi 1995, 33(11):1219-1225.
• [19]Honda Y, Takahashi H, Abe S, Yuminaga K, Saita N, Ando M, Kondo A, Ogasawara Y, Kuroki Y, Akino T: Clinical evaluation of surfactant protein D kit "Yamasa" in various lung disease. Japanese J Med and Pharm Sci 1996, 36(4):809-815.
• [20]Hermans C, Bernard A: Lung epithelium-specific proteins: characteristics and potential applications as markers. Am J Respir Crit Care Med 1999, 159(2):646-678.
• [21]Kuroki Y, Tsutahara S, Shijubo N, Takahashi H, Shiratori M, Hattori A, Honda Y, Abe S, Akino T: Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis. Am Rev Respir Dis 1993, 147(3):723-729.
• [22]Honda Y, Kuroki Y, Matsuura E, Nagae H, Takahashi H, Akino T, Abe S: Pulmonary surfactant protein D in sera and bronchoalveolar lavage fluids. Am J Respir Crit Care Med 1995, 152(6 Pt 1):1860-1866.
• [23]Hirasawa Y, Kohno N, Yokoyama A, Inoue Y, Abe M, Hiwada K: KL-6, a human MUC1 mucin, is chemotactic for human fibroblasts. Am J Respir Cell Mol Biol 1997, 17(4):501-507.
• [24]Al-Salmi QA, Walter JN, Colasurdo GN, Sockrider MM, Smith EO, Takahashi H, Fan LL: Serum KL-6 and surfactant proteins A and D in pediatric interstitial lung disease. Chest 2005, 127(1):403-407.
• [25]Miyazaki K, Kurishima K, Kagohashi K, Kawaguchi M, Ishikawa H, Satoh H, Hizawa N: Serum KL-6 levels in lung cancer patients with or without interstitial lung disease. J Clin Lab Anal 2010, 24(5):295-299.
• [26]Carrillo-de Santa Pau E, Carrillo Arias F, Caso Pelaez E, Muguruza Trueba I, Sanchez Hernandez I, Munoz Molina GM, Moreno Balsalobre R, Sacristan Lopez S, Gomez-Pinillos A, Toledo Lobo Mdel V: Vascular endothelial growth factor (VEGF) serum levels are associated with survival in early stages of lung cancer patients. Cancer Invest 2010, 28(4):393-398.
• [27]Takahashi H, Kuroki Y, Honda Y, Shijubo N, Hirasawa M, Fujishima T, Akino T, Abe S: Lipid analysis and surfactant-associated protein expression in lung adenocarcinoma cells from pleural effusion. Respiration 1996, 63(6):390-396.
• [28]Ueno T, Linder S, Elmberger G: Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer 2003, 88(8):1229-1233.
• [29]Jagirdar J: Application of immunohistochemistry to the diagnosis of primary and metastatic carcinoma to the lung. Arch Pathol Lab Med 2008, 132(3):384-396.
• [30]Dejmek A, Naucler P, Smedjeback A, Kato H, Maeda M, Yashima K, Maeda J, Hirano T: Napsin A (TA02) is a useful alternative to thyroid transcription factor-1 (TTF-1) for the identification of pulmonary adenocarcinoma cells in pleural effusions. Diagn Cytopathol 2007, 35(8):493-497.
• [31]Schauer-Vukasinovic V, Bur D, Kling D, Gruninger F, Giller T: Human Napsin A: expression, immunochemical detection, and tissue localization. FEBS Lett 1999, 462(1–2):135-139.