High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer.
BACKGROUND
Carbonic anhydrase IX (CAIX) is an enzyme upregulated by hypoxia during tumour development and progression. This study was conducted to assess if the expression of CAIX in tumour tissue and/or plasma can be a prognostic factor in patients with non-small cell lung cancer (NSCLC).


METHODS
Tissue microarrays containing 555 NSCLC tissue samples were generated for quantification of CAIX expression. The plasma level of CAIX was determined by ELISA in 209 of these NSCLC patients and in 58 healthy individuals. The CAIX tissue immunostaining and plasma levels were correlated with clinicopathological factors and patient outcome.


RESULTS
CAIX tissue overexpression correlated with shorter overall survival (OS) (P=0.05) and disease-specific survival (DSS) of patients (P=0.002). The CAIX plasma level was significantly higher in patients with NSCLC than in healthy individuals (P<0.001). A high level of CAIX in the plasma of patients was associated with shorter OS (P<0.001) and DSS (P<0.001), mostly in early stage I+II NSCLC. Multivariate Cox analyses revealed that high CAIX tissue expression (P=0.002) was a factor of poor prognosis in patients with resectable NSCLC. In addition, a high CAIX plasma level was an independent variable predicting poor OS (P<0.001) in patients with NSCLC.


CONCLUSIONS
High expression of CAIX in tumour tissue is a predictor of worse survival, and a high CAIX plasma level is an independent prognostic biomarker in patients with NSCLC, in particular in early-stage I+II carcinomas.
Ilie
M
M
Laboratory of Clinical and Experimental Pathology, Louis Pasteur Hospital, Nice, France.
Mazure
N M
NM
Hofman
V
V
Ammadi
R E
RE
Ortholan
C
C
Bonnetaud
C
C
Havet
K
K
Venissac
N
N
Mograbi
B
B
Mouroux
J
J
Pouysségur
J
J
Hofman
P
P
D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000097:blood* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000097:blood / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood* / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D015687:Cell Hypoxia / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D046888:Tissue Array Analysis; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases
Br J Cancer. 2008 Mar 11;98(5):956-64
18268492
Anticancer Res. 2000 May-Jun;20(3A):1527-33
10928066
Cancer Res. 2001 Jul 1;61(13):5262-7
11431368
Lung Cancer. 2009 Sep;65(3):355-62
19162366
Br J Cancer. 2005 Jan 17;92(1):94-101
15558070
Cell Death Differ. 2001 Apr;8(4):367-76
11550088
Neoplasma. 2009;56(4):298-302
19473055
Lung Cancer. 2006 Apr;52(1):59-66
16513206
Lung Cancer. 2006 Dec;54(3):409-18
17030461
Cancer. 2000 Mar 1;88(5):1108-21
10699902
Proc Am Thorac Soc. 2009 Apr 15;6(2):233-41
19349493
Br J Cancer. 2005 Nov 28;93(11):1267-76
16278664
Clin Cancer Res. 2003 Nov 15;9(15):5666-74
14654550
Nat Rev Cancer. 2003 Oct;3(10):721-32
13130303
Curr Opin Biotechnol. 2008 Feb;19(1):19-25
18053705
J Korean Med Sci. 2003 Apr;18(2):196-203
12692416
Lung Cancer. 2009 Jun;64(3):271-6
19022520
Cancer Res. 1999 Nov 15;59(22):5830-5
10582706
J Mol Med (Berl). 2007 Dec;85(12):1301-7
18026916
J Clin Oncol. 2003 Feb 1;21(3):473-82
12560438
Eur J Cancer. 2005 Dec;41(18):2935-47
16310354
Hum Pathol. 2008 Sep;39(9):1317-22
18440050
Clin Cancer Res. 2003 Feb;9(2):802-11
12576453
Control Clin Trials. 1996 Aug;17(4):343-6
8889347
J Urol. 2008 Aug;180(2):510-3; discussion 513-4
18550116
Br J Cancer. 2003 Sep 15;89(6):1067-71
12966427
Clin Cancer Res. 2004 Dec 1;10(23):7925-33
15585626
Int J Oncol. 2004 Apr;24(4):995-1004
15010840
Nat Cell Biol. 2000 Jul;2(7):423-7
10878807
Br J Cancer. 2009 Mar 24;100(6):874-80
19240720
Cancer. 2009 Apr 1;115(7):1448-58
19195047
J Biol Chem. 2008 Oct 10;283(41):27799-27809
18703501
Cancer. 2007 Oct 1;110(7):1532-41
17702091
Cancer Res. 2009 Jan 1;69(1):358-68
19118021
Int J Cancer. 2007 Apr 1;120(7):1451-8
17245699
Nat Rev Drug Discov. 2008 Feb;7(2):168-81
18167490
Chest. 1997 Jun;111(6):1710-7
9187198
Br J Cancer. 2008 Jan 15;98(1):129-36
18026188
Cancer Res. 2002 Apr 1;62(7):1931-4
11929804
J Enzyme Inhib Med Chem. 2004 Jun;19(3):199-229
15499993
Br J Cancer. 2002 Apr 22;86(8):1276-82
11953885
Oncogene. 1994 Jun;9(6):1599-604
8183553
Curr Oncol Rep. 2005 Mar;7(2):109-15
15717944
Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):161-9
18722267
Clin Cancer Res. 2001 Nov;7(11):3399-403
11705854
Lung Cancer. 2005 Sep;49(3):325-35
15935515
Cancer Res. 2000 Dec 15;60(24):7075-83
11156414
Int J Cancer. 2004 Aug 10;111(1):43-50
15185341
Cancer Res. 2001 Sep 1;61(17):6394-9
11522632
Nature. 2006 May 25;441(7092):437-43
16724055