Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme

被引:24
作者
Cetin, Bulent [1 ]
Gonul, Ipek Isik [2 ]
Gumusay, Ozge [6 ]
Bilgetekin, Irem [4 ]
Algin, Efnan [5 ]
Ozet, Ahmet [3 ]
Uner, Aytug [3 ]
机构
[1] Recep Tayyip Erdogan Univ, Fac Med, Div Med Oncol, Dept Internal Med, TR-53200 Rize, Turkey
[2] Gazi Univ, Fac Med, Dept Pathol, Div Med Oncol, Ankara, Turkey
[3] Gazi Univ, Div Med Oncol, Fac Med, Dept Internal Med, Ankara, Turkey
[4] Dr AY Ankara Oncol Training & Res Hosp, Div Med Oncol, Dept Internal Med, Ankara, Turkey
[5] Ankara Numune Training & Res Hosp, Div Med Oncol, Dept Internal Med, Ankara, Turkey
[6] Gaziosmanpasa Univ, Fac Med, Div Med Oncol, Dept Internal Med, Tokat, Turkey
关键词
carbonic anhydrase IX (CA-IX); glioblastoma; prognostic factor; survival; up-regulation; ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; TUMOR HYPOXIA; THERAPEUTIC TARGET; EXPRESSION; ANGIOGENESIS; PREDICTORS; CARCINOMA; PATHWAYS; SURVIVAL;
D O I
10.1111/neup.12485
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.
引用
收藏
页码:457 / 462
页数:6
相关论文
共 25 条
[1]
Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma [J].
Chia, SK ;
Wykoff, CC ;
Watson, PH ;
Han, C ;
Leek, RD ;
Pastorek, J ;
Gatter, KC ;
Ratcliffe, P ;
Harris, AL .
JOURNAL OF CLINICAL ONCOLOGY, 2001, 19 (16) :3660-3668
[2]
Hypoxia-Inducible Carbonic Anhydrase IX and XII Promote Tumor Cell Growth by Counteracting Acidosis through the Regulation of the Intracellular pH [J].
Chiche, Johanna ;
Ilc, Karine ;
Laferriere, Julie ;
Trottier, Eric ;
Dayan, Frederic ;
Mazure, Nathalie M. ;
Brahimi-Horn, M. Christiane ;
Pouyssegur, Jacques .
CANCER RESEARCH, 2009, 69 (01) :358-368
[3]
Carbonic anhydrase IX and pathological features as predictors of outcome in patients with metastatic clear-cell renal cell carcinoma receiving vascular endothelial growth factor-targeted therapy [J].
Choueiri, Toni K. ;
Regan, Meredith M. ;
Rosenberg, Jonathan E. ;
Oh, William K. ;
Clement, Jessica ;
Amato, Angela M. ;
McDermott, David ;
Cho, Daniel C. ;
Atkins, Michael B. ;
Signoretti, Sabina .
BJU INTERNATIONAL, 2010, 106 (06) :772-778
[4]
RECURSIVE PARTITIONING ANALYSIS OF PROGNOSTIC FACTORS IN 3 RADIATION-THERAPY ONCOLOGY GROUP MALIGNANT GLIOMA TRIALS [J].
CURRAN, WJ ;
SCOTT, CB ;
HORTON, J ;
NELSON, JS ;
WEINSTEIN, AS ;
FISCHBACH, AJ ;
CHANG, CH ;
ROTMAN, M ;
ASBELL, SO ;
KRISCH, RE ;
NELSON, DF .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (09) :704-710
[5]
Hypoxia-regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme [J].
Flynn, Jeannette R. ;
Wang, Libo ;
Gillespie, David L. ;
Stoddard, Gregory J. ;
Reid, Jason K. ;
Owens, Jason ;
Ellsworth, Grant B. ;
Salzman, Karen L. ;
Kinney, Anita Y. ;
Jensen, Randy L. .
CANCER, 2008, 113 (05) :1032-1042
[6]
Giatromanolaki A, 2001, CANCER RES, V61, P7992
[7]
High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer [J].
Ilie, M. ;
Mazure, N. M. ;
Hofman, V. ;
Ammadi, R. E. ;
Ortholan, C. ;
Bonnetaud, C. ;
Havet, K. ;
Venissac, N. ;
Mograbi, B. ;
Mouroux, J. ;
Pouyssegur, J. ;
Hofman, P. .
BRITISH JOURNAL OF CANCER, 2010, 102 (11) :1627-1635
[8]
Expression of hypoxia-lnducible cell-surface transmembrane carbonic anhydrases in human cancer [J].
Ivanov, S ;
Liao, SY ;
Ivanova, A ;
Danilkovitch-Miagkova, A ;
Tarasova, N ;
Weirich, G ;
Merrill, MJ ;
Proescholdt, MA ;
Oldfield, EH ;
Lee, J ;
Zavada, J ;
Waheed, A ;
Sly, W ;
Lerman, MI ;
Stanbridge, EJ .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 158 (03) :905-919
[10]
Endogenous markers of two separate, hypoxia response pathways (hypoxia inducible factor 2 alpha and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial [J].
Koukourakis, MI ;
Bentzen, SM ;
Giatromanolaki, A ;
Wilson, GD ;
Daley, FM ;
Saunders, MI ;
Dische, S ;
Sivridis, E ;
Harris, AL .
JOURNAL OF CLINICAL ONCOLOGY, 2006, 24 (05) :727-735