期刊
ANNALS OF ONCOLOGY
卷 25, 期 1, 页码 182-188出版社
OXFORD UNIV PRESS
DOI: 10.1093/annonc/mdt530
关键词
diffuse large b-cell lymphoma; PI3K/AKT pathway; p-AKT
类别
资金
- Samsung Biomedical Research Institute [SP2-B2-042-2]
- Basic Science Research Program through the National Research Foundation of Korea (NRF)
- Ministry of Education, Science and Technology [2011-0010951]
- National Research Foundation of Korea [2011-0010951] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Background: Oncogenic phosphatidylinositol-3-kinase/serine-threonine kinase (PI3K/AKT) pathway plays a critical role in cell proliferation and growth. Phosphorylated AKT (p-AKT) has been reported to be abnormally overexpressed and to have poor prognostic impact in solid tumors. Patients and methods: To define the clinical implications of p-AKT expression in diffuse large B-cell lymphoma (DLBCL), we calculated arbitrary units (AUs) by multiplying the intensity and the proportion of p-AKT expression and investigated the impact of p-AKT expression on clinical outcomes. We assessed 262 patients with DLBCL. Based on a cutoff value of the upper limit of the third quartile of AUs, 56 patients were classified as high p-AKT and the remaining 206 patients were classified as low p-AKT. Results: The high p-AKT group was closely associated with more advanced stage (stage III-IV, P = 0.02), two or more extranodal involvement (P = 0.03), lactic dehydrogenase elevation (P = 0.03), higher International Prognostic Index risk groups (high intermediate/high, P = 0.02), and the presence of B-symptoms (P = 0.01). The high p-AKT group showed substantially worse overall survival (OS) (median OS, 115.0 months versus not reached, P = 0.004) and progression-free survival (PFS) (median PFS, 25.5 versus 105.8 months, P = 0.019) compared with the low p-AKT group. Multivariate analysis revealed that high p-AKT expression retained its significant poor prognostic impact for OS (hazard ratio 1.7; 95% confidence interval, 1.0-2.7; P = 0.031). The subgroup with high p-AKT expression and concurrent Epstein-Barr virus positivity showed worst prognosis with the median OS and PFS of 15.2 and 7.4 months. Conclusion: DLBCL patients with high p-AKT expression showed distinct clinical features and followed a more rapidly deteriorating clinical course with worse OS and PFS. Thus, a more effective treatment option should be developed for this subset of DLBCL patients, and targeting PI3K/AKT pathway may be a promising therapeutic strategy.
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