Analysis of microRNA Expression Profile in Angioimmunoblastic T-Cell Lymphoma and Peripheral T-Cell Lymphoma-Not Otherwise Specified Shows Diagnostic Potential, and Utility for Predicting Therapeutic Response and Prognosis
Soo-Jeong Nam, Yoon Kyung Jeon, Chul Woo Kim. Seoul National University College of Medicine, Seoul, Korea
Background: Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) are aggressive neoplasms demanding diagnostic and prognostic molecular markers.
Design: We investigated expression profile for 17 miRNAs, which were selected by biologic relevance in lymphoma and immune system, in 24 AITL and 23 PTCL-NOS patients using formalin-fixed paraffin-embedded tissue and real-time reverse transcription PCR.
Results: The mean relative expression level of miR-155 and miR-21 were 5.56-times and 6.72-times higher in disease group (i.e., encompassing both AITL and PTCL-NOS) than control group (i.e., non-neoplastic lymphoid tissue), respectively (P = 0.033 and P < 0.001). MiR-29b expression was down-regulated in disease group compared with control (P = 0.033). In terms of miRNA expression and chemotherapy response, miR-101, miR-103, miR-221, miR-106a, and miR-223 were down-regulated in patients who achieved complete response (CR) to initial chemotherapy (P = 0.007, P = 0.038, P = 0.003, P < 0.001, and P = 0.007, respectively). MiR-221 was also found down-regulated in responders (i.e., CR and partial response) compared to non-responders who showed stable or progressive disease (P = 0.032). MiR-29b was more down-regulated in non-responder rather than in responder, which was only significant in the cases of AITL (P = 0.039) but not in PTCL-NOS. In univariate survival analysis, patients with up-regulated miR-181a showed much better overall survival (OS) and progression free survival (PFS) (P = 0.002; P = 0.025), particularly analyzed in AITL group with strong statistical significance. In addition, overexpression of miR-17, miR-21, and miR-125b were also significantly related with better OS of patients. On the other hand, patients with higher level of miR-106a had a significantly shorter OS or PFS than those with low level of miR-106a (P = 0.021; P = 0.013). Multivariate analysis revealed that low miR-125b was an independent predictor for shorter OS (P = 0.003; HR = 5.977), and low miR-181a was an independent poor prognostic indicator for PFS (P = 0.019; HR = 3.131).
Conclusions: Our study suggested that different kinds of miRNAs might be involved in the neoplastic transformation and progression of AITL and PTCL-NOS with complicated influence on the response to chemotherapy and prognosis. We also found several important candidate miRNAs for the development of diagnostic and prognostic marker in peripheral T-cell lymphoma.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 194, Wednesday Morning