In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 77, No. 13_Supplement ( 2017-07-01), p. 384-384
Abstract:
Aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMP) is the multiple tRNA synthetase complex protein called the multi-tRNA complex (MRC). In cancer, the splicing variant of AIMP2 derives a several signaling cascades, which are crucial for cancer proliferation. Detecting an exon-2 depleted splicing variant (AIMP2-DX2) is an issue of growing importance in cancer therapy. This study suggests the evidence for interrelation between the AIMP2-DX2 and cancer development. We analyzed AIMP2 and AIMP2-DX2 gene expression and their ratio on 7 commercial cancer cell lines and Multiple myeloma patient derived 536MM cell line by RT-PCR and targeted RNA sequencing. Extended this profile, the distribution of AIMP2-DX2/AIMP2 ratio and AIMP2-related major cancer pathways were analyzed using the samples in the ICGC/TCGA database. Over 23 cancer types, 753 samples were used in WTS analysis. In the DEG set analysis, 10 pre-defined major cancer pathways were analyzed among 16 cancer types. Some cancer types, especially acute myeloid leukemia (AML) showed most significant association with AIMP2-DX2 in terms of cancer signaling pathways. We focused on clinical implications of AIMP2-DX2/AIMP2 ratio in the ICGC/TCGA database. 19 AML samples were used, Overall survival (OS) showed that patients with AIMP2-DX2/AIMP2 ratio higher than Q1 shows poor OS and Most of the genes including MEK1/2, ERK, MNK1/2 in this pathway had positive association with AIMP2-DX2/AIMP2 ratio. In colon carcinoma and hepatocellular carcinoma, OS curves had a tendency in a similar way to AML. For the clinical validation of the prognostic value of AIMP2-DX2, 51 AML patients were included in this analysis. The correlation between AIMP2-DX2 expression and survival outcomes was investigated in clinical validation cohort of AML. The AIMP2-DX2-positive group had significantly inferior OS rate and had worse RFS compare to AIMP2-DX2-negative group. Our sequential data shows that the AIMP2-DX2/AIMP2 expression and their ratio can possibly be an indicator to measure malignancy of various cancer types. Citation Format: Dong Chan Kim, Ryul Kim, Daeyoon Kim, Hyojin Song, Dong-Yeop Shin, Inho Kim, Kwang-Sung Ahn, Nam Hoon Kwon, Sunghoon Kim, Sung-Soo Yoon, Youngil Koh. The implications of splicing variant of AIMP2 lacking exon 2 among various cancer types: An analysis of the ICGC/TCGA database and clinical validation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 384. doi:10.1158/1538-7445.AM2017-384
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2017-384
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2017
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
