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Differential expression of individual transcript variants of PD-1 and PD-L2 genes on Th-1/Th-2 status is guaranteed for prognosis prediction in PCNSL.

発表形態:
原著論文
主要業績:
主要業績
単著・共著:
共著
発表年月:
2019年07月
DOI:
10.1038/s41598-019-46473-5
会議属性:
指定なし
査読:
有り
リンク情報:

日本語フィールド

著者:
* Takashima Y, Kawaguchi A, Sato R, Yoshida K, Hayano A, Homma J, Fukai J, Iwadate Y, Kajiwara K, Ishizawa S, Hondoh H, Nakano M, Ogawa S, Tashiro K, Yamanaka R
題名:
Differential expression of individual transcript variants of PD-1 and PD-L2 genes on Th-1/Th-2 status is guaranteed for prognosis prediction in PCNSL.
発表情報:
Sci Rep. 巻: 9 号: 1 ページ: 10004
キーワード:
概要:
In current molecular medicine, next-generation sequencing (NGS) for transcript variant detection and multivariable analyses are valid methods for evaluating gene expression, cancer mechanisms, and prognoses of patients. We conducted RNA-sequencing on samples from patients with primary central nervous system lymphoma (PCNSL) using NGS and performed multivariable analysis on gene expression data and correlations focused on Th-1/Th-2 helper T cell balance and immune checkpoint to identify diagnosis/prognosis markers and cancer immune pathways in PCNSL. We selected 84 transcript variants to limit the analysis range for Th-1/Th-2 balance and stimulatory and inhibitory checkpoints in 31 PCNSLs. Of these, 21 highly-expressed transcript variants were composed of the formulas for prognoses based on Th-1/Th-2 status and checkpoint activities. Using formulas, Th-1low, Th-2high, and stimulatory checkpointhigh resulted in poor prognoses. Further, Th-1highTh-2low was associated with good prognoses. On the other hand, CD40-001high and CD70-001high as stimulatory genes, and LAG3-001high, PDCD1 (PD-1)-001/002/003high, and PDCD1LG2 (PD-L2)-201low as inhibitory genes were associated with poor prognoses. Interestingly, Th-1highTh-2low and Th-1lowTh-2high were correlated with stimulatory checkpointlow as CD70-001low and inhibitory checkpointlow as HAVCR2 (TIM-3)-001low and PDCD1LG2-001/201low, respectively. Focused on the inhibitory checkpoint, specific variants of CD274 (PD-L1)-001 and PDCD1-002 served severe hazard ratios. In particular, PDCD1-002high by a cut off score was associated with poor prognoses, in addition to PDCD1-001/003high, PDCD1LG2-201low, and LAG3-001high. These results mainly suggest that expression of transcript variants of PDCD1 and PDCD1LG2 on the Th-1/Th-2 balance enable prognostic prediction in PCNSL. This study provides insights for development of molecular target therapies and identification of diagnosis/prognosis markers in PCNSL.
抄録:

英語フィールド

Author:
* Takashima Y, Kawaguchi A, Sato R, Yoshida K, Hayano A, Homma J, Fukai J, Iwadate Y, Kajiwara K, Ishizawa S, Hondoh H, Nakano M, Ogawa S, Tashiro K, Yamanaka R
Title:
Differential expression of individual transcript variants of PD-1 and PD-L2 genes on Th-1/Th-2 status is guaranteed for prognosis prediction in PCNSL.
Announcement information:
Sci Rep. Vol: 9 Issue: 1 Page: 10004
An abstract:
In current molecular medicine, next-generation sequencing (NGS) for transcript variant detection and multivariable analyses are valid methods for evaluating gene expression, cancer mechanisms, and prognoses of patients. We conducted RNA-sequencing on samples from patients with primary central nervous system lymphoma (PCNSL) using NGS and performed multivariable analysis on gene expression data and correlations focused on Th-1/Th-2 helper T cell balance and immune checkpoint to identify diagnosis/prognosis markers and cancer immune pathways in PCNSL. We selected 84 transcript variants to limit the analysis range for Th-1/Th-2 balance and stimulatory and inhibitory checkpoints in 31 PCNSLs. Of these, 21 highly-expressed transcript variants were composed of the formulas for prognoses based on Th-1/Th-2 status and checkpoint activities. Using formulas, Th-1low, Th-2high, and stimulatory checkpointhigh resulted in poor prognoses. Further, Th-1highTh-2low was associated with good prognoses. On the other hand, CD40-001high and CD70-001high as stimulatory genes, and LAG3-001high, PDCD1 (PD-1)-001/002/003high, and PDCD1LG2 (PD-L2)-201low as inhibitory genes were associated with poor prognoses. Interestingly, Th-1highTh-2low and Th-1lowTh-2high were correlated with stimulatory checkpointlow as CD70-001low and inhibitory checkpointlow as HAVCR2 (TIM-3)-001low and PDCD1LG2-001/201low, respectively. Focused on the inhibitory checkpoint, specific variants of CD274 (PD-L1)-001 and PDCD1-002 served severe hazard ratios. In particular, PDCD1-002high by a cut off score was associated with poor prognoses, in addition to PDCD1-001/003high, PDCD1LG2-201low, and LAG3-001high. These results mainly suggest that expression of transcript variants of PDCD1 and PDCD1LG2 on the Th-1/Th-2 balance enable prognostic prediction in PCNSL. This study provides insights for development of molecular target therapies and identification of diagnosis/prognosis markers in PCNSL.


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