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
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 centr...
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Nature Portfolio
2019
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oai:doaj.org-article:5b0e5c7b0b8f451b8d8d0ea7d92d310f2021-12-02T15:08:08ZDifferential expression of individual transcript variants of PD-1 and PD-L2 genes on Th-1/Th-2 status is guaranteed for prognosis prediction in PCNSL10.1038/s41598-019-46473-52045-2322https://doaj.org/article/5b0e5c7b0b8f451b8d8d0ea7d92d310f2019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-46473-5https://doaj.org/toc/2045-2322Abstract 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.Yasuo TakashimaAtsushi KawaguchiRyuichi SatoKenichi YoshidaAzusa HayanoJumpei HommaJunya FukaiYasuo IwadateKoji KajiwaraShin IshizawaHiroaki HondohMasakazu NakanoSeishi OgawaKei TashiroRyuya YamanakaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-13 (2019) |
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Medicine R Science Q |
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Medicine R Science Q Yasuo Takashima Atsushi Kawaguchi Ryuichi Sato Kenichi Yoshida Azusa Hayano Jumpei Homma Junya Fukai Yasuo Iwadate Koji Kajiwara Shin Ishizawa Hiroaki Hondoh Masakazu Nakano Seishi Ogawa Kei Tashiro Ryuya Yamanaka 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 |
| description |
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. |
| format |
article |
| author |
Yasuo Takashima Atsushi Kawaguchi Ryuichi Sato Kenichi Yoshida Azusa Hayano Jumpei Homma Junya Fukai Yasuo Iwadate Koji Kajiwara Shin Ishizawa Hiroaki Hondoh Masakazu Nakano Seishi Ogawa Kei Tashiro Ryuya Yamanaka |
| author_facet |
Yasuo Takashima Atsushi Kawaguchi Ryuichi Sato Kenichi Yoshida Azusa Hayano Jumpei Homma Junya Fukai Yasuo Iwadate Koji Kajiwara Shin Ishizawa Hiroaki Hondoh Masakazu Nakano Seishi Ogawa Kei Tashiro Ryuya Yamanaka |
| author_sort |
Yasuo Takashima |
| 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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| publisher |
Nature Portfolio |
| publishDate |
2019 |
| url |
https://doaj.org/article/5b0e5c7b0b8f451b8d8d0ea7d92d310f |
| work_keys_str_mv |
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1718388252995485696 |