| Autor: |
Shuping Zhuang, Tingting Chen, Yawei Li, Yuquan Wang, Liqiang Ai, Yiding Geng, Min Zou, Kaidong Liu, Huanhuan Xu, Linzhu Wang, Zhangxiang Zhao, Zhiqiang Chang, Yunyan Gu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Molecular Therapy: Nucleic Acids, Vol 26, Iss , Pp 1014-1026 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2162-2531 |
| DOI: |
10.1016/j.omtn.2021.10.014 |
| Popis: |
Pancreatic cancer (PC) with homologous recombination deficiency (HRD) has been reported to benefit from poly ADP-ribose polymerase (PARP) inhibitors. However, accurate identification of HRD status for PC patients from the transcriptional level is still a great challenge. Here, based on a relative expression ordering (REO)-based algorithm, we developed an HRD signature including 24 gene pairs (24-GPS) using PC transcriptional profiles from The Cancer Genome Atlas (TCGA). HRD samples classified by 24-GPS showed worse overall survival (p = 4.4E-3 for TCGA; p = 1.2E-3 for International Cancer Genome Consortium-Australia cohort; p = 6.4E-2 for GSE17891; p = 7.5E-2 for GSE57495) and higher HRD scores than non-HRD samples (p = 1.4E-4). HRD samples showed highly unstable genomic characteristics and also displayed HRD-related alterations at the epigenomic and proteomic levels. Moreover, HRD cell lines identified by 24-GPS tended to be sensitive to PARP inhibitors (p = 6.6E-2 for olaparib; p = 2.6E-3 for niraparib). Compared with the non-HRD group, the HRD group presented lower immune scores and CD4/CD8 T cell infiltration proportion. Interestingly, PC tumor cells with co-inhibition of PARP-related genes and ATR showed reduced survival ability. In conclusion, 24-GPS can robustly identify PC patients with HRD status at the individualized level. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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