Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma
| Autor: | Lizhi He, Yan Gu, Mathilda Jing Chow, Anil Kapoor, Wenjuan Mei, Ying Dong, Damu Tang, Xiaozeng Lin |
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| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
therapy Papillary renal cell carcinomas business.industry Cell growth papillary renal cell carcinoma Neoplasms. Tumors. Oncology. Including cancer and carcinogens biomarkers Synthetic lethality Hypoxia (medical) medicine.disease_cause Article tumorigenesis Immune system Oncology Downregulation and upregulation Cancer research Medicine Cytotoxic T cell medicine.symptom business Carcinogenesis PLK1 RC254-282 OIP5 |
| Zdroj: | Cancers Cancers, Vol 13, Iss 4483, p 4483 (2021) Volume 13 Issue 17 |
| ISSN: | 2072-6694 |
| Popis: | Papillary renal cell carcinoma (pRCC) is an aggressive but minor type of RCC. The current understanding and management of pRCC remain poor. We report here OIP5 being a novel oncogenic factor and possessing robust prognostic values and therapeutic potential. OIP5 upregulation is observed in pRCC. The upregulation is associated with pRCC adverse features (T1P < T2P < CIMP, Stage1 + 2 < Stage 3 < Stage 4, and N0 < N1) and effectively stratifies the fatality risk. OIP5 promotes ACHN pRCC cell proliferation and xenograft formation the latter is correlated with network alterations related to immune regulation, metabolism, and hypoxia. A set of differentially expressed genes (DEFs) was derived from ACHN OIP5 xenografts and primary pRCCs (n = 282) contingent to OIP5 upregulation both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (p < 2 × 10−16) and relapse (p < 2 × 10−16) possibilities. High-risk tumors stratified by Overlap66 risk score possess an immune suppressive environment, evident by elevations in Treg cells and PD1 in CD8 T cells. Upregulation of PLK1 occurs in both xenografts and primary pRCC tumors with OIP5 elevations. PLK1 displays a synthetic lethality relationship with OIP5. PLK1 inhibitor BI2356 inhibits the growth of xenografts formed by ACHN OIP5 cells. Collectively, the OIP5 network can be explored for personalized therapies in management of pRCC patients. |
| Databáze: | OpenAIRE |
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