Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma
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...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/13/17/4483 |
| _version_ | 1797521517181927424 |
|---|---|
| author | Mathilda Jing Chow Yan Gu Lizhi He Xiaozeng Lin Ying Dong Wenjuan Mei Anil Kapoor Damu Tang |
| author_facet | Mathilda Jing Chow Yan Gu Lizhi He Xiaozeng Lin Ying Dong Wenjuan Mei Anil Kapoor Damu Tang |
| author_sort | Mathilda Jing Chow |
| collection | DOAJ |
| description | 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 (<i>n</i> = 282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (<i>p</i> < 2 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>×</mo></semantics></math></inline-formula> 10<sup>−16</sup>) and relapse (<i>p</i> < 2 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>×</mo></semantics></math></inline-formula> 10<sup>−16</sup>) 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. |
| first_indexed | 2024-03-10T08:14:34Z |
| format | Article |
| id | doaj.art-61d39682d8b54f9b9ecc52bb34d01708 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:14:34Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-61d39682d8b54f9b9ecc52bb34d017082023-11-22T10:28:10ZengMDPI AGCancers2072-66942021-09-011317448310.3390/cancers13174483Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell CarcinomaMathilda Jing Chow0Yan Gu1Lizhi He2Xiaozeng Lin3Ying Dong4Wenjuan Mei5Anil Kapoor6Damu Tang7Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaCutaneous Biology Research Center, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02115, USADepartment of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaDepartment of Surgery, McMaster University, Hamilton, ON L8S 4K1, CanadaPapillary 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 (<i>n</i> = 282) contingent to OIP5 upregulation; both DEG sets share 66 overlap genes. Overlap66 effectively predicts overall survival (<i>p</i> < 2 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>×</mo></semantics></math></inline-formula> 10<sup>−16</sup>) and relapse (<i>p</i> < 2 <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mo>×</mo></semantics></math></inline-formula> 10<sup>−16</sup>) 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.https://www.mdpi.com/2072-6694/13/17/4483OIP5papillary renal cell carcinomaPLK1tumorigenesistherapybiomarkers |
| spellingShingle | Mathilda Jing Chow Yan Gu Lizhi He Xiaozeng Lin Ying Dong Wenjuan Mei Anil Kapoor Damu Tang Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma Cancers OIP5 papillary renal cell carcinoma PLK1 tumorigenesis therapy biomarkers |
| title | Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma |
| title_full | Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma |
| title_fullStr | Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma |
| title_full_unstemmed | Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma |
| title_short | Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma |
| title_sort | prognostic and therapeutic potential of the oip5 network in papillary renal cell carcinoma |
| topic | OIP5 papillary renal cell carcinoma PLK1 tumorigenesis therapy biomarkers |
| url | https://www.mdpi.com/2072-6694/13/17/4483 |
| work_keys_str_mv | AT mathildajingchow prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT yangu prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT lizhihe prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT xiaozenglin prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT yingdong prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT wenjuanmei prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT anilkapoor prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma AT damutang prognosticandtherapeuticpotentialoftheoip5networkinpapillaryrenalcellcarcinoma |