Prognostic and Therapeutic Potential of the OIP5 Network in Papillary Renal Cell Carcinoma

Abstract

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.

OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

“…It has been reported that OIP5 induces papillary renal carcinoma cell proliferation [ 26 ]. In glioblastoma, cells exhibit obvious reduction of division when OIP5 is knocked down, whereas its recovery enhances proliferation ability [ 27 ].…”

Chromatin Separation Regulators Predict the Prognosis and Immune Microenvironment Estimation in Lung Adenocarcinoma

“…KIF18B is also illustrated to be the oncogenesis to promote tumor progression and enhance therapeutic resistance (Li B. et al, 2020;Liu et al, 2020;Jiang J. et al, 2021). OIP5 upregulation is observed in human cancers (Chow et al, 2021), and seems to be linked to drug resistance (Rodrigues-Junior et al, 2018). NUF2 is found to be a prognostic biomarker and therapeutic target which is correlated with the immune infiltration in patients with cancer Shan et al, 2021;Xie et al, 2021).…”

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

“…Chow et al [6] have analyzed the role of OPA interacting protein 5 (OIP5) in 20 papillary renal cell carcinomas (PRCC) and 37 (CCRCC). OIP5 up-regulation has been associated with biological aggressiveness in a broad spectrum of malignant neoplasms, PRCC included.…”