202 MTOR PATHWAY IN PAPILLARY RENAL CELL CARCINOMA (PAPRCC): PROGNOSTIC ROLE AND POTENTIAL TARGET OF THERAPY

PTP4A3 plays an important role in the tumorigenesis and metastasis of multiple tumors, but its prognostic role in renal cancer is not well understood. We utilized the Oncomine and Tumor Immunoassay Resource databases to examine the differential expression of PTP4A3 in tumor tissues and normal tissues in breast, urinary tract, gastrointestinal tract and skin. Using the GEPIA and PrognoScan databases, the independent prognostic role of PTP4A3 was confirmed in clear cell renal cell cancer and papillary renal cell cancer. Expression of PTP4A3 were obviously higher in tumor tissue compare with normal tissues (P=0.028). We haven’t found the associations of PTP4A3 and clinicopathological features in our IHC cohort. Ectopic expression of PTP4A3 promotes proliferation, migration and invasion and increased the mRNA level of TGFB1 in RCC cell lines. Immunohistochemical staining indicated that the expression of PTP4A3 associates with CD3+ (P =0.037)/CD8+ (P =0.037) intratumor TILs, not with invasive margins in renal cancer. Comprehensive analysis of immune infiltration in the TIMER database correlated PTP4A3 expression with the infiltration of B cells, CD8+ T cells, CD4+ T cells and neutrophils in both clear cell renal cell carcinoma and papillary renal cell carcinoma. PTP4A3 expression was associated with the infiltration of dendritic cells in papillary renal cell carcinoma. We further confirmed that the infiltration of B cells and CD8+ T cells was associated with poor prognosis in papillary renal cell carcinoma patients, consistent with the prognostic role of PTP4A3 in papillary renal cell carcinoma. PTP4A3 expression correlated genes involved in B cells, monocytes, M1 macrophages, Th2 and Treg cells in papillary renal cell carcinoma. These results suggest PTP4A3 as a prognostic factor with a role in regulating immune cell infiltration in papillary renal cell carcinoma.

Download Full-text

PYCR1 is associated with papillary renal cell carcinoma progression

Open Medicine ◽

10.1515/med-2019-0066 ◽

2019 ◽

Vol 14 (1) ◽

pp. 586-592 ◽

Cited By ~ 2

Author(s):

Qiu-Li Wang ◽

Ling Liu

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Expression Profiles ◽

Survival Rates ◽

Papillary Renal Cell Carcinoma ◽

Mtor Pathway ◽

Cell Counting ◽

Migration And Invasion ◽

Phosphorylated Akt

AbstractObjectiveWe aimed to determine the function of pyrroline-5-carboxylate reductase 1 (PYCR1) on progression of papillary renal cell carcinoma (PRCC) and related mechanism.MethodsThe TCGA database provided us expression profiles of PYCR1 and overall survival rates. Small interfering RNA (siRNA) was used to knockdown PYCR1; quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were conducted to identify the expression levels of mRNA and protein. The cell counting kit-8 (CCK-8) and colony formation assays were used to explore cell viability in Ketr-3 cells. The migration and invasion of Ketr-3 cells were investigated by transwell assays.ResultsWe found that PYCR1 was over-expressed in PRCC tissues and cells, causing poor outcomes. Moreover, reduction of PYCR1 played a negative role on cell proliferation, migration and invasion in tumor cells. The important Akt/mTOR pathway proteins, phosphorylated Akt (p-Akt) and phosphorylated mTOR (p-mTOR), also showed lower levels compared with control groups.ConclusionThese findings showed that disordered expression of PYCR1 could modulate PRCC progression through the Akt/mTOR pathway, implying a theoretical basis for PYCR1 as a potential therapeutic target in future clinical PRCC treatment.

Download Full-text