PARK2 and PACRG are commonly downregulated in clear‐cell renal cell carcinoma and are associated with aggressive disease and poor clinical outcome

Abstract

PARK2 is an E3 ligase, known to be involved in ubiquitination of several proteins and to play a role in neuronal protection. The gene PARK2 and its potentially co-regulated gene PACRG have been previously found to be deleted in clear-cell renal cell carcinomas (ccRCCs). The aim of our study was to evaluate the mRNA and protein expression of PARK2 and PACRG in a large cohort of ccRCC, and to investigate their association with outcome. The expression of both genes was measured by quantitative PCR in 94 primary ccRCCs and autologous nonmalignant kidney tissues. PACRG and PARK2 protein expression was determined immunohistochemically using tissue microarrays comprising 133 ccRCCs. The mRNA and protein expression of PARK2 and PACRG was significantly downregulated in ccRCCs compared with nonmalignant tissues. Low levels of PARK2 mRNA were associated with high-grade ccRCC and lymph node metastasis. Patients with low PARK2 mRNA levels showed a higher tumor-specific mortality rate and a shorter overall survival (OS) than those with high PARK2 expression. Patients without PACRG mRNA expression in the tumor had a shorter disease-free survival and OS than those with tumors expressing PACRG. In multivariate analyses, neither PARK2 nor PACRG expression were independent prognostic factors. The protein expression of PARK2 and PACRG was significantly downregulated in ccRCCs (82.8, and 96.9%, respectively), but no association with clinical outcome was noticed.

PARK2 inhibits osteosarcoma cell growth through the JAK2/STAT3/VEGF signaling pathway

“…PARK2 deletion, which leads to growth free from suppression, is uncontrolled in various cancer cell lines and promotes cancer cell proliferation in vitro 19 – 21 , 33 . Clinical studies also have shown that low PARK2 transcription correlates with increased lymph node metastasis, increased tumor grade, and worsened overall survival in malignant tumors 30 , 33 , 34 . Our study shows that PARK2 has a low expression in OS tissue and cell lines, and is associated with tumor stage.…”

Parkinson's disease‐associated protein Parkin: an unusual player in cancer

“…Metastasis is a major cause of cancer-related death. Parkin expression is significantly lower in tumors with lymph node metastases than in tumors without such metastases in the case of clear-cell renal cell carcinoma [ 56 ], pancreatic cancer and nasopharyngeal carcinoma [ 47 , 57 ]. Work from our laboratory has shown that Parkin is frequently down-regulated in breast cancer, and that lower Parkin expression correlates with worse distant metastasis-free survival [ 24 ].…”

A non-threshold region-specific method for detecting rare variants in complex diseases

“…This was consistent with previous studies [ 37 ] that reported that no significant SNPs were detected in the DN data. Among them, rs1408705 (with borderline significance, p = 0.00024) is located in PACRG (PARK2 co-regulated), which was previously found to be deleted in clear-cell renal cell carcinomas [ 38 ].…”