Elevated levels of mitochondrion‐associated autophagy inhibitor LRPPRC are associated with poor prognosis in patients with prostate cancer

Abstract

BACKGROUND Autophagy has recently been found to play important roles in tumorigenesis and LRPPRC has been identified as an inhibitor that suppresses autophagy and mitophagy and maintains mitochondrial activity. We hypothesized that LRPPRC levels can be used as a biomarker for diagnosis and prognosis of prostate cancer. METHODS We performed immunochemistry analysis to evaluate the levels of LRPPRC in 112 samples collected from patients with prostate adenocarcinomas (PCa) and 38 samples from patients with benign prostate hyperplasia (BPH) enrolled in hospitals in Guangzhou city of China that have been followed up for 10 years. RESULTS We found that there were significant higher levels of LRPPRC in PCa than in BPH. More than three quarters of PCa patients showed high levels of LRPPRC while only 10% of BPH patients had similar levels of LRPPRC. The levels of LRPPRC protein were positively correlated with tumor grade, metastasis and serum PSA, but negatively correlated with hormone therapy sensitivity after 2 years of surgery and overall survival. The association of high levels of LRPPRC with late stage of PCa or hormone therapy insensitivity was confirmed in tissue samples collected from prostate-specific PTEN−/− mice or hormone-dependent and independent prostate cancer cell lines. CONCLUSION The levels of LRPPRC may be used as an independent biomarker for PCa patients at late-stage with poor prognosis.

Elevated levels of autophagy-related marker ULK1 and mitochondrion-associated autophagy inhibitor LRPPRC are associated with biochemical progression and overall survival after androgen deprivation therapy in patients with metastatic prostate cancer

“…In our study, PCa tissue from the majority of patients was obtained by biopsy, which was similar to the situation in some other studies 18 19…”

Defects in MAP1S‐mediated autophagy cause reduction in mouse lifespans especially when fibronectin is overexpressed

“…The SAS software was used for all statistical analyses, and a P value of <0.05 was considered significant. All statistical analyses were carried out similarly as previously described (Jiang et al ., 2014). …”

“…Oxidative stress in turn activates NLRP3 inflammasome and eventually induces an inflammatory form of cell death referred to as pyroptosis that promotes the mortality and impair the survival of host structural, hematopoietic, and immune‐competent cells (Lamkanfi & Dixit, 2014; Ryter et al ., 2014; Terlizzi et al ., 2014; Yu et al ., 2014). Cancer patients with defective autophagy live a short lifespans (Jiang et al ., 2014, 2015). Both calorie restriction and pharmacologic agents that mimic the impact of calorie restriction induce autophagy and prolong lifespans (Madeo et al ., 2015).…”

Expression Profile of Autophagy-related Markers in Localized Prostate Cancer: Correlation With Biochemical Recurrence After Radical Prostatectomy

“…[10][11][12][13][14] In the field of PC research as well, a few studies assessed the significance of molecular markers involved in autophagy. [15][16][17] For example, Giatromanolaki et al 17 reported that the strong and extensive expression of LC3 in PC specimens was closely associated with the Gleason score, whereas Jiang et al 16 showed the significant impact of the elevated expression of a mitochondrion-associated autophagy inhibitor, leucine-rich pentatricopeptide repeat motifecontaining protein, on the prognosis of PC patients at a late stage with a poor prognosis. To our knowledge, however, there have not been any studies investigating the prognostic impact of molecular markers involved in the autophagic pathway for men with early stage PC.…”

“…8,9 In recent years, there have been several studies reporting that the expression profiles of molecular markers consisting of the autophagy pathway could be used as useful predictors of clinical courses in several types of human malignant tumor [10][11][12][13][14] ; however, limited information is available on the prognostic significance of autophagy-related proteins in patients with PC. [15][16][17] Considering these findings, we evaluated the expression patterns of multiple autophagy-related proteins, including autophagy-related gene 5 (Atg5), autophagyrelated gene 9 (Atg9), Beclin1, microtubule-associated protein light chain 3 (LC3), and UNC-51elike kinase 1 (ULK1), in RP specimens from 160 patients with localized PC to analyze the prognostic significance of these markers in this cohort of patients.…”