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Cancer:有助更好预测前列腺癌预后的生物标志物LRPPRC

来源:生物谷 2014-02-18 21:27

2014年2月18日讯 /生物谷BIOON/--近日,得克萨斯州A&M健康科学中心生物科学与技术(TAMHSC)研究所研究人员确定了一种新生物标志物将更准确地预测前列腺癌患者的预后,这一发现可能进一步影响抗癌药物的开发,并最终预防癌症。

这项研究关注自噬概念,也即细胞中控制自我消化的过程,在自噬过程中,细胞废物被“包装”和“运输”进入“溶酶体”细胞器,然后被降解和回收。这个过程缺陷会导致细胞废物积累,以及可能最终导致肿瘤的形成。

在以前的研究中研究人员Liu发现蛋白质LRPPRC能抑制细胞自噬和维持线粒体的活性。最新的研究表明LRPPRC蛋白水平与肿瘤分级、肿瘤分期和前列腺特异性抗原(PSA)水平呈正相关关系,以及与患者响应激素疗法和总生存期呈负相关。

有更高水平LRPPRC的肿瘤细胞自噬活性水平会较低,因而细胞废物将不会被有效清理。这些肿瘤细胞恶性程度会更高,导致预后不良,如果前列腺癌患者LRPPRC蛋白质低水平,那么生存时间比那些携带高水平LRPPRC的患者更长。

该研究不仅促进LRPPRC蛋白水平发展作为一个独立的标记物预测前列腺癌患者预后,而且还提示LRPPRC调节自噬作为抗癌药物和癌症预防的新作用靶点。最终,研究旨在开发一种治疗方法,以减少LRPPRC水平,从而帮助前列腺癌患者活得更长。(生物谷Bioon.com)

 

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

Xianhan Jiang MD, et al.

BACKGROUND
Autophagy has recently been found to play important roles in tumorigenesis and leucine-rich pentatricopeptide repeat motif-containing protein (LRPPRC) has been identified as an inhibitor that suppresses autophagy and mitophagy and maintains mitochondrial activity. The authors hypothesized that LRPPRC levels can be used as a biomarker for the diagnosis and prognosis of prostate cancer.

METHODS
Immunochemistry analysis was performed to evaluate the levels of LRPPRC in 112 samples collected from patients with prostate adenocarcinoma (PCa) and 38 samples from patients with benign prostatic hyperplasia (BPH) who were enrolled in hospitals in Guangzhou City, China and were followed for 10 years.

RESULTS
Significantly higher levels of LRPPRC were found in PCa samples compared with BPH samples. Greater than 75% of patients with PCa demonstrated high levels of LRPPRC whereas only 10% of patients with BPH were found to have similar levels of LRPPRC. The levels of LRPPRC were found to be positively correlated with tumor grade, metastasis, and serum prostate-specific antigen level, but were negatively correlated with hormone therapy sensitivity after 2 years of surgery and overall survival. The association between high levels of LRPPRC and late-stage PCa or hormone therapy insensitivity was confirmed in tissue samples collected from prostate-specific phosphatase and tensin homolog (PTEN)-/- mice or hormone-dependent and hormone-independent PCa cell lines.

CONCLUSIONS
LRPPRC levels may be used as an independent biomarker for patients with PCa at a late stage with poor prognosis.

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