Department of Orthopaedics, Panyu Hospital of Chinese Medicine, Guangzhou, China.
Department of Orthopaedic Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Oncology. 2018;95(1):52-60. doi: 10.1159/000487437. Epub 2018 Apr 4.
Recent studies highlight the role of autophagy in cancer tumorigenesis, recurrence, metastasis, and chemoresistance. p62 is an adapter protein that is crucial for the autophagy pathway. In this study, we will describe the expression of p62 and its correlation with clinic prognosis in osteosarcoma.
Western blot was used to test the expression of p62 in osteosarcoma cell lines (U2OS, KHOS, MG63, Saos-2, U2OSR2, KHOSR2, and 143B). A tissue microarray (TMA) was analyzed by immunohistochemistry to determine the expression levels of p62 in osteosarcoma patients and evaluate any correlation between p62 and clinical characteristics in osteosarcoma patients.
p62 was expressed differently in all cell lines. The TMA also showed differential expression in osteosarcoma tissues. Seventy-five of 79 (94.9%) patient tissues exhibited p62 immunostaining, ranging from no staining (4 of 97, 5.1%) to 1+ staining (40 of 79, 50.6%), 2+ staining (17 of 79, 21.5%), and 3+ staining (18 of 79, 22.8%). The low staining (1+) was classified as the p62 weak group (50.6%), the medium staining (2+) and intense staining (3+) were classified as the p62 strong group (44.3%). Analyzing the clinical data of the osteosarcoma TMA, we found that the 5-year survival rate of patients with weak p62 expression was significantly lower than that of the patients with strong p62 expression (p = 0.0165). Furthermore, the decreased p62 expression may be associated with higher metastatic and chemoresistant rates in osteosarcoma patients.
Our results suggest that p62 may be an effective predictor of prognosis and a potential target for therapy in osteosarcoma.
最近的研究强调了自噬在癌症肿瘤发生、复发、转移和化疗耐药中的作用。p62 是一种衔接蛋白，对自噬途径至关重要。在本研究中，我们将描述 p62 在骨肉瘤中的表达及其与临床预后的相关性。
采用 Western blot 检测骨肉瘤细胞系（U2OS、KHOS、MG63、Saos-2、U2OSR2、KHOSR2 和 143B）中 p62 的表达。采用组织微阵列（TMA）免疫组织化学法检测骨肉瘤患者中 p62 的表达水平，并评估 p62 与骨肉瘤患者临床特征之间的相关性。
p62 在所有细胞系中的表达均不同。TMA 也显示骨肉瘤组织中存在差异表达。75 例 79 例（94.9%）患者组织存在 p62 免疫染色，从无染色（4/97，5.1%）到 1+染色（40/79，50.6%）、2+染色（17/79，21.5%）和 3+染色（18/79，22.8%）。低染色（1+）被归类为 p62 弱组（50.6%），中染色（2+）和强染色（3+）被归类为 p62 强组（44.3%）。分析骨肉瘤 TMA 的临床资料发现，p62 表达较弱的患者 5 年生存率明显低于 p62 表达较强的患者（p=0.0165）。此外，p62 表达降低可能与骨肉瘤患者转移率和化疗耐药率较高有关。
我们的结果表明，p62 可能是骨肉瘤预后的有效预测因子，也是治疗的潜在靶点。
