Expression and Clinical Implication of Autophagy-Associated Protein p62 in Osteosarcoma

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusion: Our results suggest that p62 may be an effective predictor of prognosis and a potential target for therapy in osteosarcoma.

p62/SQSTM1 – steering the cell through health and disease

“…Currently, the protein is a diagnostic and prognostic marker in multiple forms of cancer, i.e. osteosarcoma, oral squamous cell carcinoma, cutaneous malignant melanoma, esophageal adenocarcinoma, ovarian, colon, breast and non-small cell lung cancers, and solid tumors Daniels et al, 2013;Ellis et al, 2014;Giatromanolaki et al, 2014;Inoue et al, 2012;Iwadate et al, 2014;Liu et al, 2014a;Luo et al, 2013;Ma et al, 2018;Niklaus et al, 2017;Park et al, 2013;Ruan et al, 2018;Schläfli et al, 2016), and has attracted attention as a potential therapeutic target (Yan et al, 2017;Zhang et al, 2016). An antitumor SQSTM1 DNA vaccine has already been developed and trialed in humans (Gabai et al, 2014;Ponomarenko et al, 2017;Sabbieti et al, 2015;Venanzi et al, 2013); however, SQSTM1 can have both beneficial and deleterious effects depending on the pathological context, as is the case for autophagy itself (Dikic and Elazar, 2018).…”

Targeting autophagy is a promising therapeutic strategy to overcome chemoresistance and reduce metastasis in osteosarcoma

“…Lu et al (80) demonstrated that p62 was detected in 54/70 OS samples (77.1%), and that its overexpression was associated with tumor size, metastasis, clinical stage and poor prognosis. Conversely, Ma et al (81) discovered that the 5-year survival rate of patients with OS with low p62 expression was lower than that of patients with high p62 expression, suggesting that decreased p62 expression was associated with higher metastasis and chemotherapy resistance rates in OS.…”

Study on autophagy-related biomarkers in pancreatic cancer based on bioinformatics

“…It has a poor prognosis because of its challenging early diagnosis. Autophagy is a conserved intracellular degradation/recycling process in all eukaryotes, which can cause cancer cell regression by stimulating or inhibiting autophagy [27]. By studying autophagy genes associated with PC, this study seeks biomarkers of PC and promotes the study of PC-related mechanisms and early diagnosis.…”