High Expression of SQSTM1/p62 Protein Is Associated with Poor Prognosis in Epithelial Ovarian Cancer

被引:44
作者
Iwadate, Reiko [1 ,2 ,3 ]
Inoue, Jun [1 ,2 ,4 ]
Tsuda, Hitoshi [5 ]
Takano, Masashi [6 ]
Furuya, Kenichi [6 ]
Hirasawa, Akira [3 ]
Aoki, Daisuke [3 ]
Inazawa, Johji [1 ,2 ,4 ,7 ]
机构
[1] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Cytogenet, Tokyo 1138510, Japan
[2] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Tokyo 1138510, Japan
[3] Keio Univ, Sch Med, Dept Obstet & Gynecol, Tokyo 160, Japan
[4] Tokyo Med & Dent Univ, Bioresource Res Ctr, Tokyo 1138510, Japan
[5] Natl Def Med Coll, Dept Pathol, Saitama, Japan
[6] Natl Def Med Coll, Dept Obstet & Gynecol, Tokyo, Japan
[7] Tokyo Med & Dent Univ, Hard Tissue Genome Res Ctr, Dept Genome Med, Tokyo 1138510, Japan
基金
日本学术振兴会;
关键词
epithelial ovarian cancer; serous carcinoma; immunohistochemistry; p62; prognosis; ANTIOXIDANT RESPONSE ELEMENT; AUTOPHAGY; P62/SQSTM1; P62; NRF2; DEGRADATION; ACTIVATION; MECHANISM; CARCINOMA; TARGET;
D O I
10.1267/ahc.14048
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
High expression of SQSTM1/p62 (p62) protein, which functions as a hub for various cellular signaling pathways, has been detected in several human cancers. However, the clinicopathological impact of high p62 expression is largely unknown in epithelial ovarian cancer (EOC). Here, the expression level of p62 in primary EOCs (n=266) was assessed by immunohistochemistry, and its clinical significance was analyzed. Univariate and multivariate analyses were used to determine the impact of p62 expression on overall survival. p62 was expressed in the cytoplasm (Cyto) and/or nucleus (Nuc) in primary E0Cs, and an expression subtype (Cyto(High)/Nuc(Low)), showing high expression in the cytoplasm but low expression in the nucleus, was significantly correlated with serous carcinoma (P<0.001), advanced stage (P=0.005), presence of residual tumor (P<0.001), and low overall survival rate (P=0.013). Furthermore, in serous carcinomas (n=107), the p62 Cyto(High)/Nuc(Low) subtype was significantly correlated with low overall survival rate (P=0.019) as an independent factor (P=0.044). Thus, our findings suggest that high expression of cytoplasmic p62 may be a novel prognostic biomarker in EOC, particularly in serous carcinoma.
引用
收藏
页码:295 / 301
页数:7
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