Kim Kyoung Min, Hussein Usama Khamis, Bae Jun Sang, Park See-Hyoung, Kwon Keun Sang, Ha Sang Hoon, Park Ho Sung, Lee Ho, Chung Myoung Ja, Moon Woo Sung, Kang Myoung Jae, Jang Kyu Yun
Department of Pathology, Chonbuk National University Medical School, Jeonju, South Korea.
Research Institute of Clinical Medicine of Chonbuk National University, Jeonju, South Korea.
Front Oncol. 2019 Jan 22;9:14. doi: 10.3389/fonc.2019.00014. eCollection 2019.
FAM83H is primarily known for its role in amelogenesis; however, recent reports suggest FAM83H might be involved in tumorigenesis. Although the studies of FAM83H in kidney cancer are limited, a search of the public database shows a significant association between FAM83H and pannexin-2 (PANX2) in clear cell renal cell carcinomas (CCRCCs). Therefore, we evaluated the clinicopathological significance of the immunohistochemical expression of FAM83H and PANX2 in 199 CCRCC patients. The expression of FAM83H and PANX2 were significantly associated with each other. In univariate analysis, individual, and co-expression pattern of FAM83H and PANX2 was significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients: nuclear expression of FAM83H (OS; < 0.001, RFS; < 0.001), cytoplasmic expression of FAM83H (OS; < 0.001, RFS; < 0.001), nuclear expression of PANX2 (OS; < 0.001, RFS; < 0.001), cytoplasmic expression of PANX2 (OS; < 0.001, RFS; < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; < 0.001, RFS; < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; < 0.001, RFS; = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; < 0.001, RFS; < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS ( = 0.030) in multivariate analysis. In Caki-1 and Caki-2 CCRCC cells, knock-down of FAM83H decreased PANX2 expression and cell proliferation, and overexpression of FAM83H increased PANX2 expression and cell proliferation. These results suggest that FAM83H and PANX2 might be involved in the progression of CCRCC in a co-operative manner, and their expression might be used as novel prognostic indicators for CCRCC patients.
FAM83H主要因其在釉质形成中的作用而为人所知；然而，最近的报告表明FAM83H可能参与肿瘤发生。尽管关于FAM83H在肾癌中的研究有限，但对公共数据库的搜索显示，在透明细胞肾细胞癌（CCRCC）中，FAM83H与泛连接蛋白2（PANX2）之间存在显著关联。因此，我们评估了199例CCRCC患者中FAM83H和PANX2免疫组化表达的临床病理意义。FAM83H和PANX2的表达彼此显著相关。在单变量分析中，FAM83H和PANX2的单独及共表达模式与CCRCC患者较短的总生存期（OS）和无复发生存期（RFS）显著相关：FAM83H的核表达（OS；<0.001，RFS；<0.001）、FAM83H的胞质表达（OS；<0.001，RFS；<0.001）、PANX2的核表达（OS；<0.001，RFS；<0.001）、PANX2的胞质表达（OS；<0.001，RFS；<0.001）、核FAM83H和核PANX2的共表达模式（OS；<0.001，RFS；<0.001）。在多变量分析中，FAM83H的核表达（OS；<0.001，RFS；=0.003）以及核FAM83H和PANX2的共表达模式（OS；<0.001，RFS；<0.001）是CCRCC患者较短生存期的独立指标。在多变量分析中，FAM83H的胞质表达与较短的RFS相关（=0.030）。在Caki-1和Caki-2 CCRCC细胞中，敲低FAM83H可降低PANX2表达和细胞增殖，而FAM83H的过表达则增加PANX2表达和细胞增殖。这些结果表明，FAM83H和PANX2可能以协同方式参与CCRCC的进展，它们的表达可能作为CCRCC患者新的预后指标。
