Abstract
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; P < 0.001, RFS; P < 0.001), cytoplasmic expression of FAM83H (OS; P < 0.001, RFS; P < 0.001), nuclear expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), cytoplasmic expression of PANX2 (OS; P < 0.001, RFS; P < 0.001), co-expression pattern of nuclear FAM83H and nuclear PANX2 (OS; P < 0.001, RFS; P < 0.001). In multivariate analysis, nuclear expression of FAM83H (OS; P < 0.001, RFS; P = 0.003) and the co-expression pattern of nuclear FAM83H and PANX2 (OS; P < 0.001, RFS; P < 0.001) were independent indicators of shorter survival of CCRCC patients. Cytoplasmic expression of FAM83H was associated with shorter RFS (P = 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.
Highlights
With sequence similarity 83 H (FAM83H) is one of the eight FAM83 family members, from FAM83A to Family with sequence similarity 83 H (FAM83H) [1, 2]
This study investigated the expression and clinical significance of FAM83H and PANX2 expressions in clear cell renal cell carcinomas (CCRCCs) and showed that the expression patterns of FAM83H and PANX2 were significantly associated with advanced clinicopathologic factors of CCRCC such as tumor size and tumor stage
There was a significant association between FAM83H expression and PANX2 expression and the expression patterns of both were significantly associated with shorter overall survival (OS) and relapse-free survival (RFS) of CCRCC patients
Summary
With sequence similarity 83 H (FAM83H) is one of the eight FAM83 family members, from FAM83A to FAM83H [1, 2]. According to the type of FAM83, diverse roles for members of FAM83 family have been reported [1, 2]. The expression of FAM83H was transcriptionally controlled by the oncogene MYC and associated with proliferation and invasiveness of liver cancer cells [6]. The expression of FAM83H was an independent indicator of poor prognosis of hepatocellular carcinoma patients [6] and higher expression of FAM83H was associated with shorter disease-free survival of uterine cancer [1]. Among the eight FAM83 family members, the expression of FAM83D and FAM83H was consistently higher in tumors in various human tissue types, with up-regulation of FAM83D observed in 78% of tumors (21 of 27 data sets) and up-regulation of FAM83H observed in 59% of tumors (16 of 27 data sets) [1]. Since the role of FAM83H in tumorigenesis might differ according to the type of tissue or cancer, further study is needed to clarify its role
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