Decreased SLC39A1 (Solute carrier family 39 member 1) expression predicts unfavorable prognosis in patients with early-stage hepatocellular carcinoma

Abstract

Solute carrier family 39, member 1 (SLC39A1) is a member of the zinc-iron permease family and located to the cell membrane, acting as a zinc uptake transporter. However, the clinical impacts of SLC39A1 in early-stage hepatocellular carcinoma (EHCC) have not been defined. In this research, we compared the differential expression of SLC39A1 in EHCC and normal tissues based on tissue microarray, and the clinical significance of SLC39A1 in EHCC was evaluated as well. Compared with adjacent tissues, SLC39A1 was remarkably decreased in paired EHCC tissues. Besides, decreased SLC39A1 expression was significantly associated with several clinic-pathological features and serum biochemical indicators. Furthermore, Kaplan-Meier analysis exhibited that both overall survival (OS) and relapse-free survival (RFS) of patients with low expression of SLC39A1 were notably poorer than that of patients with high expression. Moreover, Cox regression analyses revealed that low expression of SLC39A1 was an independent prognostic factor for OS in patients with EHCC. Subgroup analysis also revealed beneficiary populations benefiting from the prognostic evaluation using SLC39A1 expression. Collectively, we summarized that downregulated expression of SLC39A1 is a worse prognostic factor for patients with EHCC, which can be used as a promising diagnostic and prognostic biomarker for EHCC.

Keywords: HCC; SLC39A1; biomarker; immunohistochemistry; prognosis.

Figure 1.

SLC39A1 expression in EHCC tissues and normal liver tissues. (a) Staining of SLC39A1 was evaluated by an immunoreactivity score (IRS) by multiplying the intensity score with the score of percentage of positive cells. Representative microphotographs represented low, moderate and high staining intensity in EHCC tissues and normal tissues. Brown, SLC39A1. Blue, hematoxylin. (b) SLC39A1 protein expression intensity proportion of EHCC tissues and paired normal tissues. Low expression: IRS<4; Moderate expression: 4≤ IRS<8; High expression: IRS≥8. (c) The expression of SLC39A1 protein in EHCC tissues and paired normal tissues. A significant decrease of SLC39A1 expression was observed in EHCC tissues compared with paired normal tissues

Figure 2.

Correlation between SLC39A1 expression and serum biochemical indicators levels. (a) SLC39A1 expression had potential positive correlation with ALB level. (b) SLC39A1 expression had negative correlation with AFP level. (c) SLC39A1 expression had potential positive correlation with ALL level. (d) SLC39A1 expression had no obvious correlation with TB level. ALB, albumin; AFP, alpha fetoprotein; ALT, glutamic-pyruvic transaminase; TB, total bilirubin

Figure 3.

Prognostic value of SLC39A1 expression in EHCC patients. (a) Expression of SLC39A1 in alive and dead EHCC patients. (b) Downregulated SLC39A1 expression was associated with poor OS in EHCC patients. (c) Expression of SLC39A1 in patients with our without relapse. (d) Downregulated SLC39A1 expression was associated with poor RFS in EHCC patients

Figure 4.

Subgroup analysis of the prognostic values of SLC39A1 in EHCC patients. (a) Subgroup analysis of the prognostic values for OS of SLC39A1 in EHCC patients. Downregulated SLC39A1 was correlated with OS in male patients and patients with young age, poor differentiated tumor and clinical stage 1. (b) Subgroup analysis of the prognostic values for RFS of SLC39A1 in EHCC patients. Downregulated SLC39A1 was associated with RFS in male patients and patients with young age and poor differentiated tumor