SLC39A6 参与胃腺癌的发生，且 SLC39A6 多态性 rs1050631 与切除术后的临床结局相关。

Involvement of SLC39A6 in gastric adenocarcinoma and correlation of the SLC39A6 polymorphism rs1050631 with clinical outcomes after resection.

机构信息

Department of General Surgery, Dongfang Hospital (900 Hospital of the Joint Logistics Team), 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China.

China Clinical Institute of Fuzhou General Hospital (900 Hospital of the Joint Logistics Team), Fujian Medical University, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China.

出版信息

BMC Cancer. 2019 Nov 8;19(1):1069. doi: 10.1186/s12885-019-6222-z.

DOI:10.1186/s12885-019-6222-z

PMID:31703635

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6839152/

Abstract

BACKGROUND

The single-nucleotide polymorphism SLC39A6 rs1050631 is strongly implicated in esophageal squamous cell carcinoma, leading us to question whether it may also play a role in gastric adenocarcima (GA).

METHODS

We genotyped the SLC39A6 rs1050631 in 512 patients who underwent GA resection. All study subjects lived in an area of China with high GA incidence. Genotypes were examined for possible correlation with survival and recurrence. The potential involvement of SLC39A6 in gastric cancer was explored in clinical samples and cell culture studies.

RESULTS

Multivariable analysis showed that patients with the CT + TT genotype at SLC39A6 rs1050631 were at greater risk of recurrence (hazard ratio, HR 1.387, p = 0.004) and death (HR 1.429, p = 0.002) than patients with CC genotype. Median recurrence-free and overall survival were significantly shorter in patients with the CT + TT genotype (20, 27 months) than in patients with the CC genotype (36, 43 months, p = 0.001, p < 0.001). Patients with the CT + TT genotype who were male or ≥ 60 years, or who had a tumor ≥5 cm or a moderately differentiated tumor were at significantly higher risk of recurrence and death. SLC39A6 was overexpressed in tissues from GA patients and in GA cell lines, and SLC39A6 knockdown in GA cell lines inhibited their proliferation, migration and invasion.

CONCLUSION

SLC39A6 rs1050631 correlates with post-resection prognosis of GA patients and SLC39A6 may participate in GA onset or progression.

摘要

背景

单核苷酸多态性 SLC39A6 rs1050631 强烈提示与食管鳞状细胞癌有关，这促使我们质疑其是否也与胃腺癌（GA）有关。

方法

我们对 512 名接受 GA 切除术的患者进行了 SLC39A6 rs1050631 基因分型。所有研究对象均居住在中国 GA 高发地区。检查基因型与生存和复发的可能相关性。在临床样本和细胞培养研究中探讨了 SLC39A6 参与胃癌的潜在作用。

结果

多变量分析显示，SLC39A6 rs1050631 处 CT+TT 基因型的患者复发（危险比，HR 1.387，p=0.004）和死亡（HR 1.429，p=0.002）的风险高于 CC 基因型的患者。CT+TT 基因型患者的无复发生存和总生存明显短于 CC 基因型患者（20、27 个月）（p=0.001，p<0.001）。男性或≥60 岁、肿瘤≥5cm 或中分化肿瘤的 CT+TT 基因型患者复发和死亡的风险显著更高。GA 患者组织和 GA 细胞系中 SLC39A6 表达过度，GA 细胞系中 SLC39A6 敲低抑制其增殖、迁移和侵袭。