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

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. Keywords: SLC39A6 rs1050631, Gastric adenocarcinoma, Prognostic biomarker, High-occurrence area, Ki67, TOPOII

Zinc transporter LIV1: A promising cell surface target for triple negative breast cancer

“…expression was observed in a number of cancers including pancreas (Unno et al, 2009(Unno et al, , 2014, prostate (L. Cao, 2012;Lue et al, 2011;Yamashita et al, 2004), liver (Lian et al, 2016;Shen et al, 2013), melanoma, breast, ovary (Ma et al, 2009(Ma et al, , 2015, cervical (Chen et al, 2019;Lue et al, 2011;Zhao et al, 2007), uterine, esophageal carcinoma (Cheng et al, 2017;Wu et al, 2013), gastric (J. Gao et al, 2019) and lung carcinoma (Sussman et al, 2014;Wan et al, 2018).…”

“…In pre‐clinical models, LIV1 expression was found to be associated with epithelial‐to‐mesenchymal transition—in embryonic development, cancer promotion, and progression (GeneMANIA, 2021). LIV1 expression was observed in a number of cancers including pancreas (Unno et al, 2009, 2014), prostate (L. Cao, 2012; Lue et al, 2011; Yamashita et al, 2004), liver (Lian et al, 2016; Shen et al, 2013), melanoma, breast, ovary (Ma et al, 2009, 2015), cervical (Chen et al, 2019; Lue et al, 2011; Zhao et al, 2007), uterine, esophageal carcinoma (Cheng et al, 2017; Wu et al, 2013), gastric (J. Gao et al, 2019) and lung carcinoma (Sussman et al, 2014; Wan et al, 2018).…”

Toward unzipping the ZIP metal transporters: structure, evolution, and implications on drug discovery against cancer

“…was initially identified to be an oestrogen-responsive factor upregulated in breast cancer tissues and a biomarker of this cancer [113][114][115][116][117]. Upregulated ZIP6 was also reported in many other types of cancer cells, including prostate cancer [118], pancreatic cancer [119], hepatocellular carcinoma [120], esophageal squamous-cell carcinoma [121], gastric adenocarcinoma [122], and colorectal cancer [123]. ZIP6 and ZIP10 form a heteromer essential for cell proliferation [73,124] and ZIP10 by itself has also been implicated in cancers [125,126].…”

Honokiol Suppression of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Gastric Cancer Cell Biological Activity and Its Mechanism

“…Preoperative neoadjuvant therapy, perioperative chemotherapy, and postoperative adjuvant chemoradiotherapy can reduce the recurrence rate and improve the disease-free survival of patients. Clinical trials have demonstrated that preoperative neoadjuvant therapy can significantly improve the 5-year survival rate of patients and improve the radical resection rate and the efficacy of surgical treatment in patients with advanced gastric cancer [ 3 – 8 ]. Research on tumor pathogenesis has suggested that the occurrence and metastasis of gastric cancer are related to the overexpression of some specific oncogenes or receptor genes [ 9 ].…”