Overexpression of SLC7A11: a novel oncogene and an indicator of unfavorable prognosis for liver carcinoma
Abstract
Aim: SLC7A11 is a gene that encodes a cystine–glutamate antiporter, which has been detected to be overexpressed in various cancers. Thus, we aimed to validate its expression and clinical significance in liver cancer. Methods: Bioinformatic analysis was conducted and a tissue microarray was utilized for detecting SLC7A11 expression in liver cancer tissues by immunohistochemistry assay. Results: High expressions of SLC7A11 have no association with clinical parameters such as age, sex and clinical stages, except for advanced pathological stages. Cox regression analysis revealed that SLC7A11 might be an independent prognostic factor for liver cancer patients. Conclusion: SLC7A11 overexpression might be a novel biomarker and a potential unfavorable prognostic factor as well as a potential therapeutic target for liver carcinoma.
References
- 1 . Histopathology of hepatocellular carcinoma. World J. Gastroenterol. 20(43), 15955–15964 (2014).
- 2 . Causes of and prevention strategies for hepatocellular carcinoma. Semin. Oncol. 39(4), 374–383 (2012).
- 3 . Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma. Acta Pharm. Sin. B 6(5), 426–429 (2016).
- 4 Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans. Br. J. Cancer 116(5), 688–696 (2017).
- 5 Dietary trace element intake and liver cancer risk: results from two population-based cohorts in China. Int. J. Cancer 140(5), 1050–1059 (2017).
- 6 Cadmium exposure and cancer mortality in a prospective cohort: the strong heart study. Environ. Health Perspect. 122(4), 363–370 (2014).
- 7 Cadmium, organ toxicity and therapeutic approaches. A review on brain, kidney and testis damage. Curr. Med. Chem. 24(35), 3879–3893 (2017).
- 8 Noninfective occupational risk factors for hepatocellular carcinoma: a review (review). Mol. Med. Rep. 15(2), 511–533 (2017).
- 9 . Identification and characterization of cadmium-related genes in liver carcinoma. Biol. Trace Elem. Res. 182(2), 238–247 (2017).
- 10 The GeneCards suite: from gene data mining to disease genome sequence analyses. Curr. Protoc. Bioinformatics 54, 1.30.1–1.30.33 (2016).
- 11 Senescence marker protein 30 (SMP30) serves as a potential prognostic indicator in hepatocellular carcinoma. Sci. Rep. 6, 39376 (2016).
- 12 . Excitotoxic SLC7A11 expression is a marker of poor glioblastoma survival and a potential therapeutic target. Neurosurgery 77(6), N16–N17 (2015).
- 13 . MiR-375/SLC7A11 axis regulates oral squamous cell carcinoma proliferation and invasion. Cancer Med. 6(7), 1686–1697 (2017).
- 14 Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer. Br. J. Cancer 110(10), 2506–2513 (2014).
- 15 Cystine/glutamic acid transporter is a novel marker for predicting poor survival in patients with hepatocellular carcinoma. Oncol. Rep. 29(2), 685–689 (2013).
- 16 . Increased expression of system xc- in glioblastoma confers an altered metabolic state and temozolomide resistance. Mol. Cancer Res. 14(12), 1229–1242 (2016).
- 17 . SLC7A11 overexpression in glioblastoma is associated with increased cancer stem cell-like properties. Stem Cells Dev. 26(17), 1236–1246 (2017).
- 18 Reduced expression of miRNA-27a modulates cisplatin resistance in bladder cancer by targeting the cystine/glutamate exchanger SLC7A11. Clin. Cancer Res. 20(7), 1990–2000 (2014).
- 19 Xc- inhibitor sulfasalazine sensitizes colorectal cancer to cisplatin by a GSH-dependent mechanism. Cancer Lett. 368(1), 88–96 (2015).
- 20 . Induction of ferroptotic cell death for overcoming cisplatin resistance of head and neck cancer. Cancer Lett. 381(1), 96–103 (2016).
- 21 Drug repurposing: sulfasalazine sensitizes gliomas to Gamma Knife radiosurgery by blocking cystine uptake through system xc-, leading to glutathione depletion. Oncogene 34(49), 5951–5959 (2015).
- 22 Ferroptosis: process and function. Cell Death Differ. 23(3), 369–379 (2016).
- 23 Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520(7545), 57–62 (2015).
- 24 . CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells. Front. Cell Dev. Biol. 5, 18 (2017).
- 25 Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia. Cancer Sci. 104(10), 1323–1329 (2013).
- 26 CD147 as a novel prognostic biomarker for hepatocellular carcinoma: a meta-analysis. Biomed. Res. Int. 2017, 5019367 (2017).
- 27 . CD147: regulator of hyaluronan signaling in invasiveness and chemoresistance. Adv. Cancer Res. 123, 351–373 (2014).
- 28 . Cystine-glutamate transporter SLC7A11 in cancer chemosensitivity and chemoresistance. Cancer Res. 65(16), 7446–7454 (2005).
- 29 Disruption of xCT inhibits cell growth via the ROS/autophagy pathway in hepatocellular carcinoma. Cancer Lett. 312(1), 55–61 (2011).