We use cookies to improve your experience. By continuing to browse this site, you accept our cookie policy.×
Skip main navigation
Aging Health
Bioelectronics in Medicine
Biomarkers in Medicine
Breast Cancer Management
CNS Oncology
Colorectal Cancer
Concussion
Epigenomics
Future Cardiology
Future Medicine AI
Future Microbiology
Future Neurology
Future Oncology
Future Rare Diseases
Future Virology
Hepatic Oncology
HIV Therapy
Immunotherapy
International Journal of Endocrine Oncology
International Journal of Hematologic Oncology
Journal of 3D Printing in Medicine
Lung Cancer Management
Melanoma Management
Nanomedicine
Neurodegenerative Disease Management
Pain Management
Pediatric Health
Personalized Medicine
Pharmacogenomics
Regenerative Medicine
Research Article

Eight-gene prognostic signature associated with hypoxia and ferroptosis for gastric cancer with general applicability

    Junyu Huo

    Liver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266003, China

    Qingdao University, No. 308 Ningxia Road, Qingdao 266071, China.

    ,
    Liqun Wu

    *Author for correspondence:

    E-mail Address: wulq5810@126.com

    Liver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266003, China

    &
    Yunjin Zang

    Liver Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266003, China

    Published Online:https://doi.org/10.2217/epi-2020-0411

    Aims: To investigate the prognostic significance of hypoxia- and ferroptosis-related genes for gastric cancer (GC). Materials & methods: We extracted data on 259 hypoxia- and ferroptosis-related genes from The Cancer Genome Atlas and identified the differentially expressed genes between normal (n = 32) and tumor (n = 375) tissues. A risk score was established by univariate Cox regression analysis and LASSO penalized Cox regression analysis. Results: The risk score contained eight genes showed good performance in predicting overall survival and relapse-free survival in GC patients in both the training cohort (The Cancer Genome Atlas, n = 350) and the testing cohorts (GSE84437, n = 431; GSE62254, n = 300; GSE15459, n = 191; GSE26253, n = 432). Conclusion: The eight-gene signature may help to the improve the prognostic risk classification of GC.

    Papers of special note have been highlighted as: •• of considerable interest

    References

    • 1. Thrift AP, El-Serag HB. Burden of gastric cancer. Clin. Gastroenterol. Hepatol. 18(3), 534–542 (2020). •• Proposed the challenges that human beings need to face in conquering gastric cancer.
    • 2. Patel TH, Cecchini M. Targeted therapies in advanced gastric cancer. Curr. Treat. Options Oncol. 21(9), 1–14 (2020). •• Summarized the the latest progress of treatment strategies for gastric cancer.
    • 3. Eusebi LH, Telese A, Marasco G, Bazzoli F, Zagari RM Gastric cancer prevention strategies: a global perspective. J. Gastroenterol. Hepatol. 35, 1495–1502 (2020).
    • 4. Sa JK, Hong JY, Lee I-K et al. Comprehensive pharmacogenomic characterization of gastric cancer. Genome Med. 12(1), 1–12 (2020).
    • 5. Sexton RE, Al Hallak MN, Diab M, Azmi ASJC, Reviews M. Gastric cancer: a comprehensive review of current and future treatment strategies. 39(4), 1179–1203 (2020).
    • 6. Dixon SJ, Lemberg KM, Lamprecht MR et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5), 1060–1072 (2012).
    • 7. Stockwell BR, Angeli JPF, Bayir H et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171(2), 273–285 (2017).
    • 8. Xie Y, Hou W, Song X et al. Ferroptosis: process and function. Cell Death Differ. 23(3), 369–379 (2016).
    • 9. Silva VL. Exploiting the cancer niche: tumor-associated macrophages and hypoxia as promising synergistic targets for nano-based therapy. J. Control. Release 253, 82–96 (2017).
    • 10. Huang Y, Lin D, Taniguchi CM. Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe? Sci. China Life Sci. 60(10), 1114–1124 (2017).
    • 11. Stoeltzing O, McCarty MF, Wey JS et al. Role of hypoxia-inducible factor 1α in gastric cancer cell growth, angiogenesis, and vessel maturation. J. Natl Cancer Inst. 96(12), 946–956 (2004).
    • 12. Danza K, Silvestris N, Simone G et al. Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance. Cancer Biol. Ther. 17(4), 400–406 (2016).
    • 13. Shi W-J, Gao J-B. Molecular mechanisms of chemoresistance in gastric cancer. World J. Gastrointest. Oncol. 8(9), 673 (2016).
    • 14. Verma HK, Falco G, Bhaskar L. Molecular signaling pathways involved in gastric cancer chemoresistance. In: Theranostics Approaches to Gastric and Colon Cancer. Springer, 117–134 (2020).
    • 15. Sinha A, Huang V, Livingstone J et al. The proteogenomic landscape of curable prostate cancer. Cancer Cell 35(3), 414–427.e416 (2019).
    • 16. Bailey ST, Smith AM, Kardos J et al. MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma. Nat. Commun. 8(1), 1–12 (2017).
    • 17. Huo J, Wu L, Zang Y. Development and validation of a novel immune–gene pairs prognostic model associated with CTNNB1 alteration in hepatocellular carcinoma. Med. Sci. Monit. 26, e925494–e925494 (2020).
    • 18. Huo J, Wu L, Zang Y. A robust nine-gene prognostic signature associated with tumour doubling time for hepatocellular carcinoma. Life Sci. 260, 118396–118396 (2020).
    • 19. Charoentong P, Finotello F, Angelova M et al. Pan-cancer immunogenomic analyses reveal genotype–immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18(1), 248–262 (2017).
    • 20. Newman AM, Liu CL, Green MR et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12(5), 453–457 (2015).
    • 21. Serra O, Galán M, Ginesta M, Calvo M, Sala N, Salazar R. Comparison and applicability of molecular classifications for gastric cancer. Cancer Treat Rev. 77, 29–34 (2019).
    • 22. Sano T, Coit DG, Kim HH et al. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer 20(2), 217–225 (2017).
    • 23. Godet I, Shin YJ, Ju JA, Ye IC, Wang G, Gilkes DM. Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nat. Commun. 10(1), 1–18 (2019).
    • 24. Yoshihara K, Shahmoradgoli M, Martínez E et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat. Commun. 4(1), 1–11 (2013). •• Described how to estimate tumor purity by analyzing the specific gene expression characteristics of immune and stromal cells.
    • 25. Bezdenezhnykh N, Semesiuk N, Lykhova O, Zhylchuk V, Kudryavets Y. Impact of stromal cell components of tumor microenvironment on epithelial-mesenchymal transition in breast cancer cells. Exp. Oncol. 36, 72–78 (2014).
    • 26. Chen B, Khodadoust MS, Liu CL, Newman AM, Alizadeh AA. Profiling tumor infiltrating immune cells with CIBERSORT. In: Cancer Systems Biology. Springer, 243–259 (2018). •• Described how to quantify immune cell infiltration in tumor tissues with standardized gene presentation data.
    • 27. Zhang J, Piao H-Y, Guo S et al. LINC00163 inhibits the invasion and metastasis of gastric cancer cells as a ceRNA by sponging miR-183 to regulate the expression of AKAP12. 25(4), 1–14 (2020).
    • 28. Teng F, Xu Z, Chen J et al. DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncol. Rep. 40(3), 1203–1222 (2018).
    • 29. Gong W, Qie S, Huang P, Xi J. Deletion of long noncoding RNA EFNA3 aggravates hypoxia-induced injury in PC-12 cells by upregulation of miR-101a. J. Cell Biochem. 120(1), 836–847 (2019).
    • 30. Ren K, Liu Q, An Z, Zhang D, Chen X. MiR-144 functions as tumor suppressor by targeting PIM1 in gastric cancer. Eur. Rev. Med. Pharmacol. Sci. 21(13), 3028 (2017).
    • 31. Wang Y, Qi Z, Zhou M et al. Stanniocalcin-1 promotes cell proliferation, chemoresistance and metastasis in hypoxic gastric cancer cells via Bcl-2. Oncol. Rep. 41(3), 1998–2008 (2019).
    • 32. Moore MJ, Blachere NE, Fak JJ et al. ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity. Elife 7, e33057 (2018).
    • 33. Xu B, Bai Z, Yin J, Zhang Z. Global transcriptomic analysis identifies SERPINE1 as a prognostic biomarker associated with epithelial-to-mesenchymal transition in gastric cancer. PeerJ 7, e7091 (2019).