Eight-gene prognostic signature associated with hypoxia and ferroptosis for gastric cancer with general applicability
Abstract
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. . 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. . 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. Gastric cancer prevention strategies: a global perspective. J. Gastroenterol. Hepatol. 35, 1495–1502 (2020).
- 4. Comprehensive pharmacogenomic characterization of gastric cancer. Genome Med. 12(1), 1–12 (2020).
- 5. . Gastric cancer: a comprehensive review of current and future treatment strategies. 39(4), 1179–1203 (2020).
- 6. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5), 1060–1072 (2012).
- 7. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171(2), 273–285 (2017).
- 8. Ferroptosis: process and function. Cell Death Differ. 23(3), 369–379 (2016).
- 9. . 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. . Hypoxia inducible factor (HIF) in the tumor microenvironment: friend or foe? Sci. China Life Sci. 60(10), 1114–1124 (2017).
- 11. 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. Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance. Cancer Biol. Ther. 17(4), 400–406 (2016).
- 13. . Molecular mechanisms of chemoresistance in gastric cancer. World J. Gastrointest. Oncol. 8(9), 673 (2016).
- 14. . Molecular signaling pathways involved in gastric cancer chemoresistance. In: Theranostics Approaches to Gastric and Colon Cancer. Springer, 117–134 (2020).
- 15. The proteogenomic landscape of curable prostate cancer. Cancer Cell 35(3), 414–427.e416 (2019).
- 16. MYC activation cooperates with Vhl and Ink4a/Arf loss to induce clear cell renal cell carcinoma. Nat. Commun. 8(1), 1–12 (2017).
- 17. . 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. . A robust nine-gene prognostic signature associated with tumour doubling time for hepatocellular carcinoma. Life Sci. 260, 118396–118396 (2020).
- 19. Pan-cancer immunogenomic analyses reveal genotype–immunophenotype relationships and predictors of response to checkpoint blockade. Cell Rep. 18(1), 248–262 (2017).
- 20. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12(5), 453–457 (2015).
- 21. . Comparison and applicability of molecular classifications for gastric cancer. Cancer Treat Rev. 77, 29–34 (2019).
- 22. 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. . Fate-mapping post-hypoxic tumor cells reveals a ROS-resistant phenotype that promotes metastasis. Nat. Commun. 10(1), 1–18 (2019).
- 24. 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. . Impact of stromal cell components of tumor microenvironment on epithelial-mesenchymal transition in breast cancer cells. Exp. Oncol. 36, 72–78 (2014).
- 26. . 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. 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. DUSP1 induces apatinib resistance by activating the MAPK pathway in gastric cancer. Oncol. Rep. 40(3), 1203–1222 (2018).
- 29. . 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. . MiR-144 functions as tumor suppressor by targeting PIM1 in gastric cancer. Eur. Rev. Med. Pharmacol. Sci. 21(13), 3028 (2017).
- 31. Stanniocalcin-1 promotes cell proliferation, chemoresistance and metastasis in hypoxic gastric cancer cells via Bcl-2. Oncol. Rep. 41(3), 1998–2008 (2019).
- 32. ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity. Elife 7, e33057 (2018).
- 33. . Global transcriptomic analysis identifies SERPINE1 as a prognostic biomarker associated with epithelial-to-mesenchymal transition in gastric cancer. PeerJ 7, e7091 (2019).