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Published in: Cancer Cell International 1/2021

Open Access 01-12-2021 | NSCLC | Primary research

Ferroptosis-related gene AKR1C1 predicts the prognosis of non-small cell lung cancer

Authors: Fangfang Huang, Yushi Zheng, Xiaoling Li, Hui Luo, Lianxiang Luo

Published in: Cancer Cell International | Issue 1/2021

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Abstract

Background

Ferroptosis is a newly discovered mode of cell death distinct from apoptosis and necrosis, and its activation contributes to anticancer therapy in a variety of cancers. However, the prognostic value of ferroptosis-related genes in non-small cell lung cancer (NSCLC) remains to be further investigated.

Methods

NSCLC transcriptome mRNA-seq data set and corresponding clinical data set were downloaded from the Cancer Genome Atlas (TCGA). Then, bioinformatics approaches were subsequently employed to identify potential prognostic markers. Finally, the effects of candidate markers on NSCLC cell proliferation, migration, and ferroptosis were assessed by CCK8, colony formation, wound-healing assay, and functional assays related to ferroptosis.

Results

A total of 37 common differentially expressed genes were screened based TCGA database. Six overall survival associated genes (ENPP2, ULK1, CP, LURAP1L, HIC1, AKR1C1) were selected to build survival model, of which hub gene AKR1C1 was with high expression and low ferroptosis level in NSCLC tumor. Further research showed that AKR1C1 was related with many pathways involved in the process of ferroptosis and associated with diverse cancer-infiltrating immune cells. Moreover, the results of in vitro experiments indicated that the expression of AKR1C1 was upregulated in NSCLC cell lines, and silencing AKR1C1 can inhibit the proliferation and migration of NSCLC cells and promote the occurrence of ferroptosis.

Conclusions

Our study revealed the potential role of ferroptosis-related gene AKR1C1 in NSCLC, which can be used for prognostic prediction in NSCLC.
Appendix
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Literature
1.
2.
go back to reference Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;9:623. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;9:623.
3.
go back to reference Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin J, Beasley MB, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–60.PubMedCrossRef Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin J, Beasley MB, et al. The 2015 World Health Organization classification of lung tumors: impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol. 2015;10(9):1243–60.PubMedCrossRef
4.
go back to reference Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to The 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10(9):1240–2.PubMedCrossRef Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Introduction to The 2015 World Health Organization classification of tumors of the lung, pleura, thymus, and heart. J Thorac Oncol. 2015;10(9):1240–2.PubMedCrossRef
5.
go back to reference Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu YL, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389(10066):299–311.CrossRefPubMed Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu YL, et al. Lung cancer: current therapies and new targeted treatments. Lancet. 2017;389(10066):299–311.CrossRefPubMed
6.
go back to reference Kulasingam V, Diamandis EP. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Nat Clin Pract Oncol. 2008;5(10):588–99.PubMedCrossRef Kulasingam V, Diamandis EP. Strategies for discovering novel cancer biomarkers through utilization of emerging technologies. Nat Clin Pract Oncol. 2008;5(10):588–99.PubMedCrossRef
7.
go back to reference Nannini M, Pantaleo MA, Maleddu A, Astolfi A, Formica S, Biasco G. Gene expression profiling in colorectal cancer using microarray technologies: results and perspectives. Cancer Treat Rev. 2009;35(3):201–9.PubMedCrossRef Nannini M, Pantaleo MA, Maleddu A, Astolfi A, Formica S, Biasco G. Gene expression profiling in colorectal cancer using microarray technologies: results and perspectives. Cancer Treat Rev. 2009;35(3):201–9.PubMedCrossRef
8.
go back to reference Liao D, Yang G, Yang Y, Tang X, Huang H, Shao J, et al. Identification of Pannexin 2 as a Novel Marker Correlating with Ferroptosis and Malignant Phenotypes of Prostate Cancer Cells. Onco Targets Ther. 2020;13:4411–21.PubMedPubMedCentralCrossRef Liao D, Yang G, Yang Y, Tang X, Huang H, Shao J, et al. Identification of Pannexin 2 as a Novel Marker Correlating with Ferroptosis and Malignant Phenotypes of Prostate Cancer Cells. Onco Targets Ther. 2020;13:4411–21.PubMedPubMedCentralCrossRef
9.
go back to reference Shan Y, Yang G, Huang H, Zhou Y, Hu X, Lu Q, et al. Ubiquitin-like modifier activating enzyme 1 as a novel diagnostic and prognostic indicator that correlates with ferroptosis and the malignant phenotypes of liver cancer cells. Front Oncol. 2020;10:592413.PubMedPubMedCentralCrossRef Shan Y, Yang G, Huang H, Zhou Y, Hu X, Lu Q, et al. Ubiquitin-like modifier activating enzyme 1 as a novel diagnostic and prognostic indicator that correlates with ferroptosis and the malignant phenotypes of liver cancer cells. Front Oncol. 2020;10:592413.PubMedPubMedCentralCrossRef
10.
go back to reference Tang Y, Cui Y, Li Z, Jiao Z, Zhang Y, He Y, et al. Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res. 2016;35:7.PubMedPubMedCentralCrossRef Tang Y, Cui Y, Li Z, Jiao Z, Zhang Y, He Y, et al. Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells. J Exp Clin Cancer Res. 2016;35:7.PubMedPubMedCentralCrossRef
11.
go back to reference Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72.PubMedPubMedCentralCrossRef Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72.PubMedPubMedCentralCrossRef
12.
go back to reference Seibt TM, Proneth B, Conrad M. Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med. 2019;133:144–52.PubMedCrossRef Seibt TM, Proneth B, Conrad M. Role of GPX4 in ferroptosis and its pharmacological implication. Free Radic Biol Med. 2019;133:144–52.PubMedCrossRef
13.
go back to reference Macías-Rodríguez RU, Inzaugarat ME, Ruiz-Margáin A, Nelson LJ, Trautwein C, Cubero FJ. Reclassifying hepatic cell death during liver damage: ferroptosis-a novel form of non-apoptotic cell death? Int J Mol Sci. 2020;21:5.CrossRef Macías-Rodríguez RU, Inzaugarat ME, Ruiz-Margáin A, Nelson LJ, Trautwein C, Cubero FJ. Reclassifying hepatic cell death during liver damage: ferroptosis-a novel form of non-apoptotic cell death? Int J Mol Sci. 2020;21:5.CrossRef
14.
go back to reference Imai H, Matsuoka M, Kumagai T, Sakamoto T, Koumura T. Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis. Curr Top Microbiol Immunol. 2017;403:143–70.PubMed Imai H, Matsuoka M, Kumagai T, Sakamoto T, Koumura T. Lipid Peroxidation-Dependent Cell Death Regulated by GPx4 and Ferroptosis. Curr Top Microbiol Immunol. 2017;403:143–70.PubMed
15.
go back to reference Ma S, Henson ES, Chen Y, Gibson SB. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 2016;7(7):e2307.PubMedPubMedCentralCrossRef Ma S, Henson ES, Chen Y, Gibson SB. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 2016;7(7):e2307.PubMedPubMedCentralCrossRef
16.
go back to reference Gai C, Yu M, Li Z, Wang Y, Ding D, Zheng J, et al. Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer. J Cell Physiol. 2020;235(4):3329–39.PubMedCrossRef Gai C, Yu M, Li Z, Wang Y, Ding D, Zheng J, et al. Acetaminophen sensitizing erastin-induced ferroptosis via modulation of Nrf2/heme oxygenase-1 signaling pathway in non-small-cell lung cancer. J Cell Physiol. 2020;235(4):3329–39.PubMedCrossRef
17.
go back to reference Lou JS, Zhao LP, Huang ZH, Chen XY, Xu JT, Tai WC, et al. Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer. Phytomedicine. 2021;80:153370.PubMedCrossRef Lou JS, Zhao LP, Huang ZH, Chen XY, Xu JT, Tai WC, et al. Ginkgetin derived from Ginkgo biloba leaves enhances the therapeutic effect of cisplatin via ferroptosis-mediated disruption of the Nrf2/HO-1 axis in EGFR wild-type non-small-cell lung cancer. Phytomedicine. 2021;80:153370.PubMedCrossRef
18.
go back to reference Yamaguchi H, Hsu JL, Chen CT, Wang YN, Hsu MC, Chang SS, et al. Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin Cancer Res. 2013;19(4):845–54.PubMedPubMedCentralCrossRef Yamaguchi H, Hsu JL, Chen CT, Wang YN, Hsu MC, Chang SS, et al. Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin Cancer Res. 2013;19(4):845–54.PubMedPubMedCentralCrossRef
19.
go back to reference Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016;54:1–30.PubMedCrossRef Stelzer G, Rosen N, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, et al. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analyses. Curr Protoc Bioinformatics. 2016;54:1–30.PubMedCrossRef
20.
go back to reference Zhou N, Bao J. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database (Oxford). 2020;21020:87. Zhou N, Bao J. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database (Oxford). 2020;21020:87.
21.
go back to reference Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–40.PubMedCrossRef Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 2010;26(1):139–40.PubMedCrossRef
23.
go back to reference Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2010;38(Database issue):D355–60.PubMedCrossRef Kanehisa M, Goto S, Furumichi M, Tanabe M, Hirakawa M. KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 2010;38(Database issue):D355–60.PubMedCrossRef
24.
go back to reference Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.PubMedPubMedCentralCrossRef Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005;102(43):15545–50.PubMedPubMedCentralCrossRef
25.
go back to reference Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–8.PubMedCrossRef
26.
go back to reference Zhang H, Zhong J, Tu Y, Liu B, Chen Z, Luo Y, et al. Integrated bioinformatics analysis identifies hub genes associated with the pathogenesis and prognosis of esophageal squamous cell carcinoma. Biomed Res Int. 2019;2019:2615921.PubMedPubMedCentralCrossRef Zhang H, Zhong J, Tu Y, Liu B, Chen Z, Luo Y, et al. Integrated bioinformatics analysis identifies hub genes associated with the pathogenesis and prognosis of esophageal squamous cell carcinoma. Biomed Res Int. 2019;2019:2615921.PubMedPubMedCentralCrossRef
27.
go back to reference HyungJun C, Yu A, Sukwoo K, Jaewoo K, Hong S. Robust likelihood-based survival modeling with microarray data. J Stat Softw. 2008;29:20. HyungJun C, Yu A, Sukwoo K, Jaewoo K, Hong S. Robust likelihood-based survival modeling with microarray data. J Stat Softw. 2008;29:20.
28.
go back to reference Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, et al. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 2007;9(2):166–80.PubMedPubMedCentralCrossRef Rhodes DR, Kalyana-Sundaram S, Mahavisno V, Varambally R, Yu J, Briggs BB, et al. Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 2007;9(2):166–80.PubMedPubMedCentralCrossRef
29.
go back to reference Liu Z, Zhao Q, Zuo ZX, Yuan SQ, Yu K, Zhang Q, et al. Systematic Analysis of the Aberrances and Functional Implications of Ferroptosis in Cancer. iScience. 2020;23(7):101302.PubMedPubMedCentralCrossRef Liu Z, Zhao Q, Zuo ZX, Yuan SQ, Yu K, Zhang Q, et al. Systematic Analysis of the Aberrances and Functional Implications of Ferroptosis in Cancer. iScience. 2020;23(7):101302.PubMedPubMedCentralCrossRef
30.
go back to reference Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.PubMedCrossRef Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, et al. miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients. Breast Cancer Res Treat. 2016;160(3):439–46.PubMedCrossRef
31.
go back to reference Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160(1-2):48–61.PubMedPubMedCentralCrossRef Rooney MS, Shukla SA, Wu CJ, Getz G, Hacohen N. Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell. 2015;160(1-2):48–61.PubMedPubMedCentralCrossRef
32.
go back to reference Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017;77(21):e108–10.PubMedPubMedCentralCrossRef Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, et al. TIMER: A Web Server for Comprehensive Analysis of Tumor-Infiltrating Immune Cells. Cancer Res. 2017;77(21):e108–10.PubMedPubMedCentralCrossRef
33.
go back to reference Tian H, Li X, Jiang W, Lv C, Sun W, Huang C, et al. High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells. Lung Cancer. 2016;7:53–61.PubMedPubMedCentral Tian H, Li X, Jiang W, Lv C, Sun W, Huang C, et al. High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells. Lung Cancer. 2016;7:53–61.PubMedPubMedCentral
34.
go back to reference Rižner TL, Penning TM. Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism. Steroids. 2014;79:49–63.PubMedCrossRef Rižner TL, Penning TM. Role of aldo-keto reductase family 1 (AKR1) enzymes in human steroid metabolism. Steroids. 2014;79:49–63.PubMedCrossRef
35.
go back to reference Gagliardi M, Cotella D, Santoro C, Corà D, Barlev NA, Piacentini M, et al. Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis. Cell Death Dis. 2019;10(12):902.PubMedPubMedCentralCrossRef Gagliardi M, Cotella D, Santoro C, Corà D, Barlev NA, Piacentini M, et al. Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis. Cell Death Dis. 2019;10(12):902.PubMedPubMedCentralCrossRef
36.
go back to reference Rizner TL, Smuc T, Rupreht R, Sinkovec J, Penning TM. AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. Mol Cell Endocrinol. 2006;248(1-2):126–35.PubMedCrossRef Rizner TL, Smuc T, Rupreht R, Sinkovec J, Penning TM. AKR1C1 and AKR1C3 may determine progesterone and estrogen ratios in endometrial cancer. Mol Cell Endocrinol. 2006;248(1-2):126–35.PubMedCrossRef
37.
go back to reference Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66(5):2815–25.PubMedCrossRef Stanbrough M, Bubley GJ, Ross K, Golub TR, Rubin MA, Penning TM, et al. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006;66(5):2815–25.PubMedCrossRef
38.
go back to reference Zhou C, Shen G, Yang F, Duan J, Wu Z, Yang M, et al. Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells. J Cell Mol Med. 2020;24(11):6438–47.PubMedPubMedCentralCrossRef Zhou C, Shen G, Yang F, Duan J, Wu Z, Yang M, et al. Loss of AKR1C1 is a good prognostic factor in advanced NPC cases and increases chemosensitivity to cisplatin in NPC cells. J Cell Mol Med. 2020;24(11):6438–47.PubMedPubMedCentralCrossRef
39.
40.
go back to reference Angelova M, Charoentong P, Hackl H, Fischer ML, Snajder R, Krogsdam AM, et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol. 2015;16(1):64.PubMedPubMedCentralCrossRef Angelova M, Charoentong P, Hackl H, Fischer ML, Snajder R, Krogsdam AM, et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy. Genome Biol. 2015;16(1):64.PubMedPubMedCentralCrossRef
41.
go back to reference Lee N, Zakka LR, Mihm MJ, Schatton T. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology. 2016;48(2):177–87.PubMedCrossRef Lee N, Zakka LR, Mihm MJ, Schatton T. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology. 2016;48(2):177–87.PubMedCrossRef
42.
go back to reference Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.PubMedCrossRef Denkert C, von Minckwitz G, Darb-Esfahani S, Lederer B, Heppner BI, Weber KE, et al. Tumour-infiltrating lymphocytes and prognosis in different subtypes of breast cancer: a pooled analysis of 3771 patients treated with neoadjuvant therapy. Lancet Oncol. 2018;19(1):40–50.PubMedCrossRef
43.
go back to reference Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218.PubMedCrossRef Galon J, Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat Rev Drug Discov. 2019;18(3):197–218.PubMedCrossRef
44.
go back to reference Zhao Y, Schaafsma E, Gorlov IP, Hernando E, Thomas NE, Shen R, et al. A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis. Mol Cancer Res. 2019;17(1):109–19.PubMedCrossRef Zhao Y, Schaafsma E, Gorlov IP, Hernando E, Thomas NE, Shen R, et al. A Leukocyte Infiltration Score Defined by a Gene Signature Predicts Melanoma Patient Prognosis. Mol Cancer Res. 2019;17(1):109–19.PubMedCrossRef
45.
go back to reference Bremnes RM, Busund LT, Kilvær TL, Andersen S, Richardsen E, Paulsen EE, et al. The Role of Tumor-Infiltrating Lymphocytes in Development, Progression, and Prognosis of Non-Small Cell Lung Cancer. J Thorac Oncol. 2016;11(6):789–800.PubMedCrossRef Bremnes RM, Busund LT, Kilvær TL, Andersen S, Richardsen E, Paulsen EE, et al. The Role of Tumor-Infiltrating Lymphocytes in Development, Progression, and Prognosis of Non-Small Cell Lung Cancer. J Thorac Oncol. 2016;11(6):789–800.PubMedCrossRef
46.
go back to reference Zanetti M. Tapping CD4 T cells for cancer immunotherapy: the choice of personalized genomics. J Immunol. 2015;194(5):2049–56.PubMedCrossRef Zanetti M. Tapping CD4 T cells for cancer immunotherapy: the choice of personalized genomics. J Immunol. 2015;194(5):2049–56.PubMedCrossRef
47.
go back to reference Végran F, Apetoh L, Ghiringhelli F. Th9 cells: a novel CD4 T-cell subset in the immune war against cancer. Cancer Res. 2015;75(3):475–9.PubMedCrossRef Végran F, Apetoh L, Ghiringhelli F. Th9 cells: a novel CD4 T-cell subset in the immune war against cancer. Cancer Res. 2015;75(3):475–9.PubMedCrossRef
48.
go back to reference Kwak JW, Laskowski J, Li HY, McSharry MV, Sippel TR, Bullock BL, et al. Complement Activation via a C3a Receptor Pathway Alters CD4(+) T Lymphocytes and Mediates Lung Cancer Progression. Cancer Res. 2018;78(1):143–56.PubMedCrossRef Kwak JW, Laskowski J, Li HY, McSharry MV, Sippel TR, Bullock BL, et al. Complement Activation via a C3a Receptor Pathway Alters CD4(+) T Lymphocytes and Mediates Lung Cancer Progression. Cancer Res. 2018;78(1):143–56.PubMedCrossRef
49.
go back to reference Zeng G. MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design. J Immunother. 2001;24(3):195–204.PubMedCrossRef Zeng G. MHC class II-restricted tumor antigens recognized by CD4+ T cells: new strategies for cancer vaccine design. J Immunother. 2001;24(3):195–204.PubMedCrossRef
50.
go back to reference Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–96.PubMedCrossRef Steinman RM. The dendritic cell system and its role in immunogenicity. Annu Rev Immunol. 1991;9:271–96.PubMedCrossRef
51.
go back to reference Arai R, Soda S, Okutomi T, Morita H, Ohmi F, Funakoshi T, et al. Lipid accumulation in peripheral blood dendritic cells and anticancer immunity in patients with lung cancer. J Immunol Res. 2018;2018:5708239.PubMedPubMedCentralCrossRef Arai R, Soda S, Okutomi T, Morita H, Ohmi F, Funakoshi T, et al. Lipid accumulation in peripheral blood dendritic cells and anticancer immunity in patients with lung cancer. J Immunol Res. 2018;2018:5708239.PubMedPubMedCentralCrossRef
52.
go back to reference Zeid NA, Muller HK. S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology. 1993;25(4):338–43.PubMedCrossRef Zeid NA, Muller HK. S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology. 1993;25(4):338–43.PubMedCrossRef
53.
go back to reference Ishikawa A, Motohashi S, Ishikawa E, Fuchida H, Higashino K, Otsuji M, et al. A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res. 2005;11(5):1910–7.PubMedCrossRef Ishikawa A, Motohashi S, Ishikawa E, Fuchida H, Higashino K, Otsuji M, et al. A phase I study of alpha-galactosylceramide (KRN7000)-pulsed dendritic cells in patients with advanced and recurrent non-small cell lung cancer. Clin Cancer Res. 2005;11(5):1910–7.PubMedCrossRef
54.
go back to reference Chang GC, Lan HC, Juang SH, Wu YC, Lee HC, Hung YM, et al. A pilot clinical trial of vaccination with dendritic cells pulsed with autologous tumor cells derived from malignant pleural effusion in patients with late-stage lung carcinoma. Cancer. 2005;103(4):763–71.PubMedCrossRef Chang GC, Lan HC, Juang SH, Wu YC, Lee HC, Hung YM, et al. A pilot clinical trial of vaccination with dendritic cells pulsed with autologous tumor cells derived from malignant pleural effusion in patients with late-stage lung carcinoma. Cancer. 2005;103(4):763–71.PubMedCrossRef
Metadata
Title
Ferroptosis-related gene AKR1C1 predicts the prognosis of non-small cell lung cancer
Authors
Fangfang Huang
Yushi Zheng
Xiaoling Li
Hui Luo
Lianxiang Luo
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2021
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-021-02267-2

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