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Published in: Cancer Cell International 1/2020

Open Access 01-12-2020 | Primary research

An individualized immune prognostic signature in lung adenocarcinoma

Authors: Liangdong Sun, Gening Jiang, Diego Gonzalez-Rivas, Peng Zhang

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Tumor immune infiltration is closely associated with clinical outcome in lung cancer. We aimed to develop an immune signature to improve the prognostic predictions of lung adenocarcinoma (LUAD).

Methods

We applied “Cell type Identification by Estimating Relative Subsets of RNA Transcripts” method to quantify the fraction of 22 leukocyte cells from six public microarray datasets. Four datasets from GPL570 were treated as the training cohort and two datasets from GPL96 and GPL10379 as the validation cohorts. An immune risk score (IRS) based on leukocyte cell fraction was established by least absolute shrinkage and selection operator cox regression model.

Results

IRS consisting of 6 types of leukocytes was constructed in the training dataset. In the training cohort (520 patients), the IRS stratified patients into high-IRS group (215 patients) and low-IRS group (305 patients) with significant differences in overall survival (OS) (HR: 2.77, 95% CI 2.08–3.06). Multivariate analysis including age, gender, stage, IRS and tumor purity revealed the IRS to be an independent prognostic factor in all datasets (training: HR: 10.71, 95% CI 5.72–20.07; validation-1: HR 2.68, 95% CI 1.15–6.27; validation-2: HR 3.71, 95% CI 1.33–10.33); all p < 0.05). IRS was significantly positively correlated to the expression levels of PD1, PDL1, CTLA and LAG3 (all p < 0.001). When integrated with clinical characteristics including stage and age, the composite immune and clinical signature presented with improved prognostic accuracy than IRS (mean C-index 0.66 vs. 0.60).

Conclusions

The proposed immune-clinical signature could predict OS in patients with LUAD effectively.
Appendix
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Literature
3.
go back to reference Network CGAR. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543.CrossRef Network CGAR. Comprehensive molecular profiling of lung adenocarcinoma. Nature. 2014;511:543.CrossRef
4.
go back to reference Lin JJ, Cardarella S, Lydon CA, Dahlberg SE, Jackman DM, Jänne PA, et al. Five-year survival in egfr-mutant metastatic lung adenocarcinoma treated with egfr-tkis. J Thorac Oncol. 2016;11:556–65.PubMedCrossRef Lin JJ, Cardarella S, Lydon CA, Dahlberg SE, Jackman DM, Jänne PA, et al. Five-year survival in egfr-mutant metastatic lung adenocarcinoma treated with egfr-tkis. J Thorac Oncol. 2016;11:556–65.PubMedCrossRef
5.
6.
go back to reference Remark R, Becker C, Gomez JE, Damotte D, Dieu-Nosjean M-C, Sautès-Fridman C, et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am J Respir Crit Care Med. 2015;191:377–90.PubMedPubMedCentralCrossRef Remark R, Becker C, Gomez JE, Damotte D, Dieu-Nosjean M-C, Sautès-Fridman C, et al. The non-small cell lung cancer immune contexture. A major determinant of tumor characteristics and patient outcome. Am J Respir Crit Care Med. 2015;191:377–90.PubMedPubMedCentralCrossRef
7.
go back to reference Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A, Graziano S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non–small-cell lung cancer. J Clin Oncol. 2016;34:1223.PubMedPubMedCentralCrossRef Brambilla E, Le Teuff G, Marguet S, Lantuejoul S, Dunant A, Graziano S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non–small-cell lung cancer. J Clin Oncol. 2016;34:1223.PubMedPubMedCentralCrossRef
8.
go back to reference Kilic A, Landreneau RJ, Luketich JD, Pennathur A, Schuchert MJ. Density of tumor-infiltrating lymphocytes correlates with disease recurrence and survival in patients with large non-small-cell lung cancer tumors. J Surg Res. 2011;167:207–10.PubMedCrossRef Kilic A, Landreneau RJ, Luketich JD, Pennathur A, Schuchert MJ. Density of tumor-infiltrating lymphocytes correlates with disease recurrence and survival in patients with large non-small-cell lung cancer tumors. J Surg Res. 2011;167:207–10.PubMedCrossRef
9.
go back to reference Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298.PubMedCrossRef Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12:298.PubMedCrossRef
10.
go back to reference Muppa P, Terra SPB, Sharma A, Mansfield AS, Aubry M-C, Bhinge K, et al. Immune cell infiltration may be a key determinant of long-term survival in small cell lung cancer. J Thorac Oncol. 2019;14(7):1286–95.PubMedCrossRef Muppa P, Terra SPB, Sharma A, Mansfield AS, Aubry M-C, Bhinge K, et al. Immune cell infiltration may be a key determinant of long-term survival in small cell lung cancer. J Thorac Oncol. 2019;14(7):1286–95.PubMedCrossRef
12.
go back to reference Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453.PubMedPubMedCentralCrossRef Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, et al. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453.PubMedPubMedCentralCrossRef
13.
go back to reference Xiong Y, Wang K, Zhou H, Peng L, You W, Fu Z. Profiles of immune infiltration in colorectal cancer and their clinical significant: a gene expression-based study. Cancer Med. 2018;7:4496–508.PubMedPubMedCentralCrossRef Xiong Y, Wang K, Zhou H, Peng L, You W, Fu Z. Profiles of immune infiltration in colorectal cancer and their clinical significant: a gene expression-based study. Cancer Med. 2018;7:4496–508.PubMedPubMedCentralCrossRef
14.
go back to reference Ali HR, Chlon L, Pharoah PD, Markowetz F, Caldas C. Patterns of immune infiltration in breast cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13:e1002194.PubMedPubMedCentralCrossRef Ali HR, Chlon L, Pharoah PD, Markowetz F, Caldas C. Patterns of immune infiltration in breast cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 2016;13:e1002194.PubMedPubMedCentralCrossRef
15.
go back to reference Rohr-Udilova N, Klinglmüller F, Schulte-Hermann R, Stift J, Herac M, Salzmann M, et al. Deviations of the immune cell landscape between healthy liver and hepatocellular carcinoma. Sci Rep. 2018;8:6220.PubMedPubMedCentralCrossRef Rohr-Udilova N, Klinglmüller F, Schulte-Hermann R, Stift J, Herac M, Salzmann M, et al. Deviations of the immune cell landscape between healthy liver and hepatocellular carcinoma. Sci Rep. 2018;8:6220.PubMedPubMedCentralCrossRef
16.
go back to reference Mony JT, Schuchert MJ. Prognostic implications of heterogeneity in intra-tumoral immune composition for recurrence in early stage lung cancer. Front Immunol. 2018;9:2298.PubMedPubMedCentralCrossRef Mony JT, Schuchert MJ. Prognostic implications of heterogeneity in intra-tumoral immune composition for recurrence in early stage lung cancer. Front Immunol. 2018;9:2298.PubMedPubMedCentralCrossRef
17.
go back to reference Kurbatov V, Balayev A, Saffarzadeh A, Heller DR, Boffa DJ, Blasberg JD, et al. Digital inference of immune microenvironment reveals low-risk subtype of early lung adenocarcinoma. Ann Thorac Surg. 2020;109:343–9.PubMedCrossRef Kurbatov V, Balayev A, Saffarzadeh A, Heller DR, Boffa DJ, Blasberg JD, et al. Digital inference of immune microenvironment reveals low-risk subtype of early lung adenocarcinoma. Ann Thorac Surg. 2020;109:343–9.PubMedCrossRef
18.
go back to reference Yamauchi M, Yamaguchi R, Nakata A, Kohno T, Nagasaki M, Shimamura T et al. Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma. PloS ONE. 2012;7. Yamauchi M, Yamaguchi R, Nakata A, Kohno T, Nagasaki M, Shimamura T et al. Epidermal growth factor receptor tyrosine kinase defines critical prognostic genes of stage I lung adenocarcinoma. PloS ONE. 2012;7.
19.
go back to reference Rousseaux S, Debernardi A, Jacquiau B, Vitte AL, Vesin A, Nagymignotte H, et al. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med. 2013;5:86ra66.CrossRef Rousseaux S, Debernardi A, Jacquiau B, Vitte AL, Vesin A, Nagymignotte H, et al. Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers. Sci Transl Med. 2013;5:86ra66.CrossRef
20.
go back to reference Jabs V, Edlund K, König H, Grinberg M, Micke P. Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer. PLoS ONE. 2017;12:e0187246.PubMedPubMedCentralCrossRef Jabs V, Edlund K, König H, Grinberg M, Micke P. Integrative analysis of genome-wide gene copy number changes and gene expression in non-small cell lung cancer. PLoS ONE. 2017;12:e0187246.PubMedPubMedCentralCrossRef
21.
go back to reference Der SD, Sykes J, Pintilie M, et al. Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage ia patients. J Throac Ocol. 2014;9:59–64.CrossRef Der SD, Sykes J, Pintilie M, et al. Validation of a histology-independent prognostic gene signature for early-stage, non-small-cell lung cancer including stage ia patients. J Throac Ocol. 2014;9:59–64.CrossRef
22.
go back to reference Shedden K, Taylor JMG, Enkemann SA, Tsao M-S, Yeatman TJ, Gerald WL, et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med. 2008;14:822–7.PubMedPubMedCentralCrossRef Shedden K, Taylor JMG, Enkemann SA, Tsao M-S, Yeatman TJ, Gerald WL, et al. Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study. Nat Med. 2008;14:822–7.PubMedPubMedCentralCrossRef
23.
go back to reference Schabath MB, Welsh EA, Fulp WJ, Chen L, Teer JK, Thompson ZJ, et al. Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene. 2016;35(24):3209–16.PubMedCrossRef Schabath MB, Welsh EA, Fulp WJ, Chen L, Teer JK, Thompson ZJ, et al. Differential association of STK11 and TP53 with KRAS mutation-associated gene expression, proliferation and immune surveillance in lung adenocarcinoma. Oncogene. 2016;35(24):3209–16.PubMedCrossRef
24.
go back to reference Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28:882–3.PubMedPubMedCentralCrossRef Leek JT, Johnson WE, Parker HS, Jaffe AE, Storey JD. The sva package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012;28:882–3.PubMedPubMedCentralCrossRef
25.
go back to reference Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The iaslc lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.PubMedCrossRef Goldstraw P, Crowley J, Chansky K, Giroux DJ, Groome PA, Rami-Porta R, et al. The iaslc lung cancer staging project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2:706–14.PubMedCrossRef
26.
go back to reference Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.PubMedCrossRef Yoshihara K, Shahmoradgoli M, Martínez E, Vegesna R, Kim H, Torres-Garcia W, et al. Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun. 2013;4:2612.PubMedCrossRef
27.
go back to reference Kassambara A, Kosinski M, Biecek P. Survminer: drawing survival curves using’ggplot2’. R package version 03 2017;1. Kassambara A, Kosinski M, Biecek P. Survminer: drawing survival curves using’ggplot2’. R package version 03 2017;1.
28.
go back to reference Goeman JJ. L1 penalized estimation in the cox proportional hazards model. Biometric J. 2010;52:70–84. Goeman JJ. L1 penalized estimation in the cox proportional hazards model. Biometric J. 2010;52:70–84.
29.
go back to reference Simon N, Friedman J, Hastie T, Tibshirani R. Regularization paths for cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011;39:1.PubMedPubMedCentralCrossRef Simon N, Friedman J, Hastie T, Tibshirani R. Regularization paths for cox’s proportional hazards model via coordinate descent. J Stat Softw. 2011;39:1.PubMedPubMedCentralCrossRef
30.
go back to reference Kamarudin AN, Cox T, Kolamunnage-Dona R. Time-dependent roc curve analysis in medical research: current methods and applications. BMC Med Res Methodol. 2017;17:53.PubMedPubMedCentralCrossRef Kamarudin AN, Cox T, Kolamunnage-Dona R. Time-dependent roc curve analysis in medical research: current methods and applications. BMC Med Res Methodol. 2017;17:53.PubMedPubMedCentralCrossRef
31.
go back to reference Uno H, Claggett B, Tian L, Inoue E, Gallo P, Miyata T, et al. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J Clin Oncol. 2014;32:2380.PubMedPubMedCentralCrossRef Uno H, Claggett B, Tian L, Inoue E, Gallo P, Miyata T, et al. Moving beyond the hazard ratio in quantifying the between-group difference in survival analysis. J Clin Oncol. 2014;32:2380.PubMedPubMedCentralCrossRef
32.
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. 2005;102:15545–50.PubMedCrossRefPubMedCentral 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. 2005;102:15545–50.PubMedCrossRefPubMedCentral
33.
go back to reference Uno H, Tian L, CroninA, Battioui C, Horiguchi M, Uno MH. Package ‘survrm2’. 2017. Uno H, Tian L, CroninA, Battioui C, Horiguchi M, Uno MH. Package ‘survrm2’. 2017.
34.
go back to reference Wakabayashi O, Yamazaki K, Oizumi S, Hommura F, Kinoshita I, Ogura S, et al. CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci. 2003;94:1003–9.PubMedCrossRef Wakabayashi O, Yamazaki K, Oizumi S, Hommura F, Kinoshita I, Ogura S, et al. CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non-small cell lung cancers. Cancer Sci. 2003;94:1003–9.PubMedCrossRef
35.
go back to reference Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund L-T. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008;14:5220–7.PubMedCrossRef Al-Shibli KI, Donnem T, Al-Saad S, Persson M, Bremnes RM, Busund L-T. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008;14:5220–7.PubMedCrossRef
36.
go back to reference Kurebayashi Y, Emoto K, Hayashi Y, Kamiyama I, Ohtsuka T, Asamura H, et al. Comprehensive immune profiling of lung adenocarcinomas reveals four immunosubtypes with plasma cell subtype a negative indicator. Cancer Immunol Res. 2016;4:234–47.PubMedCrossRef Kurebayashi Y, Emoto K, Hayashi Y, Kamiyama I, Ohtsuka T, Asamura H, et al. Comprehensive immune profiling of lung adenocarcinomas reveals four immunosubtypes with plasma cell subtype a negative indicator. Cancer Immunol Res. 2016;4:234–47.PubMedCrossRef
37.
go back to reference Kataki A, Scheid P, Piet M, Marie B, Martinet N, Martinet Y, et al. Tumor infiltrating lymphocytes and macrophages have a potential dual role in lung cancer by supporting both host-defense and tumor progression. J Lab Clin Med. 2002;140:320–8.PubMedCrossRef Kataki A, Scheid P, Piet M, Marie B, Martinet N, Martinet Y, et al. Tumor infiltrating lymphocytes and macrophages have a potential dual role in lung cancer by supporting both host-defense and tumor progression. J Lab Clin Med. 2002;140:320–8.PubMedCrossRef
38.
go back to reference Tomita M, Matsuzaki Y, Onitsuka T. Correlation between mast cells and survival rates in patients with pulmonary adenocarcinoma. Lung Cancer. 1999;26:103–8.PubMedCrossRef Tomita M, Matsuzaki Y, Onitsuka T. Correlation between mast cells and survival rates in patients with pulmonary adenocarcinoma. Lung Cancer. 1999;26:103–8.PubMedCrossRef
39.
go back to reference Yang Z, Zhang B, Li D, Lv M, Huang C, Shen GX et al. Mast cells mobilize myeloid-derived suppressor cells and treg cells in tumor microenvironment via il-17 pathway in murine hepatocarcinoma model. Plos ONE. 2010;5. Yang Z, Zhang B, Li D, Lv M, Huang C, Shen GX et al. Mast cells mobilize myeloid-derived suppressor cells and treg cells in tumor microenvironment via il-17 pathway in murine hepatocarcinoma model. Plos ONE. 2010;5.
40.
go back to reference Takanami I, Takeuchi K, Naruke M. Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma. Cancer. 2000;88:2686–92.CrossRefPubMed Takanami I, Takeuchi K, Naruke M. Mast cell density is associated with angiogenesis and poor prognosis in pulmonary adenocarcinoma. Cancer. 2000;88:2686–92.CrossRefPubMed
41.
go back to reference Ilie M, Hofman V, Ortholan C, Bonnetaud C, Coëlle C, Mouroux J, et al. Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive t-cell ratio in patients with resectable non-small cell lung cancer. Cancer. 2012;118:1726–37.PubMedCrossRef Ilie M, Hofman V, Ortholan C, Bonnetaud C, Coëlle C, Mouroux J, et al. Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive t-cell ratio in patients with resectable non-small cell lung cancer. Cancer. 2012;118:1726–37.PubMedCrossRef
42.
go back to reference Rakaee M, Busund LT, Paulsen EE, Richardsen E, Kilvaer TK. Prognostic effect of intratumoral neutrophils across histological subtypes of non-small cell lung cancer. Oncotarget. 2016;7:72184–96.PubMedPubMedCentralCrossRef Rakaee M, Busund LT, Paulsen EE, Richardsen E, Kilvaer TK. Prognostic effect of intratumoral neutrophils across histological subtypes of non-small cell lung cancer. Oncotarget. 2016;7:72184–96.PubMedPubMedCentralCrossRef
43.
go back to reference Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.PubMedCrossRef Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C, et al. Towards the introduction of the ‘immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.PubMedCrossRef
44.
go back to reference Angell H, Galon J. From the immune contexture to the immunoscore: the role of prognostic and predictive immune markers in cancer. Curr Opin Immunol. 2013;25:261–7.PubMedCrossRef Angell H, Galon J. From the immune contexture to the immunoscore: the role of prognostic and predictive immune markers in cancer. Curr Opin Immunol. 2013;25:261–7.PubMedCrossRef
45.
go back to reference Galon J, Pagès F, Marincola FM, Thurin M, Trinchieri G, Fox BA et al. The immune score as a new possible approach for the classification of cancer. BioMed Central. 2012. Galon J, Pagès F, Marincola FM, Thurin M, Trinchieri G, Fox BA et al. The immune score as a new possible approach for the classification of cancer. BioMed Central. 2012.
46.
go back to reference Busch SE, Hanke ML, Kargl J, Metz HE, MacPherson D, Houghton AM. Lung cancer subtypes generate unique immune responses. J Immunol. 2016;197:4493–503.PubMedCrossRef Busch SE, Hanke ML, Kargl J, Metz HE, MacPherson D, Houghton AM. Lung cancer subtypes generate unique immune responses. J Immunol. 2016;197:4493–503.PubMedCrossRef
47.
go back to reference Zhou R, Zhang J, Zeng D, Sun H, Rong X, Shi M, et al. Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage i–iii colon cancer. Cancer Immunol Immunother. 2019;68:433–42.PubMedCrossRef Zhou R, Zhang J, Zeng D, Sun H, Rong X, Shi M, et al. Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage i–iii colon cancer. Cancer Immunol Immunother. 2019;68:433–42.PubMedCrossRef
48.
go back to reference Zeng D, Zhou R, Yu Y, Luo Y, Zhang J, Sun H, et al. Gene expression profiles for a prognostic immunoscore in gastric cancer. Br J Surg. 2018;105:1338–48.PubMedPubMedCentralCrossRef Zeng D, Zhou R, Yu Y, Luo Y, Zhang J, Sun H, et al. Gene expression profiles for a prognostic immunoscore in gastric cancer. Br J Surg. 2018;105:1338–48.PubMedPubMedCentralCrossRef
49.
50.
go back to reference Tibshirani R. The lasso method for variable selection in the cox model. Stat Med. 1997;16:385–95.PubMedCrossRef Tibshirani R. The lasso method for variable selection in the cox model. Stat Med. 1997;16:385–95.PubMedCrossRef
51.
go back to reference Lin T, Fu Y, Zhang X, Gu J, Ma X, Miao R, et al. A seven-long noncoding rna signature predicts overall survival for patients with early stage non-small cell lung cancer. Aging. 2018;10:2356.PubMedPubMedCentralCrossRef Lin T, Fu Y, Zhang X, Gu J, Ma X, Miao R, et al. A seven-long noncoding rna signature predicts overall survival for patients with early stage non-small cell lung cancer. Aging. 2018;10:2356.PubMedPubMedCentralCrossRef
52.
go back to reference Li B, Cui Y, Diehn M, Li R. Development and validation of an individualized immune prognostic signature in early-stage non-squamous non-small cell lung cancer. JAMA Oncol. 2017;3:1529–37.PubMedPubMedCentralCrossRef Li B, Cui Y, Diehn M, Li R. Development and validation of an individualized immune prognostic signature in early-stage non-squamous non-small cell lung cancer. JAMA Oncol. 2017;3:1529–37.PubMedPubMedCentralCrossRef
53.
go back to reference Song Q, Shang J, Yang Z, Zhang L, Zhang C, Chen J, et al. Identification of an immune signature predicting prognosis risk of patients in lung adenocarcinoma. J Transl Med. 2019;17(1):70.PubMedPubMedCentralCrossRef Song Q, Shang J, Yang Z, Zhang L, Zhang C, Chen J, et al. Identification of an immune signature predicting prognosis risk of patients in lung adenocarcinoma. J Transl Med. 2019;17(1):70.PubMedPubMedCentralCrossRef
54.
go back to reference Holmes CE, Ruckdeschel JC, Johnston M, Thomas PA, Long S. Randomized trial of lobectomy versus limited resection for t1 n0 non-small-cell lung-cancer. Ann Thorac Surg. 1995;60:615–22.CrossRef Holmes CE, Ruckdeschel JC, Johnston M, Thomas PA, Long S. Randomized trial of lobectomy versus limited resection for t1 n0 non-small-cell lung-cancer. Ann Thorac Surg. 1995;60:615–22.CrossRef
55.
go back to reference Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16(5):275–87.PubMedPubMedCentralCrossRef Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer. 2016;16(5):275–87.PubMedPubMedCentralCrossRef
Metadata
Title
An individualized immune prognostic signature in lung adenocarcinoma
Authors
Liangdong Sun
Gening Jiang
Diego Gonzalez-Rivas
Peng Zhang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2020
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-020-01237-4

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