Skip to main content
Top
Published in: BMC Cancer 1/2020

01-12-2020 | Gastric Cancer | Research article

Identification of immune cells and mRNA associated with prognosis of gastric cancer

Authors: Mingming Wang, Zedong Li, Yu Peng, Jianyu Fang, Tao Fang, Jiajia Wu, Jun Zhou

Published in: BMC Cancer | Issue 1/2020

Login to get access

Abstract

Background

The clinical success demonstrates the enormous potential of immunotherapy in cancer treatment.

Methods

This article presented research linking gastric cancer to immune cells, based on RNA-seq data of Stomach adenocarcinoma (STAD) and gene expression profile of GSE84437, 24 kinds of tumor-infiltrating immune cells were quantified by single-sample gene set enrichment analysis.

Results

Th2 cells, T helper cells, and Mast cells were identified as prognostic immune cells in both TCGA and GEO groups. Then SUPV3L1 and SLC22A17 were identified as hub genes which may affect immune cell infiltration by correlation analysis. Survival analysis further proved that hub genes and prognostic immune cells are associated with the prognosis of gastric cancer. In gastrointestinal tumors, hub genes and prognostic immune cells also found differences in non-tumor and tumor tissues.

Conclusions

We found that three immune cells infiltration are associated with the prognosis of gastric cancer and further identify two hub genes. These two key genes may affect immune cell infiltration, result in the different prognosis of patients.
Literature
1.
go back to reference Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353(25):2654–66.CrossRef Pages F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R, Mlecnik B, Kirilovsky A, Nilsson M, Damotte D, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353(25):2654–66.CrossRef
2.
go back to reference Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.CrossRef Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C, Tosolini M, Camus M, Berger A, Wind P, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313(5795):1960–4.CrossRef
3.
go back to reference Fridman WH, Zitvogel L, Sautes-Fridman C, Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 2017;14(12):717–34.CrossRef Fridman WH, Zitvogel L, Sautes-Fridman C, Kroemer G. The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol. 2017;14(12):717–34.CrossRef
4.
go back to reference Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–14.CrossRef Sharma P, Allison JP. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential. Cell. 2015;161(2):205–14.CrossRef
5.
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(4):298–306.CrossRef Fridman WH, Pages F, Sautes-Fridman C, Galon J. The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer. 2012;12(4):298–306.CrossRef
6.
go back to reference Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321–30.CrossRef Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541(7637):321–30.CrossRef
7.
go back to reference Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.CrossRef Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.CrossRef
8.
go back to reference Finotello F, Trajanoski Z. Quantifying tumor-infiltrating immune cells from transcriptomics data. Cancer Immunol Immunother. 2018;67(7):1031–40.CrossRef Finotello F, Trajanoski Z. Quantifying tumor-infiltrating immune cells from transcriptomics data. Cancer Immunol Immunother. 2018;67(7):1031–40.CrossRef
9.
go back to reference Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462(7269):108–12.CrossRef Barbie DA, Tamayo P, Boehm JS, Kim SY, Moody SE, Dunn IF, Schinzel AC, Sandy P, Meylan E, Scholl C, et al. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009;462(7269):108–12.CrossRef
10.
go back to reference Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39(4):782–95.CrossRef Bindea G, Mlecnik B, Tosolini M, Kirilovsky A, Waldner M, Obenauf AC, Angell H, Fredriksen T, Lafontaine L, Berger A, et al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity. 2013;39(4):782–95.CrossRef
11.
go back to reference Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018;28(11):1747–56.CrossRef Mayakonda A, Lin DC, Assenov Y, Plass C, Koeffler HP. Maftools: efficient and comprehensive analysis of somatic variants in cancer. Genome Res. 2018;28(11):1747–56.CrossRef
12.
go back to reference Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, et al. TCGAbiolinks: an R/bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 2016;44(8):e71.CrossRef Colaprico A, Silva TC, Olsen C, Garofano L, Cava C, Garolini D, Sabedot TS, Malta TM, Pagnotta SM, Castiglioni I, et al. TCGAbiolinks: an R/bioconductor package for integrative analysis of TCGA data. Nucleic Acids Res. 2016;44(8):e71.CrossRef
13.
go back to reference Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, Boussioutas A, Busuttil R, Szabo A, Gyorffy B. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget. 2016;7(31):49322–33.CrossRef Szasz AM, Lanczky A, Nagy A, Forster S, Hark K, Green JE, Boussioutas A, Busuttil R, Szabo A, Gyorffy B. Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients. Oncotarget. 2016;7(31):49322–33.CrossRef
14.
go back to reference Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, 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.CrossRef Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, 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.CrossRef
15.
go back to reference Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284–7.CrossRef Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16(5):284–7.CrossRef
16.
go back to reference Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest. 2015;125(9):3335–7.CrossRef Yang Y. Cancer immunotherapy: harnessing the immune system to battle cancer. J Clin Invest. 2015;125(9):3335–7.CrossRef
17.
go back to reference Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.CrossRef Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.CrossRef
18.
go back to reference Brentjens RJ, Latouche JB, Santos E, Marti F, Gong MC, Lyddane C, King PD, Larson S, Weiss M, Riviere I, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med. 2003;9(3):279–86.CrossRef Brentjens RJ, Latouche JB, Santos E, Marti F, Gong MC, Lyddane C, King PD, Larson S, Weiss M, Riviere I, et al. Eradication of systemic B-cell tumors by genetically targeted human T lymphocytes co-stimulated by CD80 and interleukin-15. Nat Med. 2003;9(3):279–86.CrossRef
19.
go back to reference Lorvik KB, Hammarstrom C, Fauskanger M, Haabeth OA, Zangani M, Haraldsen G, Bogen B, Corthay A. Adoptive transfer of tumor-specific Th2 cells eradicates tumors by triggering an in situ inflammatory immune response. Cancer Res. 2016;76(23):6864–76.CrossRef Lorvik KB, Hammarstrom C, Fauskanger M, Haabeth OA, Zangani M, Haraldsen G, Bogen B, Corthay A. Adoptive transfer of tumor-specific Th2 cells eradicates tumors by triggering an in situ inflammatory immune response. Cancer Res. 2016;76(23):6864–76.CrossRef
20.
go back to reference Bohner P, Chevalier MF, Cesson V, Rodrigues-Dias SC, Dartiguenave F, Burruni R, Tawadros T, Valerio M, Lucca I, Nardelli-Haefliger D, et al. Double positive CD4(+)CD8(+) T cells are enriched in urological cancers and favor T Helper-2 polarization. Front Immunol. 2019;10:622.CrossRef Bohner P, Chevalier MF, Cesson V, Rodrigues-Dias SC, Dartiguenave F, Burruni R, Tawadros T, Valerio M, Lucca I, Nardelli-Haefliger D, et al. Double positive CD4(+)CD8(+) T cells are enriched in urological cancers and favor T Helper-2 polarization. Front Immunol. 2019;10:622.CrossRef
21.
go back to reference Knutson KL, MJCI D. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother. 2005;54(8):721–8.CrossRef Knutson KL, MJCI D. Tumor antigen-specific T helper cells in cancer immunity and immunotherapy. Cancer Immunol Immunother. 2005;54(8):721–8.CrossRef
22.
go back to reference Khazaie K, Blatner NR, Khan MW, Gounari F, Gounaris E, Dennis K, Bonertz A, Tsai F-N, Strouch MJ, EJC C, et al. The significant role of mast cells in cancer. Cancer Metastasis Rev. 2011;30(1):45–60.CrossRef Khazaie K, Blatner NR, Khan MW, Gounari F, Gounaris E, Dennis K, Bonertz A, Tsai F-N, Strouch MJ, EJC C, et al. The significant role of mast cells in cancer. Cancer Metastasis Rev. 2011;30(1):45–60.CrossRef
23.
go back to reference Theoharides TC, Conti P. Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 2004;25(5):235–41.CrossRef Theoharides TC, Conti P. Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 2004;25(5):235–41.CrossRef
24.
go back to reference Zhang W, Pan Y, Gou P, Zhou C, Ma L, Liu Q, Du Y, Yang J, Wang Q. Effect of xanthohumol on Th1/Th2 balance in a breast cancer mouse model. Oncol Rep. 2018;39(1):280–8.PubMed Zhang W, Pan Y, Gou P, Zhou C, Ma L, Liu Q, Du Y, Yang J, Wang Q. Effect of xanthohumol on Th1/Th2 balance in a breast cancer mouse model. Oncol Rep. 2018;39(1):280–8.PubMed
25.
go back to reference Melssen M, Slingluff CL Jr. Vaccines targeting helper T cells for cancer immunotherapy. Curr Opin Immunol. 2017;47:85–92.CrossRef Melssen M, Slingluff CL Jr. Vaccines targeting helper T cells for cancer immunotherapy. Curr Opin Immunol. 2017;47:85–92.CrossRef
26.
go back to reference Kirkin AF, Dzhandzhugazyan KN, Guldberg P, Fang JJ, Andersen RS, Dahl C, Mortensen J, Lundby T, Wagner A, Law I, et al. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nat Commun. 2018;9(1):785.CrossRef Kirkin AF, Dzhandzhugazyan KN, Guldberg P, Fang JJ, Andersen RS, Dahl C, Mortensen J, Lundby T, Wagner A, Law I, et al. Adoptive cancer immunotherapy using DNA-demethylated T helper cells as antigen-presenting cells. Nat Commun. 2018;9(1):785.CrossRef
27.
go back to reference Kataoka TR, Ueshima C, Hirata M, Minamiguchi S, Haga H. Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis. Int J Mol Sci. 2020;21:954. https://www.mdpi.com/1422-0067/21/3/954. Kataoka TR, Ueshima C, Hirata M, Minamiguchi S, Haga H. Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis. Int J Mol Sci. 2020;21:954. https://​www.​mdpi.​com/​1422-0067/​21/​3/​954.
28.
go back to reference Miyamoto T, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T. Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma. Exp Mol Pathol. 2011;91(2):563–8.CrossRef Miyamoto T, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T. Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma. Exp Mol Pathol. 2011;91(2):563–8.CrossRef
29.
go back to reference Liu MF, Jin T, Shen JH, Shen ZY, Zheng ZC, Zhang ZL, Xu LY, Li EM, Xu HX. NGAL and NGALR are frequently overexpressed in human gliomas and are associated with clinical prognosis. J Neuro-Oncol. 2011;104(1):119–27.CrossRef Liu MF, Jin T, Shen JH, Shen ZY, Zheng ZC, Zhang ZL, Xu LY, Li EM, Xu HX. NGAL and NGALR are frequently overexpressed in human gliomas and are associated with clinical prognosis. J Neuro-Oncol. 2011;104(1):119–27.CrossRef
30.
go back to reference Zhang Y, Fan Y, Mei Z. NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification. Cancer Epidemiol. 2012;36(5):e294–9.CrossRef Zhang Y, Fan Y, Mei Z. NGAL and NGALR overexpression in human hepatocellular carcinoma toward a molecular prognostic classification. Cancer Epidemiol. 2012;36(5):e294–9.CrossRef
31.
go back to reference Gomez-Chou SB, Swidnicka-Siergiejko AK, Badi N, Chavez-Tomar M, Lesinski GB, Bekaii-Saab T, Farren MR, Mace TA, Schmidt C, Liu Y, et al. Lipocalin-2 promotes pancreatic ductal adenocarcinoma by regulating inflammation in the tumor microenvironment. Cancer Res. 2017;77(10):2647–60.CrossRef Gomez-Chou SB, Swidnicka-Siergiejko AK, Badi N, Chavez-Tomar M, Lesinski GB, Bekaii-Saab T, Farren MR, Mace TA, Schmidt C, Liu Y, et al. Lipocalin-2 promotes pancreatic ductal adenocarcinoma by regulating inflammation in the tumor microenvironment. Cancer Res. 2017;77(10):2647–60.CrossRef
Metadata
Title
Identification of immune cells and mRNA associated with prognosis of gastric cancer
Authors
Mingming Wang
Zedong Li
Yu Peng
Jianyu Fang
Tao Fang
Jiajia Wu
Jun Zhou
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2020
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-020-6702-1

Other articles of this Issue 1/2020

BMC Cancer 1/2020 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine