Identification of a novel immune-related prognostic signature of breast cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YU Xin ¹ ,  SUN Shengrong ¹ ,  WANG Weixing ²

1. Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;
2. Department of Hepatobiliary Surgery, Renmin Hospital of Wuhan University, Wuhan 430060, P. R. China;

Corresponding author：

SUN Shengrong, Email: sun137@sina.com; WANG Weixing, Email: sate.llite@163.com

Keywords：

breast cancer; immune signature; overall survival

DOI：

10.7507/1007-9424.202103106

Video：

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Objective To explore the immune biomarkers for prognosis of breast cancer and to construct a risk assessment model.Methods The gene expression of breast cancer samples was retrieved from The Cancer Genome Map (TCGA) database and immune related genes (IRGs) were retrieved from the ImmPort database. Cox proportional hazards regression and least absolute shrinkage and selection operator (LASSO) regression were used for prognostic analysis. Gene set enrichment analysis ( GSEA) was used to explore biological signaling pathways. ESTIMATE and CIBERSORT algorithms were used to explore the relationship between risk score and tumor immune microenvironment.Results Nine kinds of immune-related differentially expressed genes independently related to prognosis were identified: adrenoceptor beta 1 (ADRB1), interleukin 12B (IL12B), syndecan 1 (SDC1), thymic stromal lymphopoietin (TSLP), fibroblast growth factor 19 (FGF19), fatty acid binding protein 7 (FABP7), interferon epsilon (IFNE), tumor necrosis factor receptor superfamily member 18 (TNFRSF18) and interleukin 27 (IL27). The risk assessment equation constructed by these nine kinds of genes had powerful predictive ability. The “neurotrophin signaling pathway” and “adipocyte factor signaling pathway” were activated in patients of high-risk group, and “leukocyte transendothelial migration” “WNT signaling pathway” “FcεRI signaling pathway” “valine, leucine and isoleucine biosynthesis” and “protein export pathway” were activated in patients of low-risk group. A variety of tumor-killing immune cells were significantly enriched in the tumor-infiltrating immune cells of patients in the low-risk group. The immunosuppressive immune cells were significantly enriched in tumor infiltrating immune cells of patients in high-risk group.Conclusion IRGs prognostic signatures are an effective potential predictive classifier in breast cancer treatment.

Citation： YU Xin, SUN Shengrong, WANG Weixing. Identification of a novel immune-related prognostic signature of breast cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2021, 28(12): 1612-1618. doi: 10.7507/1007-9424.202103106 Copy

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21.	Shi S, Zhong D, Xiao Y, et al. Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway. Oncotarget, 2017, 8(25): 40922-40934.
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33.	Lu D, Zhou X, Yao L, et al. Clinical implications of the interleukin 27 serum level in breast cancer. J Investig Med, 2014, 62(3): 627-631.
34.	Xie P, Ma Y, Yu S, et al. Development of an immune-related prognostic signature in breast cancer. Front Genet, 2020, 10: 1390.
35.	Xu W, Qian J, Zeng F, et al. Protein kinase Ds promote tumor angiogenesis through mast cell recruitment and expression of angiogenic factors in prostate cancer microenvironment. J Exp Clin Cancer Res, 2019, 38(1): 114.
36.	Sammarco G, Varricchi G, Ferraro V, et al. Mast cells, angiogenesis and lymphangiogenesis in human gastric cancer. Int J Mol Sci, 2019, 20(9): 2106.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Soysal SD, Tzankov A, Muenst SE. Role of the tumor microenvironment in breast cancer. Pathobiology, 2015, 82(3-4): 142-152.
3. Choi J, Gyamfi J, Jang H, et al. The role of tumor-associated macrophage in breast cancer biology. Histol Histopathol, 2018, 33(2): 133-145.
4. Lim B, Woodward WA, Wang X, et al. Inflammatory breast cancer biology: the tumour microenvironment is key. Nat Rev Cancer, 2018, 18(8): 485-499.
5. Wu Q, Li J, Li Z, et al. Exosomes from the tumour-adipocyte interplay stimulate beige/brown differentiation and reprogram metabolism in stromal adipocytes to promote tumour progression. J Exp Clin Cancer Res, 2019, 38(1): 223.
6. Emens LA. Breast cancer immunotherapy: facts and hopes. Clin Cancer Res, 2018, 24(3): 511-520.
7. Emens LA. Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade. Expert Rev Anticancer Ther, 2012, 12(12): 1597-1611.
8. Shi T, Ma Y, Yu L, et al. Cancer immunotherapy: a focus on the regulation of immune checkpoints. Int J Mol Sci, 2018, 19(5): 1389.
9. Basu A, Ramamoorthi G, Jia Y, et al. Immunotherapy in breast cancer: current status and future directions. Adv Cancer Res, 2019, 143: 295-349.
10. Gasser S, Lim LHK, Cheung FSG. The role of the tumour microenvironment in immunotherapy. Endocr Relat Cancer, 2017, 24(12): T283-T295.
11. 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, 2017, 18(1): 248-262.
12. Liu J, Meng H, Nie S, et al. Identification of a prognostic signature of epithelial ovarian cancer based on tumor immune microenvironment exploration. Genomics, 2020, 112(6): 4827-4841.
13. Song Q, Shang J, Yang Z, et al. Identification of an immune signature predicting prognosis risk of patients in lung adenocarcinoma. J Transl Med, 2019, 17(1): 70.
14. Kelley EF, Snyder EM, Johnson BD. Influence of beta-1 adrenergic receptor genotype on cardiovascular response to exercise in healthy subjects. Cardiol Res, 2018, 9(6): 343-349.
15. Işeri OD, Sahin FI, Terzi YK, et al. Beta-adrenoreceptor antagonists reduce cancer cell proliferation, invasion, and migration. Pharm Biol, 2014, 52(11): 1374-1381.
16. Wang J, Zhang X, Li J, et al. ADRB1 was identified as a potential biomarker for breast cancer by the co-analysis of tumor mutational burden and immune infiltration. Aging (Albany NY), 2020, 13(1): 351-363.
17. Yan J, Smyth MJ, Teng MWL. Interleukin (IL)-12 and IL-23 and their conflicting roles in cancer. Cold Spring Harb Perspect Biol, 2018, 10(7): a028530.
18. Sun R, Jia F, Liang Y, et al. Interaction analysis of IL-12A and IL-12B polymorphisms with the risk of colorectal cancer. Tumour Biol, 2015, 36(12): 9295-9301.
19. Kaarvatn MH, Vrbanec J, Kulic A, et al. Single nucleotide polymorphism in the interleukin 12B gene is associated with risk for breast cancer development. Scand J Immunol, 2012, 76(3): 329-335.
20. Chen X, Han S, Wang S, et al. Interactions of IL-12A and IL-12B polymorphisms on the risk of cervical cancer in Chinese women. Clin Cancer Res, 2009, 15(1): 400-405.
21. Shi S, Zhong D, Xiao Y, et al. Syndecan-1 knockdown inhibits glioma cell proliferation and invasion by deregulating a c-src/FAK-associated signaling pathway. Oncotarget, 2017, 8(25): 40922-40934.
22. Cui X, Jing X, Yi Q, et al. Clinicopathological and prognostic significance of SDC1 overexpression in breast cancer. Oncotarget, 2017, 8(67): 111444-111455.
23. Ziegler SF, Artis D. Sensing the outside world: TSLP regulates barrier immunity. Nat Immunol, 2010, 11(4): 289-293.
24. Kuan EL, Ziegler SF. A tumor-myeloid cell axis, mediated via the cytokines IL-1α and TSLP, promotes the progression of breast cancer. Nat Immunol, 2018, 19(4): 366-374.
25. Liu Y, Cao M, Cai Y, et al. Dissecting the role of the FGF19-FGFR4 signaling pathway in cancer development and progression. Front Cell Dev Biol, 2020, 8: 95.
26. Sawey ET, Chanrion M, Cai C, et al. Identification of a therapeutic strategy targeting amplified FGF19 in liver cancer by Oncogenomic screening. Cancer Cell, 2011, 19(3): 347-358.
27. Kagawa Y, Umaru BA, Ariful I, et al. Role of FABP7 in tumor cell signaling. Adv Biol Regul, 2019, 71: 206-218.
28. Ma R, Wang L, Yuan F, et al. FABP7 promotes cell proliferation and survival in colon cancer through MEK/ERK signaling pathway. Biomed Pharmacother, 2018, 108: 119-129.
29. Cordero A, Kanojia D, Miska J, et al. FABP7 is a key metabolic regulator in HER2⁺ breast cancer brain metastasis. Oncogene, 2019, 38(37): 6445-6460.
30. Vence L, Bucktrout SL, Fernandez Curbelo I, et al. Charac-terization and comparison of GITR expression in solid tumors. Clin Cancer Res, 2019, 25(21): 6501-6510.
31. Buzzatti G, Dellepiane C, Del Mastro L. New emerging targets in cancer immunotherapy: the role of GITR. ESMO Open, 2020, 4(Suppl 3): e000738.
32. Fabbi M, Carbotti G, Ferrini S. Dual roles of IL-27 in cancer biology and immunotherapy. Mediators Inflamm, 2017, 2017: 3958069.
33. Lu D, Zhou X, Yao L, et al. Clinical implications of the interleukin 27 serum level in breast cancer. J Investig Med, 2014, 62(3): 627-631.
34. Xie P, Ma Y, Yu S, et al. Development of an immune-related prognostic signature in breast cancer. Front Genet, 2020, 10: 1390.
35. Xu W, Qian J, Zeng F, et al. Protein kinase Ds promote tumor angiogenesis through mast cell recruitment and expression of angiogenic factors in prostate cancer microenvironment. J Exp Clin Cancer Res, 2019, 38(1): 114.
36. Sammarco G, Varricchi G, Ferraro V, et al. Mast cells, angiogenesis and lymphangiogenesis in human gastric cancer. Int J Mol Sci, 2019, 20(9): 2106.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Identification of a novel immune-related prognostic signature of breast cancer

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