PARProceedings of Anticancer Research2208-35452208-3553Bio-Byword Scientific Publishing Pty. Ltd.10.26689/par.v6i2.3714ArticleGenomic Signature for the Prognosis of Survival in Relation to the Tumor Microenvironment in Esophageal Adenocarcinomahttps://artdesignp.com/journal/PAR/6/2/10.26689/par.v6i2.3714QinYi,TaoMinxian,SongLili,QianWeihua,GaoHaijian,LiuLianfang,ZhangYonghua,PanYingying2022622022-03-23Objective: To establish a new genomic signature for the prognosis of survival in relation to the tumor microenvironment in esophageal adenocarcinoma. Methods: Data from The Cancer Genome Atlas (TCGA) were applied, and the stromal and immune scores of patients with esophageal adenocarcinoma (EAC) were generated through the ESTIMATE algorithm. Differentially expressed genes were obtained, and genes concerning immune prognosis were identified on the basis of these scores. Functional analysis showed that these genes were primarily involved in immunobiological processes. Additionally, CIBERSORT was used to analyze 22 subgroups of tumor-infiltrating immune cells in the tumor microenvironment. Results: The results of the genomic assessment shown on the Kaplan-Meier curve revealed that EAC patients with high-risk scores have the worst survival. The risk score is valid as an independent prognostic factor for the overall survival in EAC patients. The tumor microenvironment was systematically analyzed, and the immune-related prognostic biomarkers of EAC have been proposed. Conclusion: The expression of tumor-infiltrating immune cells and immune-related genes in EAC have been identified. Some previously overlooked genes may be used as additional biomarkers for EAC in the future.

Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68(6): 394-424.

Ho ALK, Smyth EC, 2020, A Global Perspective on Oesophageal Cancer: Two Diseases in One. The Lancet Gastroenterology & Hepatology, 5(6): 521-522.

Short MW, Burgers KG, Fry VT, 2017, Esophageal Cancer. American Family Physician, 95(1): 22.

Hanahan D, Weinberg RA, 2000, The Hallmarks of Cancer, 100(1): 0-70.

Hanahan D, Coussens LM, 2012, Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment. Cancer Cell, 21(3): 309-322.

Jiang X, Wang J, Deng X, et al., 2019, Role of the Tumor Microenvironment in PD-L1/PD-1-Mediated Tumor Immune Escape. Molecular Cancer, 18(1): 1-17.

Yoshihara K, Shahmoradgoli M, Martinez E, et al., 2013, Inferring tumour Purity and Stromal and Immune Cell Admixture from Expression Data. Nat Commun, 4: 2612.

Jia D, Li S, Li D, et al., 2018, Mining TCGA Database for Genes of Prognostic Value in Glioblastoma Microenvironment. Aging (Albany NY), 10(4): 592.

Shah N, Wang P, Wongvipat J, et al., 2017, Regulation of the Glucocorticoid Receptor Via a BET-Dependent Enhancer Drives Antiandrogen Resistance in Prostate Cancer. Elife, 6: e27861.

Alonso MH, Ausso S, Lopez-Doriga A, et al., 2017, Comprehensive Analysis of Copy Number Aberrations in Microsatellite Stable Colon Cancer in View of Stromal Component. British Journal of Cancer, 117(3): 421-431.

Ritchie ME, Phipson B, Wu D, et al., 2015, Limma Powers Differential Expression Analyses for RNA-Sequencing and Microarray Studies. Nucleic Acids Res, 43(7): e47.

Zhou Y, Zhou B, Pache L, et al., 2019, Metascape Provides a Biologist-Oriented Resource for the Analysis of Systems-Level Datasets. Nat Commun, 10(1): 1523.

Shahraki HR, Salehi A, Zare N, 2015, Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach. Asian Pac J Cancer Prev, 16(15): 6773-6777.

Newman AM, Liu CL, Green MR, et al., 2015, Robust Enumeration of Cell Subsets from Tissue Expression Profiles. Nature Methods, 12(5): 453-457.

Lin EW, Karakasheva TA, Hicks PD, et al., 2016, The Tumor Microenvironment in Esophageal Cancer. Oncogene, 35(41): 5337-5349.

Matsushita M, Endo Y, Fujita T, 1998, MASP1 (MBL-Associated Serine Protease 1). Immunobiology, 199(2): 340-347.

Swierzko AS, Szala A, Sawicki S, et al., 2014, Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours. Cancer Immunol Immunother, 2014. 63(11): p. 1129-40.

Ytting H, Christensen IJ, Steffensen R, et al., 2011, Mannan-Binding Lectin (MBL) and MBL-Associated Serine Protease 2 (MASP-2) Genotypes in Colorectal Cancer. Scand J Immunol, 73(2): 122-127.

Maestri CA, Nisihara R, Mendes HW, et al., 2018, MASP-1 and MASP-2 Serum Levels Are Associated with Worse Prognostic in Cervical Cancer Progression. Front Immunol, 9: 2742.

Losi CG, Silini A, Fiorini C, et al., 2005, Mutational Analysis of Human BAFF Receptor TNFRSF13C (BAFF-R) in Patients with Common Variable Immunodeficiency. J Clin Immunol, 25(5): 496-502.

Pham LV, Fu L, Tamayo AT, et al., 2011, Constitutive BR3 Receptor Signaling in Diffuse, Large B-Cell Lymphomas Stabilizes Nuclear Factor-Kappab-Inducing Kinase While Activating Both Canonical and Alternative Nuclear Factor-Kappab Pathways. Blood, 117(1): 200-210.

Parameswaran R, Muschen M, Kim Y-M, et al., 2010, A Functional Receptor for B-Cell-Activating Factor Is Expressed on Human Acute Lymphoblastic Leukemias. Cancer Res, 70(11): 4346-4356.

Kern C, Cornuel J-F, Billard C, et al., 2004, Involvement of BAFF and APRIL in the Resistance to Apoptosis of B-CLL through an Autocrine Pathway. Blood, 103(2): 679-688.

Endo T, Nishio M, Enzler T, et al., 2007, BAFF and APRIL Support Chronic Lymphocytic Leukemia B-Cell Survival through Activation of the Canonical NF-Kappab Pathway. Blood, 109(2): 703-710.

Suliman BA, Xu D, Williams BRG, 2012, The Promyelocytic Leukemia Zinc Finger Protein: Two Decades of Molecular Oncology. Frontiers in Oncology, 2: 74.

Kolesnichenko M, Vogt PK, 2011, Understanding PLZF: Two Transcriptional Targets, REDD1 and Smooth Muscle ?-Actin, Define New Questions in Growth Control, Senescence, Self-Renewal and Tumor Suppression. Cell Cycle, 10(5): 771-775.

Cheung M, Pei J, Pei Y, et al., 2010, The Promyelocytic Leukemia Zinc-Finger Gene, PLZF, Is Frequently Downregulated in Malignant Mesothelioma Cells and Contributes to Cell Survival. Oncogene, 29(11): 1633-1640.

Topalian SL, Hodi FS, Brahmer JR, et al., 2012, Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. New England Journal of Medicine, 366(26): 2443-2454.

Brown SD, Warren RL, Gibb EA, et al., 2014, Neo-Antigens Predicted by Tumor Genome Meta-Analysis Correlate with Increased Patient Survival. Genome Research, 24(5): 743-750.

Zheng X, Song X, Shao Y, et al., 2018, Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: A Meta-Analysis. Cell Physiol Biochem, 45(2): 720-732.

Tan LY, Martini C, Fridlender ZG, et al., 2017, Control of Immune Cell Entry through the Tumour Vasculature: A Missing Link in Optimising Melanoma Immunotherapy?. Clinical & Translational Immunology, 6(3): e134.

Zingg U, Montani M, Frey DM, et al., 2010, Tumour-Infiltrating Lymphocytes and Survival in Patients with Adenocarcinoma of the Oesophagus. European Journal of Surgical Oncology, 36(7): 670-677.

Schreiber RD, Old LJ, Smyth MJ, Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion. Science, 331(6024): 1565-1570.

Linsley PS, Chaussabel D, Speake C, 2015, The Relationship of Immune Cell Signatures to Patient Survival Varies Within and Between Tumor Types. PLoS One, 10(9): e0138726.

Chen K, Zhu Z, Zhang N, et al., 2017, Tumor-Infiltrating CD4+ Lymphocytes Predict a Favorable Survival in Patients with Operable Esophageal Squamous Cell Carcinoma. Medical Science Monitor, 23: 4619-4632.

Kavanagh ME, Conroy MJ, Clarke NE, et al., 2016, Impact of the Inflammatory Microenvironment on T-Cell Phenotype in the Progression from Reflux Oesophagitis to Barrett Oesophagus and Oesophageal Adenocarcinoma. Cancer Lett, 370(1): 117-124.

Sarvaria A, Madrigal JA, Saudemont A, 2017, B Cell Regulation in Cancer and Anti-Tumor Immunity. Cell Mol Immunol, 14(8): 662-674.