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Cancer Cell International
Published in: Cancer Cell International 1/2020

01-12-2020 | Endometrial Cancer | Primary research

Identification of an immune gene signature for predicting the prognosis of patients with uterine corpus endometrial carcinoma

Authors: Cankun Zhou, Chaomei Li, Fangli Yan, Yuhua Zheng

Published in: Cancer Cell International | Issue 1/2020

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Abstract

Background

Uterine corpus endometrial carcinoma (UCEC) is a frequent gynecological malignancy with a poor prognosis particularly at an advanced stage. Herein, this study aims to construct prognostic markers of UCEC based on immune-related genes to predict the prognosis of UCEC.

Methods

We analyzed expression data of 575 UCEC patients from The Cancer Genome Atlas database and immune genes from the ImmPort database, which were used for generation and validation of the signature. We constructed a transcription factor regulatory network based on Cistrome databases, and also performed functional enrichment and pathway analyses for the differentially expressed immune genes. Moreover, the prognostic value of 410 immune genes was determined using the Cox regression analysis. We then constructed and verified a prognostic signature. Finally, we performed immune infiltration analysis using TIMER-generating immune cell content.

Results

The immune cell microenvironment as well as the PI3K-Akt, and MARK signaling pathways were involved in UCEC development. The established prognostic signature revealed a ten-gene prognostic signature, comprising of PDIA3, LTA, PSMC4, TNF, SBDS, HDGF, HTR3E, NR3C1, PGR, and CBLC. This signature showed a strong prognostic ability in both the training and testing sets and thus can be used as an independent tool to predict the prognosis of UCEC. In addition, levels of B cells and neutrophils were significantly correlated with the patient’s risk score, while the expression of ten genes was associated with immune cell infiltrates.

Conclusions

In summary, the ten-gene prognostic signature may guide the selection of the immunotherapy for UCEC.
Appendix
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Literature
1.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 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.CrossRefPubMed
2.
Lee YC, Lheureux S, Oza AM. Treatment strategies for endometrial cancer: current practice and perspective. Curr Opin Obstet Gynecol. 2017;29(1):47–58.CrossRefPubMed
3.
Pitt JM, Marabelle A, Eggermont A, Soria JC, Kroemer G, Zitvogel L. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol. 2016;27(8):1482–92.CrossRefPubMed
4.
Najafi M, Goradel NH, Farhood B, Salehi E, Solhjoo S, Toolee H, Kharazinejad E, Mortezaee K. Tumor microenvironment: interactions and therapy. J Cell Physiol. 2019;234(5):5700–21.CrossRefPubMed
5.
Murata T, Mizushima H, Chinen I, Moribe H, Yagi S, Hoffman RM, Kimura T, Yoshino K, Ueda Y, Enomoto T, et al. HB-EGF and PDGF mediate reciprocal interactions of carcinoma cells with cancer-associated fibroblasts to support progression of uterine cervical cancers. Cancer Res. 2011;71(21):6633–42.CrossRefPubMed
6.
7.
Modugno F, Ness RB, Chen C, Weiss NS. Inflammation and endometrial cancer: a hypothesis. Cancer Epidemiol Biomark Prev. 2005;14(12):2840–7.CrossRef
8.
Holub K, Biete A. New pre-treatment eosinophil-related ratios as prognostic biomarkers for survival outcomes in endometrial cancer. BMC Cancer. 2018;18(1):1280.CrossRefPubMedPubMedCentral
9.
Walentowicz-Sadlecka M, Sadlecki P, Bodnar M, Marszalek A, Walentowicz P, Sokup A, Wilinska-Jankowska A, Grabiec M. Stromal derived factor-1 (SDF-1) and its receptors CXCR4 and CXCR7 in endometrial cancer patients. PLoS ONE. 2014;9(1):e84629.CrossRefPubMedPubMedCentral
10.
Felix AS, Stone RA, Chivukula M, Bowser R, Parwani AV, Linkov F, Edwards RP, Weissfeld JL. Survival outcomes in endometrial cancer patients are associated with CXCL12 and estrogen receptor expression. Int J Cancer. 2012;131(2):E114–21.CrossRefPubMedPubMedCentral
11.
Zhang W, Hou F, Zhang Y, Tian Y, Jiao J, Ma D, Kong B, Cui B. Changes of Th17/Tc17 and Th17/Treg cells in endometrial carcinoma. Gynecol Oncol. 2014;132(3):599–605.CrossRefPubMed
12.
Muhammad N, Steele R, Isbell TS, Philips N, Ray RB. Bitter melon extract inhibits breast cancer growth in preclinical model by inducing autophagic cell death. Oncotarget. 2017;8(39):66226–36.CrossRefPubMedPubMedCentral
13.
Van Nyen T, Moiola CP, Colas E, Annibali D, Amant F. Modeling endometrial cancer: past, present, and future. Int J Mol Sci. 2018;19(8):2348.CrossRefPubMedCentral
14.
Bhattacharya S, Dunn P, Thomas CG, Smith B, Schaefer H, Chen J, Hu Z, Zalocusky KA, Shankar RD, Shen-Orr SS, et al. ImmPort, toward repurposing of open access immunological assay data for translational and clinical research. Sci Data. 2018;5:180015.CrossRefPubMedPubMedCentral
15.
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7):e47.CrossRefPubMedPubMedCentral
16.
Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C, Zhu M, Wu J, Shi X, Taing L, et al. Cistrome data browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Res. 2017;45(D1):D658–D662.CrossRefPubMed
17.
Li T, Fan J, Wang B, Traugh N, Chen Q, Liu JS, Li B, Liu XS. TIMER: a web server for comprehensive analysis of tumor-infiltrating immune cells. Cancer Res. 2017;77(21):e108–10.CrossRefPubMedPubMedCentral
18.
Van Gool IC, Stelloo E, Nout RA, Nijman HW, Edmondson RJ, Church DN, MacKay HJ, Leary A, Powell ME, Mileshkin L, et al. Prognostic significance of L1CAM expression and its association with mutant p53 expression in high-risk endometrial cancer. Mod Pathol. 2016;29(2):174–81.CrossRefPubMed
19.
Zheng F, Yu H, Lu J. High expression of MUC20 drives tumorigenesis and predicts poor survival in endometrial cancer. J Cell Biochem. 2019;120(7):11859–66.CrossRef
20.
Ying J, Wang Q, Xu T, Lyu J. Establishment of a nine-gene prognostic model for predicting overall survival of patients with endometrial carcinoma. Cancer Med. 2018;7(6):2601–11.CrossRefPubMedPubMedCentral
21.
Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501(7467):346–54.CrossRefPubMed
22.
Chen HX, Xu XX, Tan BZ, Zhang Z, Zhou XD. MicroRNA-29b Inhibits Angiogenesis by Targeting VEGFA through the MAPK/ERK and PI3K/Akt Signaling Pathways in Endometrial Carcinoma. Cell Physiol Biochem. 2017;41(3):933–46.CrossRefPubMed
23.
Wang J, Sun X, Zhang H, Wang Y, Li Y. MPA influences tumor cell proliferation, migration, and invasion induced by RANKL through PRB involving the MAPK pathway in endometrial cancer. Oncol Rep. 2015;33(2):799–809.CrossRefPubMed
24.
Chiu HC, Li CJ, Yiang GT, Tsai AP, Wu MY. Epithelial to mesenchymal transition and cell biology of molecular regulation in endometrial carcinogenesis. J Clin Med. 2019;8(4):439.CrossRefPubMedCentral
25.
Subramaniam KS, Omar IS, Kwong SC, Mohamed Z, Woo YL, Mat Adenan NA, Chung I. Cancer-associated fibroblasts promote endometrial cancer growth via activation of interleukin-6/STAT-3/c-Myc pathway. Am J Cancer Res. 2016;6(2):200–13.PubMedPubMedCentral
26.
27.
Chuwa AH, Sone K, Oda K, Ikeda Y, Fukuda T, Wada-Hiraike O, Inaba K, Makii C, Takeuchi M, Oki S, et al. Significance of survivin as a prognostic factor and a therapeutic target in endometrial cancer. Gynecol Oncol. 2016;141(3):564–9.CrossRefPubMed
28.
Vanderstraeten A, Everaert T, Van Bree R, Verbist G, Luyten C, Amant F, Tuyaerts S. In vitro validation of survivin as target tumor-associated antigen for immunotherapy in uterine cancer. J Immunother. 2015;38(6):239–49.CrossRefPubMed
29.
Tsai HE, Liu GS, Kung ML, Liu LF, Wu JC, Tang CH, Huang CH, Chen SC, Lam HC, Wu CS, et al. Downregulation of hepatoma-derived growth factor contributes to retarded lung metastasis via inhibition of epithelial-mesenchymal transition by systemic POMC gene delivery in melanoma. Mol Cancer Ther. 2013;12(6):1016–25.CrossRefPubMed
30.
Wang S, Fang W. Increased expression of hepatoma-derived growth factor correlates with poor prognosis in human nasopharyngeal carcinoma. Histopathology. 2011;58(2):217–24.CrossRefPubMed
31.
Bao C, Wang J, Ma W, Wang X, Cheng Y. HDGF: a novel jack-of-all-trades in cancer. Future Oncol. 2014;10(16):2675–85.CrossRefPubMed
32.
Wang L, Jiang Q, Hua S, Zhao M, Wu Q, Fu Q, Fang W, Guo S. High nuclear expression of HDGF correlates with disease progression and poor prognosis in human endometrial carcinoma. Dis Markers. 2014;2014:298795.PubMedPubMedCentral
33.
34.
Kuang Y, Cai J, Li D, Han Q, Cao J, Wang Z. Repression of Dicer is associated with invasive phenotype and chemoresistance in ovarian cancer. Oncol Lett. 2013;5(4):1149–54.CrossRefPubMedPubMedCentral
35.
Muralidhar B, Goldstein LD, Ng G, Winder DM, Palmer RD, Gooding EL, Barbosa-Morais NL, Mukherjee G, Thorne NP, Roberts I, et al. Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels. J Pathol. 2007;212(4):368–77.CrossRefPubMed
36.
Morice P, Leary A, Creutzberg C, Abu-Rustum N, Darai E. Endometrial cancer. Lancet. 2016;387(10023):1094–108.CrossRefPubMed
37.
Shih TC, Tien YJ, Wen CJ, Yeh TS, Yu MC, Huang CH, Lee YS, Yen TC, Hsieh SY. MicroRNA-214 downregulation contributes to tumor angiogenesis by inducing secretion of the hepatoma-derived growth factor in human hepatoma. J Hepatol. 2012;57(3):584–91.CrossRefPubMed
38.
Hellwinkel OJ, Asong LE, Rogmann JP, Sültmann H, Wagner C, Schlomm T, Eichelberg C. Transcription alterations of members of the ubiquitin-proteasome network in prostate carcinoma. Prostate Cancer Prostat Dis. 2011;14(1):38–45.CrossRef
39.
Gately L, Collins A, Murphy M, Dowling A. Age alone is not a predictor for survival in glioblastoma. J Neurooncol. 2016;129(3):479–85.CrossRefPubMed
40.
Dossus L, Lukanova A, Rinaldi S, Allen N, Cust AE, Becker S, Tjonneland A, Hansen L, Overvad K, Chabbert-Buffet N, et al. Hormonal, metabolic, and inflammatory profiles and endometrial cancer risk within the EPIC cohort—a factor analysis. Am J Epidemiol. 2013;177(8):787–99.CrossRefPubMed
41.
Chu TH, Huang ST, Yang SF, Li CJ, Lin HW, Weng BC, Yang SM, Huang SC, Wu JC, Chang YC, et al. Hepatoma-derived growth factor participates in Helicobacter Pylori-induced neutrophils recruitment, gastritis and gastric carcinogenesis. Oncogene. 2019;38(37):6461–77.CrossRefPubMed
42.
Wikberg ML, Ling A, Li X, Öberg Å, Edin S, Palmqvist R. Neutrophil infiltration is a favorable prognostic factor in early stages of colon cancer. Hum Pathol. 2017;68:193–202.CrossRefPubMed
43.
Shimizu K, Okita R, Saisho S, Yukawa T, Maeda A, Nojima Y, Nakata M. Prognostic nutritional index before adjuvant chemotherapy predicts chemotherapy compliance and survival among patients with non-small-cell lung cancer. Ther Clin Risk Manag. 2015;11:1555–61.CrossRefPubMedPubMedCentral
44.
Kuang DM, Zhao Q, Wu Y, Peng C, Wang J, Xu Z, Yin XY, Zheng L. Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma. J Hepatol. 2011;54(5):948–55.CrossRefPubMed
45.
Schmidt M, Hellwig B, Hammad S, Othman A, Lohr M, Chen Z, Boehm D, Gebhard S, Petry I, Lebrecht A, et al. A comprehensive analysis of human gene expression profiles identifies stromal immunoglobulin κ C as a compatible prognostic marker in human solid tumors. Clin Cancer Res. 2012;18(9):2695–703.CrossRefPubMed
46.
47.
Nielsen JS, Sahota RA, Milne K, Kost SE, Nesslinger NJ, Watson PH, Nelson BH. CD20+ tumor-infiltrating lymphocytes have an atypical CD27− memory phenotype and together with CD8+ T cells promote favorable prognosis in ovarian cancer. Clin Cancer Res. 2012;18(12):3281–92.CrossRefPubMed
Metadata
Title
Identification of an immune gene signature for predicting the prognosis of patients with uterine corpus endometrial carcinoma
Authors
Cankun Zhou
Chaomei Li
Fangli Yan
Yuhua Zheng
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/s12935-020-01560-w

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