A Prognostic Model Based on the Immune-related Genes in Colon Adenocarcinoma

被引:28
作者
Sun, Yuan-Lin [1 ]
Zhang, Yang [1 ]
Guo, Yu-Chen [1 ]
Yang, Zi-Hao [1 ]
Xu, Yue-Chao [1 ]
机构
[1] Jilin Univ, Dept Gastrointestinal Surg, Hosp 1, Changchun 130021, Jilin, Peoples R China
关键词
immune-related genes (IRGs); differential expressed analysis; prognostic model; Cox regression analysis; colon adenocarcinoma (COAD); COLORECTAL-CANCER; BREAST-CANCER; COMPREHENSIVE ANALYSIS; CELL-MIGRATION; T-CELLS; EXPRESSION; IDENTIFICATION; SIGNATURE; SURVIVAL; MARKER;
D O I
10.7150/ijms.45813
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Immune-related genes (IRGs) are critically involved in the tumor microenvironment (TME) of colon adenocarcinoma (COAD). Here, the study was mainly designed to establish a prognostic model of IRGs to predict the survival of COAD patients. Methods: The Cancer Genome Atlas (TCGA), Immunology Database and Analysis Portal (ImmPort) database, and Cistrome database were utilized for extracting data regarding the expression of immune gene- and tumor-related transcription factors (TFs), aimed at the identification of differentially expressed genes (DEGs), differentially expressed IRGs (DEIRGs), and differentially expressed TFs (DETFs). Univariate Cox regression analysis was subsequently performed for the acquisition of prognosis-related IRGs, followed by establishment of TF regulatory network for uncovering the possible molecular regulatory association in COAD. Subsequently, multivariate Cox regression analysis was conducted to further determine the role of prognosis-related IRGs for prognostic prediction in COAD. Finally, the feasibility of a prognostic model with immunocytes was explored by immunocyte infiltration analysis. Results: A total of 2450 DEGs, 8 DETFs, and 79 DEIRGs were extracted from the corresponding databases. Univariate Cox regression analysis revealed 11 prognosis-related IRGs, followed by establishment of a regulatory network on prognosis-related IRGs at transcriptional levels. Functionally, IRG GLP2R was negatively modulated by TF MYH11, whereas IRG TDGF1 was positively modulated by TF TFAP2A. Multivariate Cox regression analysis was subsequently performed to establish a prognostic model on the basis of seven prognosis-related IRGs (GLP2R, ESM1, TDGF1, SLC10A2, INHBA, STC2, and CXCL1). Moreover, correlation analysis of immunocyte infiltration also revealed that the seven-IRG prognostic model was positively associated with five types of immunocytes (dendritic cell, macrophage, CD4 T cell, CD8 T cell, and neutrophil), which may directly reflect tumor immune state in COAD. Conclusions: Our present findings indicate that the prognostic model based on prognosis-related IRGs plays a crucial role in the clinical supervision and prognostic prediction of COAD patients at both molecular and cellular levels.
引用
收藏
页码:1879 / 1896
页数:18
相关论文
共 63 条
[1]   Global patterns and trends in colorectal cancer incidence and mortality [J].
Arnold, Melina ;
Sierra, Monica S. ;
Laversanne, Mathieu ;
Soerjomataram, Isabelle ;
Jemal, Ahmedin ;
Bray, Freddie .
GUT, 2017, 66 (04) :683-691
[2]   Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization [J].
Aymeric, Laetitia ;
Donnadieu, Francoise ;
Mulet, Celine ;
du Merle, Laurence ;
Nigro, Giulia ;
Saffarian, Azadeh ;
Berard, Marion ;
Poyart, Claire ;
Robine, Sylvie ;
Regnault, Beatrice ;
Trieu-Cuot, Patrick ;
Sansonetti, Philippe J. ;
Dramsi, Shaynoor .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (02) :E283-E291
[3]   Restoring function in exhausted CD8 T cells during chronic viral infection [J].
Barber, DL ;
Wherry, EJ ;
Masopust, D ;
Zhu, BG ;
Allison, JP ;
Sharpe, AH ;
Freeman, GJ ;
Ahmed, R .
NATURE, 2006, 439 (7077) :682-687
[4]   ImmPort, toward repurposing of open access immunological assay data for translational and clinical research [J].
Bhattacharya, Sanchita ;
Dunn, Patrick ;
Thomas, Cristel G. ;
Smith, Barry ;
Schaefer, Henry ;
Chen, Jieming ;
Hu, Zicheng ;
Zalocusky, Kelly A. ;
Shankar, Ravi D. ;
Shen-Orr, Shai S. ;
Thomson, Elizabeth ;
Wiser, Jeffrey ;
Butte, Atul J. .
SCIENTIFIC DATA, 2018, 5
[5]   CXCL2/CXCR2 axis induces cancer stem cell characteristics in CPT-11-resistant LoVo colon cancer cells via Gi-2 and Gq/11 [J].
Chen, Ming-Cheng ;
Baskaran, Rathinasamy ;
Lee, Nien-Hung ;
Hsu, Hsi-Hsien ;
Ho, Tsung-Jung ;
Tu, Chuan-Chou ;
Lin, Yueh-Min ;
Viswanadha, Vijaya Padma ;
Kuo, Wei-Wen ;
Huang, Chih-Yang .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (07) :11822-11834
[6]   Interleukin-17 Induces CC Chemokine Receptor 6 Expression and Cell Migration in Colorectal Cancer Cells [J].
Chin, Chih-Chien ;
Chen, Cheng-Nan ;
Kuo, Hsing-Chun ;
Shi, Chung-Sheng ;
Hsieh, Meng Chiao ;
Kuo, Yi-Hung ;
Tung, Shui-Yi ;
Lee, Kam-Fai ;
Huang, Wen-Shih .
JOURNAL OF CELLULAR PHYSIOLOGY, 2015, 230 (07) :1430-1437
[7]   An atlas of transposable element-derived alternative splicing in cancer [J].
Clayton, Evan A. ;
Rishishwar, Lavanya ;
Huang, Tzu-Chuan ;
Gulati, Saurabh ;
Ban, Dongjo ;
McDonald, John F. ;
Jordan, I. King .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 2020, 375 (1795)
[8]   CDX2 as a Prognostic Biomarker in Stage II and Stage III Colon Cancer [J].
Dalerba, Piero ;
Sahoo, Debashis ;
Paik, Soonmyung ;
Guo, Xiangqian ;
Yothers, Greg ;
Song, Nan ;
Wilcox-Fogel, Nate ;
Forgo, Erna ;
Rajendran, Pradeep S. ;
Miranda, Stephen P. ;
Hisamori, Shigeo ;
Hutchison, Jacqueline ;
Kalisky, Tomer ;
Qian, Dalong ;
Wolmark, Norman ;
Fisher, George A. ;
van de Rijn, Matt ;
Clarke, Michael F. .
NEW ENGLAND JOURNAL OF MEDICINE, 2016, 374 (03) :211-222
[9]   Inhibition of breast cancer cell migration by activation of cAMP signaling [J].
Dong, Hongli ;
Claffey, Kevin P. ;
Brocke, Stefan ;
Epstein, Paul M. .
BREAST CANCER RESEARCH AND TREATMENT, 2015, 152 (01) :17-28
[10]   Pentoxifylline impedes migration in B16F10 melanoma by modulating Rho GTPase activity and actin organisation [J].
Dua, Pooja ;
Gude, Rajiv P. .
EUROPEAN JOURNAL OF CANCER, 2008, 44 (11) :1587-1595