Construction of ceRNA Networks Associated With CD8 T Cells in Breast Cancer

被引:22
作者
Chen, Zhilin [1 ,2 ]
Feng, Ruifa [3 ]
Kahlert, Ulf Dietrich [4 ,6 ]
Chen, Zhitong [2 ]
Torres-dela Roche, Luz Angela [2 ]
Soliman, Amr [2 ]
Miao, Chen [5 ]
De Wilde, Rudy Leon [2 ]
Shi, Wenjie [2 ,4 ,6 ]
机构
[1] Hainan Med Univ, Dept Breast & Thorac Oncol Surg, Affiliated Hosp 1, Haikou, Peoples R China
[2] Univ Med Oldenburg, Univ Hosp Gynecol, Pius Hosp, Oldenburg, Germany
[3] Guilin Med Univ, Affiliated Hosp 2, Breast Ctr, Guilin, Peoples R China
[4] Univ Med Magdeburg, Univ Clin Gen Visceral & Vasc Surg, Mol & Expt Surg, Magdeburg, Germany
[5] Nanjing Med Univ, Dept Pathol, Affiliated Hosp 1, Nanjing, Peoples R China
[6] Otto von Guericke Univ, Magdeburg, Germany
关键词
ceRNA; T cell; breast cancer; lncRNA; target; PROLIFERATION; METASTASIS; PACKAGE; WOMEN;
D O I
10.3389/fonc.2022.883197
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundThe infiltration of CD8 T cells is usually linked to a favorable prognosis and may predict the therapeutic response of breast cancer patients to immunotherapy. The purpose of this research is to investigate the competing endogenous RNA (ceRNA) network correlated with the infiltration of CD8 T cells. MethodsBased on expression profiles, CD8 T cell abundances for each breast cancer (BC) patient were inferred using the bioinformatic method by immune markers and expression profiles. We were able to extract the differentially expressed RNAs (DEmRNAs, DEmiRNAs, and DElncRNAs) between low and high CD8 T-cell samples. The ceRNA network was constructed using Cytoscape. Machine learning models were built by lncRNAs to predict CD8 T-cell abundances. The lncRNAs were used to develop a prognostic model that could predict the survival rates of BC patients. The expression of selected lncRNA (XIST) was validated by quantitative real-time PCR (qRT-PCR). ResultsA total of 1,599 DElncRNAs, 89 DEmiRNAs, and 1,794 DEmRNAs between high and low CD8 T-cell groups were obtained. Two ceRNA networks that have positive or negative correlations with CD8 T cells were built. Among the two ceRNA networks, nine lncRNAs (MIR29B2CHG, NEAT1, MALAT1, LINC00943, LINC01146, AC092718.4, AC005332.4, NORAD, and XIST) were selected for model construction. Among six prevalent machine learning models, artificial neural networks performed best, with an area under the curve (AUC) of 0.855. Patients from the high-risk category with BC had a lower survival rate compared to those from the low-risk group. The qRT-PCR results revealed significantly reduced XIST expression in normal breast samples, which was consistent with our integrated analysis. ConclusionThese results potentially provide insights into the ceRNA networks linked with T-cell infiltration and provide accurate models for T-cell prediction.
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页数:9
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共 35 条
[1]   Current Landscape of Immunotherapy in Breast Cancer: A Review [J].
Adams, Sylvia ;
Gatti-Mays, Margaret E. ;
Kalinsky, Kevin ;
Korde, Larissa A. ;
Sharon, Elad ;
Amiri-Kordestani, Laleh ;
Bear, Harry ;
McArthur, Heather L. ;
Frank, Elizabeth ;
Perlmutter, Jane ;
Page, David B. ;
Vincent, Benjamin ;
Hayes, Jennifer F. ;
Gulley, James L. ;
Litton, Jennifer K. ;
Hortobagyi, Gabriel N. ;
Chia, Stephen ;
Krop, Ian ;
White, Julia ;
Sparano, Joseph ;
Disis, Mary L. ;
Mittendorf, Elizabeth A. .
JAMA ONCOLOGY, 2019, 5 (08) :1205-1214
[2]   Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression [J].
Becht, Etienne ;
Giraldo, Nicolas A. ;
Lacroix, Laetitia ;
Buttard, Benedicte ;
Elarouci, Nabila ;
Petitprez, Florent ;
Selves, Janick ;
Laurent-Puig, Pierre ;
Sautes-Fridman, Catherine ;
Fridman, Wolf H. ;
de Reynies, Aurelien .
GENOME BIOLOGY, 2016, 17
[3]   Pan-cancer Immunogenomic Analyses Reveal Genotype-Immunophenotype Relationships and Predictors of Response to Checkpoint Blockade [J].
Charoentong, Pornpimol ;
Finotello, Francesca ;
Angelova, Mihaela ;
Mayer, Clemens ;
Efremova, Mirjana ;
Rieder, Dietmar ;
Hackl, Hubert ;
Trajanoski, Zlatko .
CELL REPORTS, 2017, 18 (01) :248-262
[4]   A Machine Learning Model to Predict the Triple Negative Breast Cancer Immune Subtype [J].
Chen, Zihao ;
Wang, Maoli ;
De Wilde, Rudy Leon ;
Feng, Ruifa ;
Su, Mingqiang ;
Torres-de la Roche, Luz Angela ;
Shi, Wenjie .
FRONTIERS IN IMMUNOLOGY, 2021, 12
[5]   TCGAbiolinks: an R/Bioconductor package for integrative analysis of TCGA data [J].
Colaprico, Antonio ;
Silva, Tiago C. ;
Olsen, Catharina ;
Garofano, Luciano ;
Cava, Claudia ;
Garolini, Davide ;
Sabedot, Thais S. ;
Malta, Tathiane M. ;
Pagnotta, Stefano M. ;
Castiglioni, Isabella ;
Ceccarelli, Michele ;
Bontempi, Gianluca ;
Noushmehr, Houtan .
NUCLEIC ACIDS RESEARCH, 2016, 44 (08) :e71
[6]   Immune-related IncRNA LINC00944 responds to variations in ADAR1 levels and it is associated with breast cancer prognosis [J].
de Santiago, Pamela R. ;
Blanco, Alejandro ;
Morales, Fernanda ;
Marcelain, Katherine ;
Harismendy, Olivier ;
Herrera, Marcela Sjoberg ;
Armisen, Ricardo .
LIFE SCIENCES, 2021, 268
[7]   Tumor mutational burden quantification from targeted gene panels: major advancements and challenges [J].
Fancello, Laura ;
Gandini, Sara ;
Pelicci, Pier Giuseppe ;
Mazzarella, Luca .
JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7
[8]   Naturally-Occurring Canine Mammary Tumors as a Translational Model for Human Breast Cancer [J].
Gray, Mark ;
Meehan, James ;
Martinez-Perez, Carlos ;
Kay, Charlene ;
Turnbull, Arran K. ;
Morrison, Linda R. ;
Pang, Lisa Y. ;
Argyle, David .
FRONTIERS IN ONCOLOGY, 2020, 10
[9]   Xist reduction in breast cancer upregulates AKT phosphorylation via HDAC3-mediated repression of PHLPP1 expression [J].
Huang, Yen-Sung ;
Chang, Che-Chang ;
Lee, Szu-Shuo ;
Jou, Yuh-Shan ;
Shih, Hsiu-Ming .
ONCOTARGET, 2016, 7 (28) :43256-43266
[10]   ceRNA Cross-Talk in Cancer: When ce-bling Rivalries Go Awry [J].
Karreth, Florian A. ;
Pandolfi, Pier Paolo .
CANCER DISCOVERY, 2013, 3 (10) :1113-1121