Analysis of N6-methyladenosine-related lncRNAs in the tumor immune microenvironment and their prognostic role in pancreatic cancer

被引:1
作者
Liu, Yong [1 ]
Wang, Tao [2 ]
Fang, Ziqi [3 ]
Kong, Junjie [1 ,2 ]
Liu, Jun [1 ,2 ]
机构
[1] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Liver Transplantat & Hepatobiliary Surg, Jinan 250021, Shandong, Peoples R China
[2] Shandong First Med Univ, Shandong Prov Hosp, Dept Liver Transplantat & Hepatobiliary Surg, Jinan 250021, Shandong, Peoples R China
[3] Shandong Univ, Shandong Prov Hosp, Cheeloo Coll Med, Dept Clin Lab, Jinan 250021, Shandong, Peoples R China
基金
中国国家自然科学基金;
关键词
Pancreatic cancer; N6-methyladenosine; lncRNAs; Tumor immune microenvironment; Prognostic signature; MESSENGER-RNA; NONCODING RNAS; PROLIFERATION; IMMUNOTHERAPY; EXPRESSION; REGULATORS; PROMOTES; BURDEN; PURITY; GENE;
D O I
10.1007/s00432-022-03985-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background Pancreatic cancer (PC) is a rare solid malignancy with a poor prognosis. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in tumorigenesis and progression. However, little is known about the role of m6A-related lncRNAs in PC. Methods m6A-related lncRNAs were extracted by Pearson analysis, and then prognosis-related lncRNAs were filtered from the m6A-related lncRNAs by univariate Cox regression analysis. Based on the expression patterns of the prognosis-related lncRNAs, samples were classified into distinct clusters. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to construct a m6A-lncRNA-related prognostic signature for PC patients. Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC) values were used to evaluate the prognostic ability of the model. Results A total of 178 tumor and 4 normal samples were extracted from The Cancer Genome Atlas (TCGA) database in our study. Based on the expression of 12 filtered prognosis-related lncRNAs, two distinct clusters were eventually identified; these clusters were characterized by differences in the tumor immune microenvironment (TIME) and prognosis. A risk model comprising ten m6A-related lncRNAs was identified as an independent predictor of prognosis. ROC analysis revealed that this model had an acceptable prognostic value for PC patients. The prognostic signature was related to the TIME and the expression of critical immune checkpoint molecules. Conclusion This study comprehensively assessed the expression pattern and prognostic value of m6A-related lncRNAs in PC. The different clusters correlated with distinct TIMEs and prognoses. The study also constructed a ten-gene signature prognostic model based on m6A-related lncRNAs, which showed good accuracy in predicting overall survival.
引用
收藏
页码:1613 / 1626
页数:14
相关论文
共 55 条
[1]   Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study [J].
Ali, H. Raza ;
Chlon, Leon ;
Pharoah, Paul D. P. ;
Markowetz, Florian ;
Caldas, Carlos .
PLOS MEDICINE, 2016, 13 (12)
[2]   Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks [J].
Blanche, Paul ;
Dartigues, Jean-Francois ;
Jacqmin-Gadda, Helene .
STATISTICS IN MEDICINE, 2013, 32 (30) :5381-5397
[3]   The crosstalk between lncRNA and microRNA in cancer metastasis: orchestrating the epithelial-mesenchymal plasticity [J].
Cao, Ming-xin ;
Jiang, Ya-ping ;
Tang, Ya-ling ;
Liang, Xin-hua .
ONCOTARGET, 2017, 8 (07) :12472-12483
[4]   Metabolism within the tumor microenvironment and its implication on cancer progression: An ongoing therapeutic target [J].
Carmen Ocana, Ma ;
Martinez-Poveda, Beatriz ;
Quesada, Ana R. ;
Angel Medina, Miguel .
MEDICINAL RESEARCH REVIEWS, 2019, 39 (01) :70-113
[5]   m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells [J].
Cui, Qi ;
Shi, Hailing ;
Ye, Peng ;
Li, Li ;
Qu, Qiuhao ;
Sun, Guoqiang ;
Sun, Guihua ;
Lu, Zhike ;
Huang, Yue ;
Yang, Cai-Guang ;
Riggs, Arthur D. ;
He, Chuan ;
Shi, Yanhong .
CELL REPORTS, 2017, 18 (11) :2622-2634
[6]   IDENTIFICATION OF METHYLATED NUCLEOSIDES IN MESSENGER-RNA FROM NOVIKOFF HEPATOMA-CELLS [J].
DESROSIERS, R ;
FRIDERICI, K ;
ROTTMAN, F .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1974, 71 (10) :3971-3975
[7]   The Pancreatic Cancer Microenvironment [J].
Dougan, Stephanie K. .
CANCER JOURNAL, 2017, 23 (06) :321-325
[8]   METHYLATION STATE OF POLY A-CONTAINING MESSENGER RNA FROM CULTURED HAMSTER CELLS [J].
DUBIN, DT ;
TAYLOR, RH .
NUCLEIC ACIDS RESEARCH, 1975, 2 (10) :1653-1668
[9]   PD-1/PD-L1 and immunotherapy for pancreatic cancer [J].
Feng, Mengyu ;
Xiong, Guangbing ;
Cao, Zhe ;
Yang, Gang ;
Zheng, Suli ;
Song, Xujun ;
You, Lei ;
Zheng, Lianfang ;
Zhang, Taiping ;
Zhao, Yupei .
CANCER LETTERS, 2017, 407 :57-65
[10]   Preoperative/Neoadjuvant Therapy in Pancreatic Cancer: A Systematic Review and Meta-analysis of Response and Resection Percentages [J].
Gillen, Sonja ;
Schuster, Tibor ;
zum Bueschenfelde, Christian Meyer ;
Friess, Helmut ;
Kleeff, Joerg .
PLOS MEDICINE, 2010, 7 (04)