PUM1 is upregulated by DNA methylation to suppress antitumor immunity and results in poor prognosis in pancreatic cancer

被引:9
作者
Yang, Yishi [1 ]
Su, Xingxing [1 ]
Shen, Kaicheng [1 ]
Zhang, Chengcheng [1 ]
Dai, Haisu [1 ]
Ma, Hongbo [2 ]
Jiang, Yan [1 ]
Shuai, Ling [1 ]
Liu, Zhipeng [1 ]
You, Jinshan [1 ]
Min, Ke [1 ]
Chen, Zhiyu [1 ]
机构
[1] Army Med Univ, Affiliated Hosp 1, Southwest Hosp, Dept Hepatobiliary Surg, Chongqing, Peoples R China
[2] Fuling Cent Hosp Chongqing City, Dept Oncol, Chongqing, Peoples R China
基金
中国国家自然科学基金;
关键词
Pumilio homologous protein 1 (PUM1); pancreatic cancer; tumor biomarkers; tumor immune microenvironment; bioinformatics; CARBOHYDRATE ANTIGEN 19-9; MISMATCH REPAIR DEFICIENCY; RNA-BINDING PROTEINS; DIFFERENTIAL-DIAGNOSIS; TUMOR MICROENVIRONMENT; COLORECTAL-CANCER; EXPRESSION; GENES; BENIGN; HYPOMETHYLATION;
D O I
10.21037/tcr-20-3295
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Pancreatic carcinoma (PAAD) is a highly malignant cancer with a poor prognosis and high mortality rate. Pumilio homologous protein 1 (PUM1) promotes cell growth, invasion, and metastasis and suppresses apoptosis in many different kinds of cancers, such as non-small-cell lung carcinoma (NSCLC), ovarian cancer and lymphocyte leukemia. However, the underlying mechanism and potential role of PUM1 in PAAD have not been investigated. Methods: Bioinformatics analysis was performed using multiple databases [The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), BBCancer, Human Protein Atlas (HPA), MethSurv, cBioPortal, The Cancer Imaging Archive (TCIA), xCell, Gene Expression Omnibus (GEO)] to explore the diagnostic and prognostic role of PUM1, and the relationship between expression of PUM1 and prognosis of patients with PAAD. The analysis was further validated using the Kaplan-Meier plotter. Results: PUM1 plays a role in both diagnostic and prognostic prediction. The PUM1 mRNA expression level correlates with both the prognosis and incidence of pancreatic cancer. PUM1 can serve as a potential diagnostic indicator for pancreatic cancer. Furthermore, the DNA methylation levels of PUM1 affects its oncogene function in pancreatic cancer. PUM1 can also inhibit the immune microenvironment by altering immune cell infiltration, which affects immunotherapy response in pancreatic cancer. Conclusions: PUM1 takes a crucial part in the immune microenvironment and immunotherapy response of PAAD and is potentially useful for the development of novel diagnostic and treatment strategies.
引用
收藏
页码:2153 / +
页数:17
相关论文
共 65 条
  • [41] Therapeutic developments in pancreatic cancer: current and future perspectives
    Neoptolemos, John P.
    Kleeff, Joerg
    Michl, Patrick
    Costello, Eithne
    Greenhalf, William
    Palmer, Daniel H.
    [J]. NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2018, 15 (06) : 332 - 347
  • [42] Novik K. L., 2002, Current Issues in Molecular Biology, V4, P111
  • [43] Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors
    Rawla, Prashanth
    Sunkara, Tagore
    Gaduputi, Vinaya
    [J]. WORLD JOURNAL OF ONCOLOGY, 2019, 10 (01) : 10 - 27
  • [44] Nivolumab in Previously Untreated Melanoma without BRAF Mutation
    Robert, Caroline
    Long, Georgina V.
    Brady, Benjamin
    Dutriaux, Caroline
    Maio, Michele
    Mortier, Laurent
    Hassel, Jessica C.
    Rutkowski, Piotr
    McNeil, Catriona
    Kalinka-Warzocha, Ewa
    Savage, Kerry J.
    Hernberg, Micaela M.
    Lebbe, Celeste
    Charles, Julie
    Mihalcioiu, Catalin
    Chiarion-Sileni, Vanna
    Mauch, Cornelia
    Cognetti, Francesco
    Arance, Ana
    Schmidt, Henrik
    Schadendorf, Dirk
    Gogas, Helen
    Lundgren-Eriksson, Lotta
    Horak, Christine
    Sharkey, Brian
    Waxman, Ian M.
    Atkinson, Victoria
    Ascierto, Paolo A.
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) : 320 - 330
  • [45] Serum tumor markers and molecular biological diagnosis in pancreatic cancer
    Sawabu, N
    Watanabe, H
    Yamaguchi, Y
    Ohtsubo, K
    Motoo, Y
    [J]. PANCREAS, 2004, 28 (03) : 263 - 267
  • [46] Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures
    Senbabaoglu, Yasin
    Gejman, Ron S.
    Winer, Andrew G.
    Liu, Ming
    Van Allen, Eliezer M.
    de Velasco, Guillermo
    Miao, Diana
    Ostrovnaya, Irina
    Drill, Esther
    Luna, Augustin
    Weinhold, Nils
    Lee, William
    Manley, Brandon J.
    Khalil, Danny N.
    Kaffenberger, Samuel D.
    Chen, Yingbei
    Danilova, Ludmila
    Voss, Martin H.
    Coleman, Jonathan A.
    Russo, Paul
    Reuter, Victor E.
    Chan, Timothy A.
    Cheng, Emily H.
    Scheinberg, David A.
    Li, Ming O.
    Choueiri, Toni K.
    Hsieh, James J.
    Sander, Chris
    Hakimi, A. Ari
    [J]. GENOME BIOLOGY, 2016, 17
  • [47] Pancreatic Cancer Screening
    Shin, Eun Ji
    Canto, Marcia Irene
    [J]. GASTROENTEROLOGY CLINICS OF NORTH AMERICA, 2012, 41 (01) : 143 - +
  • [48] Combined hereditary and somatic mutations of replication error repair genes result in rapid onset of ultra-hypermutated cancers
    Shlien, Adam
    Campbell, Brittany B.
    de Borja, Richard
    Alexandrov, Ludmil B.
    Merico, Daniele
    Wedge, David
    Van Loo, Peter
    Tarpey, Patrick S.
    Coupland, Paul
    Behjati, Sam
    Pollett, Aaron
    Lipman, Tatiana
    Heidari, Abolfazl
    Deshmukh, Shriya
    Avitzur, Na'ama
    Meier, Bettina
    Gerstung, Moritz
    Hong, Ye
    Merino, Diana M.
    Ramakrishna, Manasa
    Remke, Marc
    Arnold, Roland
    Panigrahi, Gagan B.
    Thakkar, Neha P.
    Hodel, Karl P.
    Henninger, Erin E.
    Goeksenin, A. Yasemin
    Bakry, Doua
    Charames, George S.
    Druker, Harriet
    Lerner-Ellis, Jordan
    Mistry, Matthew
    Dvir, Rina
    Grant, Ronald
    Elhasid, Ronit
    Farah, Roula
    Taylor, Glenn P.
    Nathan, Paul C.
    Alexander, Sarah
    Ben-Shachar, Shay
    Ling, Simon C.
    Gallinger, Steven
    Constantini, Shlomi
    Dirks, Peter
    Huang, Annie
    Scherer, Stephen W.
    Grundy, Richard G.
    Durno, Carol
    Aronson, Melyssa
    Gartner, Anton
    [J]. NATURE GENETICS, 2015, 47 (03) : 257 - +
  • [49] The PUF family of RNA-binding proteins: Does evolutionarily conserved structure equal conserved function?
    Spassov, DS
    Jurecic, R
    [J]. IUBMB LIFE, 2003, 55 (07) : 359 - 366
  • [50] Cloning and comparative sequence analysis of PUM1 and PUM2 genes, human members of the Pumilio family of RNA-binding proteins
    Spassov, DS
    Jurecic, R
    [J]. GENE, 2002, 299 (1-2) : 195 - 204