A novel stemness classification in acute myeloid leukemia by the stemness index and the identification of cancer stem cell-related biomarkers

被引:7
作者
Huang, Yue [1 ]
Zhang, Zhuo [2 ,3 ]
Sui, Meijuan [4 ]
Li, Yang [5 ]
Hu, Yi [6 ]
Zhang, Haiyu [7 ]
Zhang, Fan [2 ]
机构
[1] Harbin Med Univ, Sch Publ Hlth, Dept Biostat, Harbin, Peoples R China
[2] Harbin Med Univ, Natl Hlth Commiss NHC Key Lab Cell Transplantat, Affiliated Hosp 1, Harbin, Peoples R China
[3] Southern Univ Sci & Technol Hosp, Dept Hematol, Shenzhen, Peoples R China
[4] Harbin Med Univ, Key Lab Hepatosplen Surg, Minist Educ, Affiliated Hosp 1, Harbin, Peoples R China
[5] Harbin Med Univ, Med Insurance Off, Affiliated Hosp 1, Harbin, Peoples R China
[6] Harbin Inst Technol, Fac Comp, Ctr Bioinformat, Harbin, Heilongjiang, Peoples R China
[7] Harbin Med Univ, Key Lab Cardiovasc Dis Acousto Opt Electromagnet D, Affiliated Hosp 1, Harbin, Peoples R China
基金
中国国家自然科学基金;
关键词
AML; cancer stem cell; mRNAsi; biomarkers; MUTATIONS; SUBPOPULATION; INHIBITION; RELEVANCE; AXITINIB; EFFICACY; SUBSETS; BIOLOGY;
D O I
10.3389/fimmu.2023.1202825
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundStem cells play an important role in acute myeloid leukemia (AML). However, their precise effect on AML tumorigenesis and progression remains unclear. MethodsThe present study aimed to characterize stem cell-related gene expression and identify stemness biomarker genes in AML. We calculated the stemness index (mRNAsi) based on transcription data using the one-class logistic regression (OCLR) algorithm for patients in the training set. According to the mRNAsi score, we performed consensus clustering and identified two stemness subgroups. Eight stemness-related genes were identified as stemness biomarkers through gene selection by three machine learning methods. ResultsWe found that patients in stemness subgroup I had a poor prognosis and benefited from nilotinib, MK-2206 and axitinib treatment. In addition, the mutation profiles of these two stemness subgroups were different, which suggested that patients in different subgroups had different biological processes. There was a strong significant negative correlation between mRNAsi and the immune score (r= -0.43, p<0.001). Furthermore, we identified eight stemness-related genes that have potential to be biomarkers, including SLC43A2, CYBB, CFP, GRN, CST3, TIMP1, CFD and IGLL1. These genes, except IGLL1, had a negative correlation with mRNAsi. SLC43A2 is expected to be a potential stemness-related biomarker in AML. ConclusionOverall, we established a novel stemness classification using the mRNAsi score and eight stemness-related genes that may be biomarkers. Clinical decision-making should be guided by this new signature in prospective studies.
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页数:11
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共 53 条
[1]   Prospective identification of tumorigenic breast cancer cells [J].
Al-Hajj, M ;
Wicha, MS ;
Benito-Hernandez, A ;
Morrison, SJ ;
Clarke, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :3983-3988
[2]   Cancer SLC43A2 alters T cell methionine metabolism and histone methylation [J].
Bian, Yingjie ;
Li, Wei ;
Kremer, Daniel M. ;
Sajjakulnukit, Peter ;
Li, Shasha ;
Crespo, Joel ;
Nwosu, Zeribe C. ;
Zhang, Li ;
Czerwonka, Arkadiusz ;
Pawlowska, Anna ;
Xia, Houjun ;
Li, Jing ;
Liao, Peng ;
Yu, Jiali ;
Vatan, Linda ;
Szeliga, Wojciech ;
Wei, Shuang ;
Grove, Sara ;
Liu, J. Rebecca ;
McLean, Karen ;
Cieslik, Marcin ;
Chinnaiyan, Arul M. ;
Zgodzinski, Witold ;
Wallner, Grzegorz ;
Wertel, Iwona ;
Okla, Karolina ;
Kryczek, Ilona ;
Lyssiotis, Costas A. ;
Zou, Weiping .
NATURE, 2020, 585 (7824) :277-+
[3]   Survivin is highly expressed in CD34+38- leukemic stem/progenitor cells and predicts poor clinical outcomes in AML [J].
Carter, Bing Z. ;
Qiu, Yihua ;
Huang, Xuelin ;
Diao, Lixia ;
Zhang, Nianxiang ;
Coombes, Kevin R. ;
Mak, Duncan H. ;
Konopleva, Marina ;
Cortes, Jorge ;
Kantarjian, Hagop M. ;
Mills, Gordon B. ;
Andreeff, Michael ;
Kornblau, Steven M. .
BLOOD, 2012, 120 (01) :173-180
[4]   Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells [J].
Chan, Keith Syson ;
Espinosa, Inigo ;
Chao, Mark ;
Wong, David ;
Ailles, Laurie ;
Diehn, Max ;
Gill, Harcharan ;
Presti, Joseph, Jr. ;
Chang, Howard Y. ;
van de Rijn, Matt ;
Shortliffe, Linda ;
Weissman, Irving L. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (33) :14016-14021
[5]   Cancer Stem Cell Quiescence and Plasticity as Major Challenges in Cancer Therapy [J].
Chen, Wanyin ;
Dong, Jihu ;
Haiech, Jacques ;
Kilhoffer, Marie-Claude ;
Zeniou, Maria .
STEM CELLS INTERNATIONAL, 2016, 2016
[6]   Prospective identification of tumorigenic prostate cancer stem cells [J].
Collins, AT ;
Berry, PA ;
Hyde, C ;
Stower, MJ ;
Maitland, NJ .
CANCER RESEARCH, 2005, 65 (23) :10946-10951
[7]   Phenotypic characterization of human colorectal cancer stem cells [J].
Dalerba, Piero ;
Dylla, Scott J. ;
Park, In-Kyung ;
Liu, Rui ;
Wang, Xinhao ;
Cho, Robert W. ;
Hoey, Timothy ;
Gurney, Austin ;
Huang, Emina H. ;
Simeone, Diane M. ;
Shelton, Andrew A. ;
Parmiani, Giorgio ;
Castelli, Chiara ;
Clarke, Michael F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (24) :10158-10163
[8]   Acute myeloid leukemia: a comprehensive review and 2016 update [J].
De Kouchkovsky, I. ;
Abdul-Hay, M. .
BLOOD CANCER JOURNAL, 2016, 6 :e441-e441
[9]   Stem cell gene expression programs influence clinical outcome in human leukemia [J].
Eppert, Kolja ;
Takenaka, Katsuto ;
Lechman, Eric R. ;
Waldron, Levi ;
Nilsson, Bjoern ;
van Galen, Peter ;
Metzeler, Klaus H. ;
Poeppl, Armando ;
Ling, Vicki ;
Beyene, Joseph ;
Canty, Angelo J. ;
Danska, Jayne S. ;
Bohlander, Stefan K. ;
Buske, Christian ;
Minden, Mark D. ;
Golub, Todd R. ;
Jurisica, Igor ;
Ebert, Benjamin L. ;
Dick, John E. .
NATURE MEDICINE, 2011, 17 (09) :1086-U91
[10]   Identification and expansion of the tumorigenic lung cancer stem cell population [J].
Eramo, A. ;
Lotti, F. ;
Sette, G. ;
Pilozzi, E. ;
Biffoni, M. ;
Di Virgilio, A. ;
Conticello, C. ;
Ruco, L. ;
Peschle, C. ;
De Maria, R. .
CELL DEATH AND DIFFERENTIATION, 2008, 15 (03) :504-514